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Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis.

Background: Several interventions are available for management of obsessive-compulsive disorder in adults, but few studies have compared their relative efficacy in a single analysis. We aimed to simultaneously compare all available treatments using both direct and indirect data. Methods: In this systematic review and network meta-analysis, we searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group for trials published up to Feb 16, 2016. We selected randomised controlled trials in which an active psychotherapeutic or pharmacological intervention had been used in adults with obsessive-compulsive disorder. We allowed all comorbidities except for schizophrenia or bipolar disorder. We excluded studies that focused exclusively on treatment-resistant patient populations defined within the same study. We extracted data from published reports. The primary outcome was symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale. We report mean differences with 95% credible intervals compared with placebo. This study is registered with PROSPERO, number CRD42012002441. Findings: We identified 1480 articles in our search and included 53 articles (54 trials; 6652 participants) in the network meta-analysis. Behavioural therapy (mean difference -14·48 [95% credible interval -18·61 to -10·23]; 11 trials and 287 patients), cognitive therapy (-13·36 [-18·40 to -8·21]; six trials and 172 patients), behavioural therapy and clomipramine (-12·97 [-19·18 to -6·74]; one trial and 31 patients), cognitive behavioural therapy and fluvoxamine (-7·50 [-13·89 to -1·17]; one trial and six patients), cognitive behavioural therapy (-5·37 [-9·10 to -1·63]; nine trials and 231 patients), clomipramine (-4·72 [-6·85 to -2·60]; 13 trials and 831 patients), and all SSRIs (class effect -3·49 [95% credible interval -5·12 to -1·81]; 37 trials and 3158 patients) had greater effects than did drug placebo. Clomipramine was not better than were SSRIs (-1·23 [-3·41 to 0·94]). Psychotherapeutic interventions had a greater effect than did medications, but a serious limitation was that most psychotherapeutic trials included patients who were taking stable doses of antidepressants (12 [80%] of the 15 psychotherapy trials explicitly allowed antidepressants). Interpretation: A range of interventions is effective in the management of obsessive-compulsive disorder, but considerable uncertainty and limitations exist regarding their relative efficacy. Taking all the evidence into account, the combination of psychotherapeutic and psychopharmacological interventions is likely to be more effective than are psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder. Funding: National Institute for Health Research.

The lancet. Psychiatry · systematic review · 236 citationsread the source →

Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-on Treatment for Bipolar Depression: A Randomized Clinical Trial.

Importance: More effective, tolerable interventions for bipolar depression treatment are needed. Transcranial direct current stimulation (tDCS) is a novel therapeutic modality with few severe adverse events that showed promising results for unipolar depression. Objective: To determine the efficacy and safety of tDCS as an add-on treatment for bipolar depression. Design, setting, and participants: A randomized, sham-controlled, double-blind trial (the Bipolar Depression Electrical Treatment Trial [BETTER]) was conducted from July 1, 2014, to March 30, 2016, at an outpatient, single-center academic setting. Participants included 59 adults with type I or II bipolar disorder in a major depressive episode and receiving a stable pharmacologic regimen with 17-item Hamilton Depression Rating Scale (HDRS-17) scores higher than 17. Data were analyzed in the intention-to-treat sample. Interventions: Ten daily 30-minute, 2-mA, anodal-left and cathodal-right prefrontal sessions of active or sham tDCS on weekdays and then 1 session every fortnight until week 6. Main outcomes and measures: Change in HDRS-17 scores at week 6. Results: Fifty-nine patients (40 [68%] women), with a mean (SD) age of 45.9 (12) years participated; 36 (61%) with bipolar I and 23 (39%) with bipolar II disorder were randomized and 52 finished the trial. In the intention-to-treat analysis, patients in the active tDCS condition showed significantly superior improvement compared with those receiving sham (βint = -1.68; number needed to treat, 5.8; 95% CI, 3.3-25.8; P = .01). Cumulative response rates were higher in the active vs sham groups (67.6% vs 30.4%; number needed to treat, 2.69; 95% CI, 1.84-4.99; P = .01), but not remission rates (37.4% vs 19.1%; number needed to treat, 5.46; 95% CI, 3.38-14.2; P = .18). Adverse events, including treatment-emergent affective switches, were similar between groups, except for localized skin redness that was higher in the active group (54% vs 19%; P = .01). Conclusions and relevance: In this trial, tDCS was an effective, safe, and tolerable add-on intervention for this small bipolar depression sample. Further trials should examine tDCS efficacy in a larger sample. Trial registration: clinicaltrials.gov Identifier: NCT02152878.

JAMA psychiatry · randomised controlled trial · 103 citationsread the source →

Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study.

Background: Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety. Methods: In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in eight countries and enrolled within 16 h of presentation. Patients were randomly assigned, in a double-blind manner via a telephone-based interactive voice response system, to standard care plus 48-h intravenous infusion of placebo (n=62) or relaxin 10 microg/kg (n=40), 30 microg/kg (n=43), 100 microg/kg (n=39), or 250 microg/kg (n=50) per day. Several clinical endpoints were explored to assess whether intravenous relaxin should be pursued in larger studies of acute heart failure, to identify an optimum dose, and to help to assess endpoint selection and power calculations. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00520806. Findings: In the modified intention-to-treat population, 61 patients were assessed in the placebo group, 40 in the relaxin 10 microg/kg per day group, 42 in the relaxin 30 microg/kg per day group, 37 in the relaxin 100 microg/kg per day group, and 49 in the relaxin 250 microg/kg per day group. Dyspnoea improved with relaxin 30 microg/kg compared with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0.044) and visual analogue scale through day 14 (8214 mm x h [SD 8712] vs 4622 mm x h [9003]; p=0.053). Length of stay was 10.2 days (SD 6.1) for relaxin-treated patients versus 12.0 days (7.3) for those given placebo, and days alive out of hospital were 47.9 (10.1) versus 44.2 (14.2). Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced with relaxin (2.6% [95% CI 0.4-16.8] vs 17.2% [9.6-29.6]; p=0.053). The number of serious adverse events was similar between groups. Interpretation: When given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favourable relief of dyspnoea and other clinical outcomes, with acceptable safety.

Lancet (London, England) · randomised controlled trial · 314 citationsread the source →

Developing a multidisciplinary rehabilitation package following hip fracture and testing in a randomised feasibility study: Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR).

Background: Proximal femoral fracture is a major health problem in old age, with annual UK health and social care costs of £2.3B. Rehabilitation has the potential to maximise functional recovery and maintain independent living, but evidence of clinical effectiveness and cost-effectiveness is lacking. Objectives: To develop an enhanced community-based rehabilitation package following surgical treatment for proximal femoral fracture and to assess acceptability and feasibility for a future definitive randomised controlled trial (RCT) and economic evaluation. Design: Phase I - realist review, survey and focus groups to develop the rehabilitation package. Phase II - parallel-group, randomised (using a dynamic adaptive algorithm) feasibility study with focus groups and an anonymised cohort study. Setting: Recruitment was from orthopaedic wards of three acute hospitals in the Betsi Cadwaladr University Health Board, North Wales. The intervention was delivered in the community following hospital discharge. Participants: Older adults (aged ≥ 65 years) who had received surgical treatment for hip fracture, lived independently prior to fracture, had mental capacity (assessed by the clinical team) and received rehabilitation in the North Wales area. Interventions: Participants received usual care (control) or usual care plus an enhanced rehabilitation package (intervention). Usual care was variable and consisted of multidisciplinary rehabilitation delivered by the acute hospital, community hospital and community services depending on need and availability. The intervention was designed to enhance rehabilitation by improving patients' self-efficacy and increasing the amount and quality of patients' practice of physical exercise and activities of daily living. It consisted of a patient-held information workbook, a goal-setting diary and six additional therapy sessions. Main outcome measures: The primary outcome measure was the Barthel Activities of Daily Living (BADL) index. The secondary outcome measures included the Nottingham Extended Activities of Daily Living (NEADL) scale, EuroQol-5 Dimensions, ICEpop CAPability measure for Older people, General Self-Efficacy Scale, Falls Efficacy Scale - International (FES-I), Self-Efficacy for Exercise scale, Hospital Anxiety and Depression Scale (HADS) and service use measures. Outcome measures were assessed at baseline and at 3-month follow-up by blinded researchers. Results: Sixty-two participants were recruited (23% of those who were eligible), 61 were randomised (control, n = 32; intervention, n = 29) and 49 (79%) were followed up at 3 months. Compared with the cohort study, a younger, healthier subpopulation was recruited. There were minimal differences in most outcomes between the two groups, including the BADL index, with an adjusted mean difference of 0.5 (Cohen's d = 0.29). The intervention group showed a medium-sized improvement on the NEADL scale relative to the control group, with an adjusted mean difference between groups of 3.0 (Cohen's d = 0.63). There was a trend for greater improvement in FES-I and HADS in the intervention group, but with small effect sizes, with an adjusted mean difference of 4.2 (Cohen's d = 0.31) and 1.3 (Cohen's d = 0.20), respectively. The cost of delivering the intervention was £231 per patient. There was a possible small relative increase in quality-adjusted life-years in the intervention group. No serious adverse events relating to the intervention were reported. Conclusions: Trial methods were feasible in terms of eligibility, recruitment and retention, although recruitment was challenging. The NEADL scale was more responsive than the BADL index, suggesting that the intervention could enable participants to regain better levels of independence compared with usual care. This should be tested in a definitive Phase III RCT. There were two main limitations of the study: the feasibility study lacked power to test for differences between the groups and a ceiling effect was observed in the primary measure. Trial registration: Current Controlled Trials ISRCTN22464643. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 44. See the NIHR Journals Library for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 17 citationsread the source →

Effectiveness of a school-based group psychotherapy program for war-exposed adolescents: a randomized controlled trial.

Objective: To evaluate the comparative effectiveness of a classroom-based psychoeducation and skills intervention (tier 1) and a school-based trauma- and grief-focused group treatment (tier 2) of a three-tiered mental health program for adolescents exposed to severe war-related trauma, traumatic bereavement, and postwar adversity. Method: A total of 127 war-exposed and predominantly ethnic Muslim secondary school students attending 10 schools in central Bosnia who reported severe symptoms of posttraumatic stress disorder (PTSD), depression, or maladaptive grief and significant impairment in school or relationships were randomly assigned to one of two experimental conditions. These included either an active-treatment comparison condition (tier 1), consisting of a classroom-based psychoeducation and skills intervention alone (n = 61, 66% girls, mean age 16.0 years, SD 1.13) or a treatment condition composed of both the classroom-based intervention and a 17-session manual-based group therapy intervention (tier 2), trauma and grief component therapy for adolescents (n = 66, 63% girls, mean age 15.9 years, SD 1.11). Both interventions were implemented throughout the school year. Distressed students who were excluded from the study due to acute risk for harm (n = 9) were referred for community-based mental health services (tier 3). Results: Program effectiveness was measured via reductions in symptoms of PTSD, depression, and maladaptive grief assessed at pretreatment, posttreatment, and 4-month follow-up. Analysis of mean-level treatment effects showed significant pre- to posttreatment and posttreatment to 4-month follow-up reductions in PTSD and depression symptoms in both the treatment and comparison conditions. Significant pre- to posttreatment reductions in maladaptive grief reactions were found only in the treatment condition. Analyzed at the individual case level, the percentages of students in the treatment condition who reported significant (p <.05) pre- to posttreatment reductions in PTSD symptoms (58% at posttreatment, 81% at 4-month follow-up) compare favorably to those reported in controlled treatment efficacy trials, whereas the percentages who reported significant reductions in depression symptoms (23% at posttreatment, 61% at follow-up) are comparable to, or higher than, those found in community treatment settings. Lower but substantial percentages of significant symptom reduction were found for PTSD (33% at posttreatment, 48% at follow-up) and depression symptoms (13% at posttreatment; 47% at follow-up) in students in the comparison condition. The odds of significant symptom reduction were higher for PTSD symptoms at both posttreatment and 4-month follow-up and for maladaptive grief at posttreatment (no follow-up was conducted on maladaptive grief). Rates of significantly worsened cases were generally rare in both the treatment and comparison conditions. Conclusions: A three-tiered, integrative mental health program composed of schoolwide dissemination of psychoeducation and coping skills (tier 1), specialized trauma- and grief-focused intervention for severely traumatized and traumatically bereaved youths (tier 2), and referral of youths at acute risk for community-based mental health services (tier 3) constitutes an effective and efficient method for promoting adolescent recovery in postwar settings.

Journal of the American Academy of Child and Adolescent Psychiatry · randomised controlled trial · 141 citationsread the source →

Methylphenidate and the risk of psychosis in adolescents and young adults: a population-based cohort study.

Background: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder. Methods: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis. Findings: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38·7%) individuals were assessed and 37 916 (61·3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2·0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80-1·34) in adolescents and young adults without a history of psychosis and 0·95 (0·69-1·30) among those with a history of psychosis. Interpretation: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis. Funding: Swedish Research Council, National Institute of Mental Health, UK National Institute of Health Research Nottingham Biomedical Research Centre.

The lancet. Psychiatry · cohort or longitudinal · 45 citationsread the source →

Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis.

Background: Understanding patterns of relapse in patients who respond to antidepressant treatment can inform strategies for prevention of relapse. We aimed to identify distinct trajectories of depression severity, assess whether similar or different trajectory classes exist for patients who continued or discontinued active treatment, and test whether clinical predictors of trajectory class membership exist using pooled data from clinical trials. Methods: We analysed individual patient data from four double-blind discontinuation clinical trials of duloxetine or fluoxetine versus placebo in major depression from before 2012 (n=1462). We modelled trajectories of relapse up to 26 weeks during double-blind treatment. Trajectories of depression severity, as measured by the Hamilton Depression Rating Scale score, were identified in the entire sample, and separately in groups in which antidepressants had been continued or discontinued, using growth mixture models. Predictors of trajectory class membership were assessed with weighted logistic regression. Findings: We identified similar relapse trajectories and two trajectories of stable depression scores in the normal range on active medication and on placebo. Active treatment significantly lowered the odds of membership in the relapse trajectory (odds ratio 0·47, 95% CI 0·37-0·61), whereas female sex (1·56, 1·23-2·06), shorter length of time with clinical response by 1 week (1·10, 1·06-1·15), and higher Clinical Global Impression score at baseline (1·28, 1·01-1·62) increased the odds. Overall, the protective effect of antidepressant medication relative to placebo on the risk of being classified as a relapser was about 13% (33% vs 46%). Interpretation: The existence of similar relapse trajectories on active medication and on placebo suggests that there is no specific relapse signature associated with antidepressant discontinuation. Furthermore, continued treatment offers only modest protection against relapse. These data highlight the need to incorporate treatment strategies that prevent relapse as part of the treatment of depression. Funding: National Institutes of Health, the US Department of Veterans Affairs Alcohol Research Center, and National Center for Post-Traumatic Stress Disorder.

The lancet. Psychiatry · randomised controlled trial · 49 citationsread the source →

Three-year follow-up of same-sex couples who had civil unions in Vermont, same-sex couples not in civil unions, and heterosexual married couples.

This study was a 3-year follow-up of 65 male and 138 female same-sex couples who had civil unions in Vermont during the 1st year of that legislation. These couples were compared with 23 male and 61 female same-sex couples in their friendship circles who did not have civil unions and with 55 heterosexual married couples (1 member of each was a sibling to a member of a civil union couple). Despite the legalized nature of their relationships, civil union couples did not differ on any measure from same-sex couples who were not in civil unions. However, same-sex couples not in civil unions were more likely to have ended their relationships than same-sex civil union or heterosexual married couples. Compared with heterosexual married participants, both types of same-sex couples reported greater relationship quality, compatibility, and intimacy and lower levels of conflict. Longitudinal predictors of relationship quality at Time 2 included less conflict, greater level of outness, and a shorter relationship length for men in same-sex relationships and included less conflict and more frequent sex for women in same-sex relationships at Time 1.

Developmental psychology · cohort or longitudinal · 50 citationsread the source →

Effect of Ramadan diurnal fasting on visceral adiposity and serum adipokines in overweight and obese individuals.

Aim: Excessive visceral adiposity is a major risk factor for developing insulin resistance and systemic low-grade inflammation. Ramadan diurnal fasting (RDF) is a religious ritual practiced by more than one billion Muslim throughout the world. It has been considered as one of the most common types of complementary and integrative health practices. The aim of this study is to examine the impact of RDF on visceral adiposity, circulating adipokines and glucoregulatory markers in patients with overweight or obesity. Methods: Overweight and obese subjects (n = 61; 23 men and 38 women) were included in the study. Body weight, visceral fat tissue area (measured by 3D-MRI), glucoregulatory factors, serum adipokines concentrations, dietary intake, and physical activity were assessed one week before and at the end of the lunar month of Ramadan. Results: From baseline, body weight and visceral fat tissue area serum total cholesterol, triglycerides, HDL-cholesterol, and systolic blood pressure significantly decreased (P < 0.05 for each) at the end of Ramadan. The serum levels of adiponectin, IL-6, TNF-α, and IGF-1 significantly decreased (P < 0.05 for each), but serum visfatin, leptin, apelin, IL-10, and IL-10/IL-6 ratio significantly increased (P < 0.05 for each) at the end of Ramadan. Changes in visceral adiposity significantly correlated with changes in plasma glucose (r = 0.4, P < 0.5) and resistin (r = 0.44, P < 0.001) at the end of Ramadan. Conclusion: RDF lowers visceral adiposity, body weight and variably affects adipokines without adversely affecting markers of glucose homeostasis in individuals with overweight or obesity.

Diabetes research and clinical practice · 63 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials.

Background: The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes. Methods: We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy. Findings: Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction. Interpretation: Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials. Funding: Foundation for National Institutes of Health.

The lancet. Diabetes & endocrinology · systematic review · 165 citationsread the source →

Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster randomised trial.

Background: Parenting interventions have been implemented to improve the compromised developmental potential among 39% of children younger than 5 years living in low-income and middle-income countries. Maternal wellbeing is important for child development, especially in children younger than 3 years who are vulnerable and dependent on their mothers for nutrition and stimulation. We assessed an integrated, community-based parenting intervention that targeted both child development and maternal wellbeing in rural Uganda. Methods: In this community-based, cluster randomised trial, we assessed the effectiveness of a manualised, parenting intervention in Lira, Uganda. We selected and randomly assigned 12 parishes (1:1) to either parenting intervention or control (inclusion on a waitlist with a brief message on nutrition) groups using a computer-generated list of random numbers. Within each parish, we selected two to three eligible communities that had a parish office or a primary school in which a preschool could be established, more than 75 households with children younger than 6 years, and at least 15 socially disadvantaged families (ie, maternal education of primary school level or lower) with at least one child younger than 36 months. Participants within communities were mother-child dyads, where the child was 12-36 months of age at enrollment, and the mother had low maternal education. In the parenting intervention group, participants attended 12 fortnightly peer-led group sessions focusing on child care and maternal wellbeing. The primary outcomes were cognitive and receptive language development, as measured with the Bayley Scales of Infant Development, 3rd edn. Secondary outcomes included self-reported maternal depressive symptoms, using the Center for Epidemiologic Studies Depression Scale, and child growth. Theoretically-relevant parenting practices, including the Home Observation for Measurement of the Environment inventory, and mother-care variables, such as perceived spousal support, were also assessed as potential mediators. Baseline assessments were done in January, 2013, and endline assessments were done in November, 2013, 3 months after completion of the programme. Ethics approval was received from Mbarara and McGill universities. This trial is registered with ClinicalTrials.gov, NCT01906606. Findings: Between December, 2012, and January, 2013, 13 communities (194 dyads) were randomly assigned to receive intervention, and 12 communities (154 dyads) were assigned to a waitlist control. 319 dyads completed baseline measures (171 in the intervention group and 148 in the control group), and 291 dyads completed endline measures (160 in the intervention group and 131 in the control group). At endline, children in the intervention group had significantly higher cognitive scores (58·90 vs 55·65, effect size 0·36, 95% CI 0·12-0·59) and receptive language scores (23·86 vs 22·40, 0·27, 0·03-0·50) than did children in the control group. Mothers in the intervention group reported significantly fewer depressive symptoms (15·36 vs 18·61, -0·391, 95% CI -0·62 to -0·16) than did mothers in the control group. However, no differences were found in child growth between groups. Interpretation: The 12 session integrated parenting intervention delivered by non-professional community members improved child development and maternal wellbeing in rural Uganda. Because this intervention was largely managed and implemented by a local organisation, using local community members and minimal resources, such a programme has the potential to be replicated and scaled up in other low-resource, village-based settings. Funding: Plan Uganda via Plan Finland (Ministry of Foreign Affairs) and Plan Australia (Australian Aid).

The Lancet. Global health · randomised controlled trial · 208 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Computerized Cognitive Training for Amelioration of Cognitive Late Effects Among Childhood Cancer Survivors: A Randomized Controlled Trial.

Purpose: Children receiving CNS-directed therapy for cancer are at risk for cognitive problems, with few available empirically supported interventions. Cognitive problems indicate neurodevelopmental disruption that may be modifiable with intervention. This study evaluated short-term efficacy of a computerized cognitive training program and neural correlates of cognitive change. Patient and methods: A total of 68 survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) with identified cognitive deficits were randomly assigned to computerized cognitive intervention (male, n = 18; female, n = 16; ALL, n = 23; BT, n = 11; mean age ± standard deviation, 12.21 ± 2.47 years) or waitlist (male, n = 18; female, n = 16; ALL, n = 24; BT, n = 10; median age ± standard deviation, 11.82 ± 2.42 years). Intervention participants were asked to complete 25 training sessions at home with weekly, telephone-based coaching. Cognitive assessments and functional magnetic resonance imaging scans (intervention group) were completed pre- and postintervention, with immediate change in spatial span backward as the primary outcome. Results: Survivors completing the intervention (n = 30; 88%) demonstrated greater improvement than controls on measures of working memory (mean ± SEM; eg, Wechsler Intelligence Scale for Children [fourth edition; WISC-IV] spatial span backward, 3.13 ± 0.58 v 0.75 ± 0.43; P = .002; effect size [ES], 0.84), attention (eg, WISC-IV spatial span forward, 3.30 ± 0.71 v 1.25 ± 0.39; P = .01; ES, 0.65), and processing speed (eg, Conners' Continuous Performance Test hit reaction time, -2.10 ± 1.47 v 2.54 ± 1.25; P = .02; ES, .61) and showed greater reductions in reported executive dysfunction (eg, Conners' Parent Rating Scale III, -6.73 ± 1.51 v 0.41 ± 1.53; P = .002; ES, 0.84). Functional magnetic resonance imaging revealed significant pre- to post-training reduction in activation of left lateral prefrontal and bilateral medial frontal areas. Conclusion: Study findings show computerized cognitive training is feasible and efficacious for childhood cancer survivors, with evidence for training-related neuroplasticity.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 119 citationsread the source →

Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer: Outcomes From the ENABLE III Randomized Controlled Trial.

Purpose: To determine the effect of early versus delayed initiation of a palliative care intervention for family caregivers (CGs) of patients with advanced cancer. Patients and methods: Between October 2010 and March 2013, CGs of patients with advanced cancer were randomly assigned to receive three structured weekly telephone coaching sessions, monthly follow-up, and a bereavement call either early after enrollment or 3 months later. CGs of patients with advanced cancer were recruited from a National Cancer Institute cancer center, a Veterans Administration Medical Center, and two community outreach clinics. Outcomes were quality of life (QOL), depression, and burden (objective, stress, and demand). Results: A total of 122 CGs (early, n = 61; delayed, n = 61) of 207 patients participated; average age was 60 years, and most were female (78.7%) and white (92.6%). Between-group differences in depression scores from enrollment to 3 months (before delayed group started intervention) favored the early group (mean difference, -3.4; SE, 1.5; d = -.32; P = .02). There were no differences in QOL (mean difference, -2; SE, 2.3; d = -.13; P = .39) or burden (objective: mean difference, 0.3; SE, .7; d = .09; P = .64; stress: mean difference, -.5; SE, .5; d = -.2; P = .29; demand: mean difference, 0; SE, .7; d = -.01; P = .97). In decedents' CGs, a terminal decline analysis indicated between-group differences favoring the early group for depression (mean difference, -3.8; SE, 1.5; d = -.39; P = .02) and stress burden (mean difference, -1.1; SE, .4; d = -.44; P = .01) but not for QOL (mean difference, -4.9; SE, 2.6; d = -.3; P = .07), objective burden (mean difference, -.6; SE, .6; d = -.18; P = .27), or demand burden (mean difference, -.7; SE, .6; d = -.23; P = .22). Conclusion: Early-group CGs had lower depression scores at 3 months and lower depression and stress burden in the terminal decline analysis. Palliative care for CGs should be initiated as early as possible to maximize benefits.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 342 citationsread the source →

Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies.

Background: Approximately 15 million people who suffer a stroke globally each year are at risk of developing depression. Aim: To update our systematic review and meta-analysis of the frequency of depression after stroke published in 2005, including studies published before July 2004. Methods: We included all published observational studies (to 31 May 2013) with prospective consecutive recruitment and quantification of the proportion of people with depression after stroke. We included studies of adult (>18 years) patients with a clinical diagnosis of stroke, where an assessment of depression or depressive symptom burden was performed at a pre-specified time-point for all study participants. Results: Data were available from 61 studies including 25,488 people. The proportional frequency of depression varied considerably across studies; however, the pooled frequency estimate of 31% (95% confidence interval 28% to 35%) was not significantly different from the 33% (difference of 2%, 95% confidence interval <1% to 3%) reported in the 2005 review. The proportion with depression between one and five-years (25%; 95% confidence interval 16 to 33%) and at five years after stroke (23%; 95% confidence interval 14 to 31%) was significantly lower. Conclusion: Despite systematic review evidence describing validated depression screening tools and effective treatment and prevention strategies for depression after stroke, there has not been a significant reduction in the proportion of people experiencing depression after stroke. There is a pressing need for increased clinical uptake of evidenced-based strategies to screen for, prevent, and treat depression after stroke.

International journal of stroke : official journal of the International Stroke Society · meta-analysis · 738 citationsread the source →

The effectiveness of case-based learning in health professional education. A BEME systematic review: BEME Guide No. 23.

Background: Case-based learning (CBL) is a long established pedagogical method, which is defined in a number of ways depending on the discipline and type of 'case' employed. In health professional education, learning activities are commonly based on patient cases. Basic, social and clinical sciences are studied in relation to the case, are integrated with clinical presentations and conditions (including health and ill-health) and student learning is, therefore, associated with real-life situations. Although many claims are made for CBL as an effective learning and teaching method, very little evidence is quoted or generated to support these claims. We frame this review from the perspective of CBL as a type of inquiry-based learning. Aim: To explore, analyse and synthesise the evidence relating to the effectiveness of CBL as a means of achieving defined learning outcomes in health professional prequalification training programmes. Method: Selection criteria: We focused the review on CBL for prequalification health professional programmes including medicine, dentistry, veterinary science, nursing and midwifery, social care and the allied health professions (physiotherapy, occupational therapy, etc.). Papers were required to have outcome data on effectiveness. Search strategies: The search covered the period from 1965 to week 4 September 2010 and the following databases: ASSIA, CINAHL, EMBASE, Education Research, Medline and Web of Knowledge (WoK). Two members of the topic review group (TRG) independently reviewed the 173 abstracts retrieved from Medline and compared findings. As there was good agreement on inclusion, one went onto review the WoK and ASSIA EndNote databases and the other the Embase, CINAHL and Education Research databases to decide on papers to submit for coding. Coding and data analysis: The TRG modified the standard best evidence medical education coding sheet to fit our research questions and assessed each paper for quality. After a preliminary reliability exercise, each full paper was read and graded by one reviewer with the papers scoring 3-5 (of 5) for strength of findings being read by a second reviewer. A summary of each completed coding form was entered into an Excel spread sheet. The type of data in the papers was not amenable to traditional meta-analysis because of the variability in interventions, information given, student numbers (and lack of) and timings. We, therefore, adopted a narrative synthesis method to compare, contrast, synthesise and interpret the data, working within a framework of inquiry-based learning. Results: The final number of coded papers for inclusion was 104. The TRG agreed that 23 papers would be classified as of higher quality and significance (22%). There was a wide diversity in the type, timing, number and length of exposure to cases and how cases were defined. Medicine was the most commonly included profession. Numbers of students taking part in CBL varied from below 50 to over 1000. The shortest interventions were two hours, and one case, whereas the longest was CBL through a whole year. Group sizes ranged from students working alone to over 30, with the majority between 2 and 15 students per group. The majority of studies involved single cohorts of students (61%), with 29% comparing multiple groups, 8% involving different year groups and 2% with historical controls. The outcomes evaluation was either carried out postintervention only (78 papers; 75%), preintervention and postintervention (23 papers; 22%) or during and postintervention (3 papers; <3%). Our analysis provided the basis for discussion of definitions of CBL, methods used and advocated, topics and learning outcomes and whether CBL is effective based on the evaluation data. Conclusion: Overwhelmingly, students enjoy CBL and think that it enhances their learning. The empirical data taken as a whole are inconclusive as to the effects on learning compared with other types of activity. Teachers enjoy CBL, partly because it engages, and is perceived to motivate, students. CBL seems to foster learning in small groups though whether this is the case delivery or the group learning effect is unclear.

Medical teacher · systematic review · 534 citationsread the source →

Disclosure and health-seeking behaviour following intimate partner violence before and during pregnancy in Flanders, Belgium: a survey surveillance study.

Objectives: The objectives were to estimate the prevalence of physical and sexual intimate partner violence (IPV) among a regional sample of the general obstetric population as the lifetime prevalence, as the 1-year period prevalence before pregnancy, and as the prevalence during the index pregnancy; to assess the rates of disclosure and help-seeking behaviour with IPV; and to determine the acceptability of screening for IPV. Study design: A multi-centred survey surveillance study was carried out among pregnant women attending five large hospitals in the province of East Flanders, Belgium as a regional probability sample of the general obstetric population. Data were collected through an anonymous, written questionnaire that included the Abuse Assessment Screen and additional questions on the circumstances of the most recent episode of physical or sexual violence, on disclosure and help-seeking behaviour, on reporting assault to the police, and on the acceptability of routine screening for IPV. Results: The sampling frame consisted of 1362 women who received the questionnaire at the antenatal service during a 2-month study period, of which 537 (mean age 29.4 years, S.D. 4.09) returned the envelope (response rate 39.4%). The lifetime prevalence of IPV was estimated to be 10.1% (95% CI 7.7-13.0%) and the period prevalence of IPV during pregnancy and/or in the year preceding pregnancy 3.4% (95% CI 2.1-5.4%). There was a significant difference in the reported lifetime prevalence of IPV between women attending with a partner and those who came to the prenatal visit unattended by their partner in particular (6.8% versus 13.9%, p=0.010). Overall, only 19.2% (23 out of 120) and as few as 6.6% (4 out of 61) of the victims of physical and sexual abuse respectively sought medical care by consulting a general practitioner, gynaecologist, or an emergency department. Routine screening for IPV by a general practitioner or gynaecologist was found to be largely acceptable. Conclusions: In our highly medicalised society, women experiencing partner violence rarely disclose abuse to the widely available health care services, unless they are directly asked about it, which appears an acceptable practice. Hence, there is a definite need to improve women's awareness regarding abuse and their help-seeking behaviour at a public health level.

European journal of obstetrics, gynecology, and reproductive biology · cohort or longitudinal · 40 citationsread the source →

Improvements in advance care planning in the Veterans Affairs System: results of a multifaceted intervention.

Background: Advance care planning (ACP) aims to guide health care in the event of decisional incapacity. Interventions to promote ACP have had limited effectiveness. We conducted an educational and motivational intervention in Department of Veterans Affairs outpatient clinics to increase ACP use and proxy and health care provider understanding of patients' preferences and values. Methods: We recruited 23 providers and up to 14 of each of their patients; the patients were randomized to the control or intervention group. Eligibility criteria included a preexisting relationship with the provider, age 55 years or older, chronic health condition(s), and no recorded advance directive. The intervention group (n = 119) received an ACP workbook, motivational counseling by social workers, and cues to providers to discuss ACP. The control group (n = 129) received an advance directive booklet. Results: The intervention patients reported more ACP discussions with their providers (64% vs 38%; P<.001). Living wills were filed in the medical record twice as often in the intervention group (48% vs 23%; P<.001). Provider-patient dyads in the intervention group had higher agreement scores than the control group for treatment preferences, values, and personal beliefs (58% vs 48%, 57% vs 46%, and 61% vs 47%, respectively; P<.01 for all comparisons). The agreement scores for the proxy-patient dyads did not differ between groups for treatment preferences and values, but were higher in the intervention than the control group for personal beliefs (67% vs 56%). Conclusion: This intervention demonstrates mixed results and highlights the ongoing challenges of helping health care providers and potential proxy decision makers represent patient preferences and values.

Archives of internal medicine · randomised controlled trial · 89 citationsread the source →

Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: A randomized controlled trial.

Background: The purpose of this study was to compare an early behavioral intervention (EBI) with nonstructured standard physical care (routine care intervention [RCI]) in preventing antipsychotic-induced weight gain in drug-naive first-episode psychosis patients. Method: Sixty-one patients with a DSM-IV-diagnosed psychotic disorder were first randomly assigned to 3 different antipsychotic treatments (risperidone [N = 23], olanzapine [N = 18], and haloperidol [N = 21]) and subsequently randomly assigned to the intervention condition (EBI, N = 35) or RCI (N = 27). EBI was specifically designed to teach strategies to enhance control over factors associated with antipsychotic-induced weight gain and consisted of 8 flexible intervention modules that incorporated behavioral interventions, nutrition, and exercise. In the RCI group, patients were informed about potential weight gain and advised to increase their exercise and limit food intake. Body weight and body mass index were measured at baseline and then weekly for 3 months. In addition to change in weight and body mass index, a third outcome measure was the proportion of patients who had gained more than 7% of their body weight at 3 months. Participating patients were referred between August 2002 and September 2004. Results: All 61 participants completed the study. Patients in the EBI group gained significantly less weight (mean = 4.1 kg, SD = 4.0) than those allocated to the RCI group (mean = 6.9 kg, SD = 4.5) (p < .01) during the 3-month follow-up period. Similar findings were obtained when both groups were compared on treatment-induced change in body mass index, which was significantly less in the EBI group than in the RCI group (1.40 vs. 2.39 kg/m2) (p < .01). Accordingly, significantly fewer patients in the EBI group (N = 11; 39.3%) than in the RCI group (N = 26; 78.8%) (p < .002) increased their baseline weight by more than 7%, the cutoff for clinically meaningful weight gain. Conclusions: EBI was effective in attenuating antipsychotic-induced weight gain in a drug-naive first-episode psychosis cohort. Patients displayed good adherence to this type of preventive intervention.

The Journal of clinical psychiatry · randomised controlled trial · 121 citationsread the source →

Sumatriptan-naproxen for acute treatment of migraine: a randomized trial.

Context: Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex, and multimechanism-targeted therapy may confer advantages over monotherapy. Objective: To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine. Design, setting, and participants: Two replicate, randomized, double-blind, single-attack, parallel-group studies conducted among 1461 (study 1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack. Interventions: Patients were randomized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan, 85 mg, and naproxen sodium, 500 mg; sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or placebo, to be used after onset of a migraine with moderate to severe pain. Main outcome measures: Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing, absence of photophobia, absence of phonophobia, and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo, and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy. Results: Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing (study 1, 65% vs 28%; P<.001 and study 2, 57% vs 29%; P<.001), absence of photophobia at 2 hours (58% vs 26%; P<.001 and 50% vs 32%; P<.001), and absence of phonophobia at 2 hours (61% vs 38%; P<.001 and 56% vs 34%; P<.001). The absence of nausea 2 hours after dosing was higher with sumatriptan-naproxen sodium than placebo in study 1 (71% vs 65%; P = .007), but in study 2 rates of absence of nausea did not differ between sumatriptan-naproxen sodium and placebo (65% vs 64%; P = .71). For 2- to 24-hour sustained pain-free response, sumatriptan-naproxen sodium was superior at P<.01 (25% and 23% in studies 1 and 2, respectively) to sumatriptan monotherapy (16% and 14% in studies 1 and 2), naproxen sodium monotherapy (10% and 10% in studies 1 and 2), and placebo (8% and 7% in studies 1 and 2). The incidence of adverse events was similar between sumatriptan-naproxen sodium and sumatriptan monotherapy. Conclusion: Sumatriptan, 85 mg, plus naproxen sodium, 500 mg, as a single tablet for acute treatment of migraine resulted in more favorable clinical benefits compared with either monotherapy, with an acceptable and well-tolerated adverse effect profile. Trial registration: clinicaltrials.gov Identifiers: NCT00434083 (study 1); NCT00433732 (study 2).

JAMA · randomised controlled trial · 181 citationsread the source →

Patients' and Parents' Needs, Attitudes, and Perceptions About Early Palliative Care Integration in Pediatric Oncology.

Importance: Early palliative care integration for cancer patients is now touted as the optimal care model, yet significant barriers often prevent its implementation. A perceived barrier, especially for pediatric oncology patients, is the notion that patients and their families may not need or want palliative care involvement early in the disease trajectory. Objective: To determine the perception of symptom burden early in treatment and assess attitudes toward early integration of palliative care in pediatric oncology patient-parent pairs. Design, setting, and participants: Novel but pretested survey tools were administered to 129 patient-parent dyads of hospital-based pediatric oncology ambulatory clinics and inpatient units between September 2011 and January 2015. All patient participants were aged between 10 and 17 years and were diagnosed as having an oncologic condition 1 month to 1 year before enrollment. Both the patient and the parent in the dyad spoke English, and all participating parents provided written informed consent. A convenience sample was used for selection, with participants screened when otherwise presenting at a participating site. A total of 280 eligible participants were approached for study inclusion, 258 of whom were enrolled in the study (92.1% positive response-rate). Main outcomes and measures: Degree of perceived suffering from early symptom-related causes, attitudes toward early palliative care integration, and patient-parent concordance. Statistical analysis included descriptive statistics, calculation of concordance, McNemar test results, and Cochran-Armitage trend test results. Results: Of the 129 patients in the dyads, 68 were boys, and 61 girls; of the 129 parents, 15 were men, and 114 women. Patients reported the following symptoms in the first month of cancer therapy: nausea (n = 109; 84.5%), loss of appetite (n = 97; 75.2%), pain (n = 96; 74.4%), anxiety (n = 77; 59.7%), constipation (n = 69; 53.5%), depression (n = 64; 49.6%), and diarrhea (n = 52; 40.3%). A large proportion of those reporting suffering indicated substantial suffering severity from specific symptoms (ie, a great deal or a lot) including nausea, 52.3% (57 of 109), loss of appetite, 50.5% (49 of 97), constipation 30.4% (21 of 69), pain 30.2% (29 of 96), anxiety 28.6% (22 of 77), depression 28.1% (18 of 64), and diarrhea 23.1% (12 of 52). Few children and parents expressed opposition to early palliative care involvement (2 [1.6%] and 8 [6.2%]) or perceived any detrimental effects on their relationship with their oncologist (6 [4.7%] and 5 [3.9%]), loss of hope (3 [2.3%] and 10 [7.8%]), or therapy interference (3 [2.3%] and 2 [1.6%], respectively). Intradyad concordance was low overall: 26% to 29% for exact concordance and 40% to 69% for agreement within 1 response category. Significant differences in patient-parent attitudes toward aspects of early palliative care included child participants being more likely than their parents (40.3% [n = 52] vs 17.8% [n = 23]) to indicate that palliative care would have been helpful for treating their symptoms (P < .001). Conclusions and relevance: Pediatric oncology patients experience a high degree of symptom-related suffering early in cancer therapy, and very few patients or parents in this study expressed negative attitudes toward early palliative care. Our findings suggest that pediatric oncology patients and families might benefit from, and are not a barrier to, early palliative care integration in oncology.

JAMA oncology · cohort or longitudinal · 148 citationsread the source →

A cross-sectional analysis of Trichomonas vaginalis infection among heterosexual HIV-1 serodiscordant African couples.

Objectives: Trichomonas vaginalis is the most prevalent curable STI worldwide and has been associated with adverse health outcomes and increased HIV-1 transmission risk. We conducted a cross-sectional analysis among couples to assess how characteristics of both individuals in sexual partnerships are associated with the prevalence of male and female T. vaginalis infection. Methods: African HIV-1 serodiscordant heterosexual couples were concurrently tested for trichomoniasis at enrolment into two clinical trials. T. vaginalis testing was by nucleic acid amplification or culture methods. Using Poisson regression with robust standard errors, we identified characteristics associated with trichomoniasis. Results: Among 7531 couples tested for trichomoniasis, 981 (13%) couples contained at least one infected partner. The prevalence was 11% (n=857) among women and 4% (n=319) among men, and most infected individuals did not experience signs or symptoms of T. vaginalis. Exploring concordance of T. vaginalis status within sexual partnerships, we observed that 61% (195/319) of T. vaginalis-positive men and 23% (195/857) of T. vaginalis-positive women had a concurrently infected partner. In multivariable analysis, having a T. vaginalis-positive partner was the strongest predictor of infection for women (relative risk (RR) 4.70, 95% CI 4.10 to 5.38) and men (RR 10.09, 95% CI 7.92 to 12.85). For women, having outside sex partners, gonorrhoea, and intermediate or high Nugent scores for bacterial vaginosis were associated with increased risk of trichomoniasis, whereas age 45 years and above, being married, having children and injectable contraceptive use were associated with reduced trichomoniasis risk. Additionally, women whose male partners were circumcised, had more education or earned income had lower risk of trichomoniasis. Conclusions: We found that within African HIV-1 serodiscordant heterosexual couples, the prevalence of trichomoniasis was high among partners of T. vaginalis-infected individuals, suggesting that partner services could play an important role identifying additional cases and preventing reinfection. Our results also suggest that male circumcision may reduce the risk of male-to-female T. vaginalis transmission.

Sexually transmitted infections · 10 citationsread the source →

Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome.

Objective: The 22q11.2 deletion syndrome is the most common known genetic risk factor for the development of schizophrenia. The authors conducted a longitudinal evaluation of adolescents with 22q11.2 deletion syndrome to identify early risk factors for the development of psychotic disorders. Method: Sixty children, 31 with 22q11.2 deletion syndrome and 29 comparison subjects with idiopathic developmental disability matched for age and IQ, underwent a baseline evaluation between 1998 and 2000; of these, 51 children (28 and 23 in the two groups, respectively) underwent follow-up evaluation between 2003 and 2005. A standardized comprehensive psychiatric, psychological, and adaptive functioning evaluation was conducted in both waves. Participants with 22q11.2 deletion syndrome were also genotyped for the catechol O-methyltransferase (COMT) Met/Val polymorphism and underwent magnetic resonance imaging scans. Results: The two groups had similar baseline neuropsychiatric profiles. At follow-up, 32.1% of subjects with 22q11.2 deletion syndrome had developed psychotic disorders as compared with 4.3% of comparison subjects. In the 22q11.2 deletion syndrome group, baseline subthreshold psychotic symptoms interacted both with the COMT genotype and with baseline symptoms of anxiety or depression to predict 61% of the variance in severity of psychosis at follow-up evaluation. Lower baseline verbal IQ was also associated with more severe psychotic symptoms at follow-up evaluation. Conclusions: Genetic, cognitive, and psychiatric risk factors for the evolution of psychotic disorders in 22q11.2 deletion syndrome during adolescence were identified. Early intervention in the subgroup of children with subthreshold signs of psychosis and internalizing symptoms (especially anxiety symptoms) may reduce the risk of developing psychotic disorders during adolescence.

The American journal of psychiatry · cohort or longitudinal · 174 citationsread the source →

Telemedicine Applications for Cancer Rehabilitation: Scoping Review.

Background: Cancer is a significant public health issue worldwide. Treatments such as surgery, chemotherapy, and radiation therapy often cause psychological and physiological side effects, affecting patients' ability to function and their quality of life (QoL). Physical activity is crucial to cancer rehabilitation, improving physical function and QoL and reducing cancer-related fatigue. However, many patients face barriers to accessing cancer rehabilitation due to socioeconomic factors, transportation issues, and time constraints. Telerehabilitation can potentially overcome these barriers by delivering rehabilitation remotely. Objective: The aim of the study is to identify how telemedicine is used for the rehabilitation of patients with cancer. Methods: This scoping review followed recognized frameworks. We conducted an electronic literature search on PubMed for studies published between January 2015 and May 2023. Inclusion criteria were studies reporting physical therapy telerehabilitation interventions for patients with cancer, including randomized and nonrandomized controlled trials, feasibility studies, and usability studies. In total, 21 studies met the criteria and were included in the final review. Results: Our search yielded 37 papers, with 21 included in the final review. Randomized controlled trials comprised 47% (n=10) of the studies, with feasibility studies at 33% (n=7) and usability studies at 19% (n=4). Sample sizes were typically 50 or fewer participants in 57% (n=12) of the reports. Participants were generally aged 65 years or younger (n=17, 81%), with a balanced gender distribution. Organ-specific cancers were the focus of 66% (n=14) of the papers, while 28% (n=6) included patients who were in the posttreatment period. Web-based systems were the most used technology (n=13, 61%), followed by phone call or SMS text messaging-based systems (n=9, 42%) and mobile apps (n=5, 23%). Exercise programs were mainly home based (n=19, 90%) and included aerobic (n=19, 90%), resistance (n=13, 61%), and flexibility training (n=7, 33%). Outcomes included improvements in functional capacity, cognitive functioning, and QoL (n=10, 47%); reductions in pain and hospital length of stay; and enhancements in fatigue, physical and emotional well-being, and anxiety. Positive effects on feasibility (n=3, 14%), acceptability (n=8, 38%), and cost-effectiveness (n=2, 9%) were also noted. Functional outcomes were frequently assessed (n=19, 71%) with tools like the 6-minute walk test and grip strength tests. Conclusions: Telerehabilitation for patients with cancer is beneficial and feasible, with diverse approaches in study design, technologies, exercises, and outcomes. Future research should focus on developing standardized methodologies, incorporating objective measures, and exploring emerging technologies like virtual reality, wearable or noncontact sensors, and artificial intelligence to optimize telerehabilitation interventions. Addressing these areas can enhance clinical practice and improve outcomes for remote rehabilitation with patients.

JMIR cancer · review · 17 citationsread the source →

A review and content analysis of engagement, functionality, aesthetics, information quality, and change techniques in the most popular commercial apps for weight management.

Background: There are thousands of apps promoting dietary improvement, increased physical activity (PA) and weight management. Despite a growing number of reviews in this area, popular apps have not been comprehensively analysed in terms of features related to engagement, functionality, aesthetics, information quality, and content, including the types of change techniques employed. Methods: The databases containing information about all Health and Fitness apps on GP and iTunes (7,954 and 25,491 apps) were downloaded in April 2015. Database filters were applied to select the most popular apps available in both stores. Two researchers screened the descriptions selecting only weight management apps. Features, app quality and content were independently assessed using the Mobile App Rating Scale (MARS) and previously-defined categories of techniques relevant to behaviour change. Inter-coder reliabilities were calculated, and correlations between features explored. Results: Of the 23 popular apps included in the review 16 were free (70%), 15 (65%) addressed weight control, diet and PA combined; 19 (83%) allowed behavioural tracking. On 5-point MARS scales, apps were of average quality (Md = 3.2, IQR = 1.4); "functionality" (Md = 4.0, IQR = 1.1) was the highest and "information quality" (Md = 2.0, IQR = 1.1) was the lowest domain. On average, 10 techniques were identified per app (range: 1-17) and of the 34 categories applied, goal setting and self-monitoring techniques were most frequently identified. App quality was positively correlated with number of techniques included (rho = .58, p < .01) and number of "technical" features (rho = .48, p < .05), which was also associated with the number of techniques included (rho = .61, p < .01). Apps that provided tracking used significantly more techniques than those that did not. Apps with automated tracking scored significantly higher in engagement, aesthetics, and overall MARS scores. Those that used change techniques previously associated with effectiveness (i.e., goal setting, self-monitoring and feedback) also had better "information quality". Conclusions: Popular apps assessed have overall moderate quality and include behavioural tracking features and a range of change techniques associated with behaviour change. These apps may influence behaviour, although more attention to information quality and evidence-based content are warranted to improve their quality.

The international journal of behavioral nutrition and physical activity · review · 228 citationsread the source →

Inflammation and Schizophrenia

An association between inflammatory abnormalities and schizophrenia has been found repeatedly. The purposes of this special feature are to clarify the key findings on inflammation in schizophrenia, identify major gaps in the literature, and suggest priorities for research in this area. Inflammation is one of the body’s first lines of defense in response to injury or infection, and increased inflammation is found in many diseases. Acute inflammation is a nonspecific response characterized by warmth, pain, and swelling. Leukocytes migrate to the area of injury and become activated, the blood supply to the area increases, and blood vessels become more permeable, allowing cells and molecules to leave blood vessels and enter the injured tissue. The inflammatory response also involves the complement system, a group of proteins that, when activated, combine to form a complex molecular structure that kills cells, usually bacteria and parasites. Cytokines are key molecules that regulate inflammation; they also have important roles in the immune system. They are produced by a wide variety of immune cells and cells outside of the immune system. The term cytokine derives from their ability to influence the movement of inflammatory cells, but they also have other functions. Chronic inflammation is usually a lower grade response, lacks the grossly visible signs of acute inflammation, and may be systemic rather than localized. Chronic inflammation plays a role in the pathophysiology of many chronic diseases, including cardiovascular and cerebrovascular disease, diabetes, Alzheimer’s disease, and some cancers. The characteristics of chronic inflammation differ somewhat in the brain from what occurs in other tissues. An important component of neuroinflammation is the microglial activation. The brain contains relatively few of the inflammatory cells that are found outside the brain. Microglia, which are related to the peripheral inflammatory cells, serve some of the protective functions such cells play in the rest of the body. Microglia are involved in other brain functions, including the pruning and maintenance of synapses, trafficking of neurotransmitters, and devouring—phagocytosis—of cell fragments and damaged cells. Activated microglia produce inflammatory cytokines and the phagocytose cells or proteins that provoke the inflammatory response. Microglial activation and subsequent proinflammatory cytokine production may disrupt the blood-brain barrier (BBB). An intact BBB usually tightly controls the entry of cytokines and leukocytes into brain tissue. Damage to the BBB impairs its ability to control which inflammatory cells and molecules enter the brain; other substances leak into brain tissue, and the brain is unable to function normally. A discussion of prenatal inflammation as a risk factor for schizophrenia is beyond the scope of the present special feature, and the reader is referred to previous reviews of human1,2 and animal studies.3–6 Numerous studies have found that people with schizophrenia have increased blood concentrations of inflammatory cytokines.7 Two important themes emerge from these studies. First, inflammatory abnormalities are present in subjects with first-episode, drug-naive psychosis (FEP) compared with controls, suggesting an association that may be independent of the effects of antipsychotic medications. Second, the concentrations of some inflammatory molecules may vary with the clinical status of patients: ie, there appear to be separate groups of state and trait markers. The state-related markers include interleukin (IL) 1-beta, IL-6, and transforming growth factor-beta. People with schizophrenia have higher concentrations of these cytokines than controls during an exacerbation of symptoms, but there is no difference during periods of clinical stability. IL-12, interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) appear to be trait markers. Concentrations of these cytokines are higher in patients with FEP than in controls, and in patients with chronic illness, during both periods of symptomatic worsening, than in controls. C-reactive protein (CRP), another proinflammatory molecule, also appears to be a state marker,8 and specific lymphocyte populations may also segregate into state and trait markers.9 Additional evidence for potential state-related markers in schizophrenia has been reviewed elsewhere.10 Two studies suggest that inflammatory molecules may predict subsequent relapse.11,12 Other studies have found abnormal levels of inflammatory parameters in the central nervous system (CNS) in schizophrenia, including cerebrospinal fluid (CSF) cytokine11 and leukocyte levels,13,14 CNS microglia and lymphocytes,15–19 CSF and CNS oxidative stress,20,21 and anti-N-methyl-D-aspartate receptor autoantibodies.22 There is also evidence suggesting that infections may be associated with illness relapse.23 Within schizophrenia, blood cytokine abnormalities have been associated with poorer cognitive function and measures of regional brain volume24–26 and negative symptoms.27–30 There are several randomized clinical trials of the nonsteroidal anti-inflammatory drugs (NSAIDs) celecoxib and aspirin as adjuncts to antipsychotics.31 Interpretation of this evidence is complex, as these studies have not consistently distinguished relapsed from clinically stable patients. Furthermore, if inflammation plays a role in psychotic relapse, the efficacy of anti-inflammatory treatments may “disappear” in a lengthy trial because the treatment would not have any effect once patients have returned to their clinical baseline. However, an adjunctive agent that accelerates a patient’s antipsychotic response would be valuable. Agents other than NSAIDs that have anti-inflammatory properties, used in adjunct to antipsychotics, have been found to be superior to placebo. There have been two trials of minocycline,32,33 a second-generation tetracycline with anti-inflammatory and antimicrobial effects, that were superior to placebo. The efficacy of minocycline may have “disappeared” over the course of one trial,33 raising the possibility of an effect restricted to relapsed patient and not in those at a stable baseline. Adenosine is a purine nucleoside that modulates many physiological processes and has anti-inflammatory effects. A meta-analysis found that adjunctive treatment with adenosine-modulating drugs is superior to the effects of placebo.34 These drugs were associated with significant symptomatic improvement in inpatients, but not in outpatients, supporting the concept that state/trait differences may be an important predictor of antipsychotic response to adjunctive agents. Oxidative stress refers to an increase in free radicals, highly reactive molecules generated from metabolism and environmental exposures that can damage cell membranes. Inflammation and oxidative stress strongly influence each other.35 Antioxidant drugs decrease oxidative stress. One trial found that adjunctive treatment with the antioxidant N-acetylcysteine significantly reduced psychopathology in schizophrenia.36 A trial of fish oil, which also has significant anti-inflammatory effects, was conducted in adolescents and young adults with subthreshold psychotic symptoms,37 ie, “prodromal” patients. Patients receiving fish oil were significantly less likely to progress to a psychotic disorder than subjects receiving a placebo. Interestingly, fish oil was prescribed for 12 weeks, but the protective benefits with regards to transition to psychosis remained significant for 40 weeks after cessation of treatment. Inflammation may be a common mediator of diverse prenatal risk factors for schizophrenia, including preterm labor; preeclampsia (pregnancy-induced hypertension); neonatal birth asphyxia; and maternal gestational diabetes, stress, and depression.2 Maternal serum concentrations of the cytokines IL-838 and TNF-alpha39 during pregnancy were associated with an increased risk of schizophrenia in the offspring. Animal studies suggest that inflammation during critical periods of neurodevelopment may permanently alter the “set-point” of the inflammatory system, with increased inflammation in adult offspring.40–45 Meta-analyses have confirmed the presence of other abnormalities in schizophrenia that are associated with inflammation: increased autoantibodies,22 oxidative stress,46 CRP,8 and circulating lymphocytes.9 Antibodies are crucial “weapons” the immune system uses against foreign proteins. Autoantibodies, antibodies against a person’s own proteins, are associated with cytokine abnormalities.47 Lymphocytes, a group of white blood cells that combat infections, produce antibodies, and are an important source of cytokines, are increased in schizophrenia.9 Some subsets of lymphocytes may be state markers for acute psychosis, whereas others may be trait markers.9 CRP is a protein synthesized by the liver in response to inflammation, particularly IL-6 and other cytokines. Inflammation and oxidative stress may contribute to the decreased blood and CNS membrane levels of polyunsaturated fatty acids observed in schizophrenia.48 There are other disorders outside of schizophrenia in which peripheral inflammation appears to impact brain function. Inflammation is a risk factor for Alzheimer’s disease and mild cognitive impairment,49 rheumatoid arthritis is a risk factor for dementia,50 and “sickness behavior” is induced by peripheral cytokines.51,52 Depression is also associated with increased inflammation.53 The effects in depressed patients of an antibody against the cytokine TNF-alpha54 support the concept that brain function is impacted by peripheral cytokines. There are other mechanisms by which peripheral inflammation might cause or reflect brain dysfunction in schizophrenia. Cytokines may directly modulate dopaminergic neurotransmission55–57 or indirectly modulate glutamatergic neurotransmission through tryptophan metabolism.58–61 There is also some movement of peripheral leukocytes into the brain parenchyma, and the interaction of cytokines with the vagus nerve influences brain function.62 Blood cytokines induce cytokine production in the cells that form the BBB, and cytokines may move into the brain via the circumventricular organs, which lack a BBB.62 Inflammation may also disrupt the BBB, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. Some have suggested that the increase in blood concentrations of the protein S100-beta in schizophrenia63 is consistent with abnormal function of the BBB in people with schizophrenia, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. However, circulating S100-beta has sources other than the brain.64,65 Several potentially confounding variables are important to consider in studies of inflammation. Antipsychotics increase the risk of weight gain and diabetes, which are associated with inflammation. However, there is evidence from meta-analyses of abnormal inflammatory parameters in FEP,8,9,22,46 suggesting that the association between schizophrenia and inflammation is not solely due to antipsychotics. Antipsychotic-naïve relatives of people with schizophrenia also have increased inflammation compared with controls.66–68 Other potentially confounding variables include body mass index, age, gender, smoking, alcohol and illicit drug use, and whether patients are fasting at the time of sampling.69 The proportion of studies that either matched patients and controls, or statistically controlled for many of these potential confounders, has been low.8,9,22,46 Inflammation is comorbid with other physiological abnormalities, including hypertension, impaired glucose tolerance (fasting blood glucose [FBG] 100–126mg/dl), diabetes (FBG > 126, or a random blood glucose >200mg/dl), and increased oxidative stress. The associations with these other conditions also support the plausibility of increased inflammation in schizophrenia. However, the comorbidity of these physiological measures in schizophrenia complicates the interpretation of adjunctive treatment trials: what is the best therapeutic target? Another complicating issue is the relationship of inflammation to neurotropic viruses. One study found that treatment of patients with antibodies to herpes simplex 1 virus with a herpes-specific antiviral drug improved cognition with impressive effect sizes, suggesting the presence of an ongoing problem related to the virus.70 The association of other infectious agents with schizophrenia also raises the question of what relationship might exist between inflammation and either chronic infections or the expression of genes derived from an infectious agent and integrated into human DNA. The background presented above can be used to guide future research. Attempts to replicate current findings in well-matched patients and controls would be helpful. Cytokine levels in subjects with prodromal psychosis have not been investigated. We would hypothesize that these subjects should have abnormal trait markers compared with controls; within prodromal subjects, those who develop clinical psychosis should have abnormal state markers compared with high-risk subjects who do not. The effects of fish oil in preventing conversion to psychosis in high-risk subjects should be investigated in relationship to its effects on inflammation. The therapeutic anti-inflammatory agents that have been studied to date, such as aspirin, celecoxib, and fish oil, have multiple actions. Specific antibodies against individual cytokines are used in the treatment of rheumatoid arthritis and have been studied in depression.54 A change in symptoms or cognition in response to these antibodies would directly implicate inflammation in the pathophysiology of schizophrenia. More longitudinal studies with serial measurement of inflammatory parameters across the clinical course of illness are needed. It would be useful to test the hypothesis that patients with treatment-resistant schizophrenia have a different inflammatory profile than other patients with schizophrenia.7 Although it seems likely that there is increased inflammation in the brain when there are cytokine increases in the peripheral blood, the response might not be exactly the same in these two compartments. For instance, the inflammatory cytokines with altered levels in the brain might not be the same as those that change in the blood. More studies of markers of inflammation in the CNS—including CSF, postmortem analyses, and imaging studies—are needed. Two strategies may increase the signal-to-noise ratio for adjunctive trials of anti-inflammatory agents. First, inflammation may play a role in some patients with schizophrenia but not others. Patients with evidence of inflammation in the peripheral blood may be more likely to respond to an anti-inflammatory treatment strategy than those without inflammation and should be the ones included in treatment studies. Second, acutely ill and stable patients should be studied in separate trials and considered separately in meta-analyses. Furthermore, baseline-to-end-point analyses may not appropriate for studies of relapsed patients because there may be faster improvement with the use of adjunctive anti-inflammatories but not a greater total improvement by the end of the study. Studies of inflammation in schizophrenia should assess possible relationships of inflammatory cells and molecules to symptoms and cognition. To date, few studies have considered these measures.8,9,22,46 The comorbidity of inflammation, oxidative stress, hypertension, and abnormal glucose concentrations raise the issue what is the most appropriate treatment target in schizophrenia. As a first step in understanding this issue, it would be helpful to investigate relationships between inflammation, oxidative stress, hypertension, and glucose intolerance on the one hand, and clinical variables on the other. Several studies found that first-degree relatives of people with schizophrenia have increased inflammation and oxidative stress.66–68 It would advance the field to test the hypothesis that relatives have abnormal concentrations of the trait markers for schizophrenia but not of the state markers associated with relapse. Inflammatory molecules do not work in isolation but have complex interactions among themselves and with other systems. Most previous studies have measured only a small number of molecules. Concurrent measurement of cytokines, leukocytes, oxidative stress, and related parameters would increase the ability to make broader inferences regarding inflammation. Furthermore, if groups or clusters of covarying molecules—ie, molecules that change simultaneously—could be defined within schizophrenia, investigation of these groups is likely to yield better signal-to-noise ratios than individual molecules and should have more biological validity. Does increased inflammation due to infections or physical trauma increase the risk of relapse? If so, do preventive measures (eg, antibiotic prophylaxis for recurrent urinary tract infections)23 decrease that risk? What is the relationship between inflammation and the presence of antibodies to herpes viruses, toxoplasmosis, etc? Although the evidence on inflammation in schizophrenia is provocative, the number of studies in some areas is small, and increased methodological rigor is needed. Nonetheless, the evidence from FEP and first-degree relatives of patients with schizophrenia supports the idea that increased inflammation is truly associated with schizophrenia. This research raises the possibility that further study of inflammation will lead to greater understanding of the etiology and pathophysiology of schizophrenia. Dr B.K. is a member of Advisory Boards for Genentech and Roche. In the past 3 years, Dr B.J.M has received grant support from the National Institute of Mental Health (K23MH098014), the Georgia Regents University (GRU) Intramural Scientist Training Program, the GRU Brain & Behavior and Immunotherapy Discovery Institutes, the University of Oulu (Finland), the Thule Institute of the University of Oulu, and Oy H. Lundbeck Ab; research support from the National Institutes of Health Clinical Loan Repayment Program; consultancy fees for surveys from Medefied Europe and Plaza Research, on behalf of Genetech/Roche; speaker fees for grand rounds lectures from the Maryland Psychiatric Research Center and the Texas A&M University and Scott and White Hospital Department of Psychiatry; and payment for a survey from e-Rewards Medical Market Research.

Schizophrenia Bulletin · review · 315 citationsread the source →

The pleasure of art as a matter of fact

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Nadal Marcos and Skov Martin 2018The pleasure of art as a matter of factProc. R. Soc. B.2852017225220172252http://doi.org/10.1098/rspb.2017.2252SectionYou have accessCommentThe pleasure of art as a matter of fact Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed Search for more papers by this author and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Search for more papers by this author Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Published:21 March 2018https://doi.org/10.1098/rspb.2017.2252All other forms of perception divide a man, because they are exclusively based either on the sensuous or on the intellectual part of his being; only the perception of the Beautiful makes something whole of him, because both his natures must accord with it.— Schiller, 1793–1795, Letters on the Aesthetic Education of Man, p. 138, Letter 27Can art make us better people? Better members of society? In her recent article, 'Pleasure junkies all around! Why it matters and why "the arts" might be the answer: a biopsychological perspective', Christensen [1] claims that engaging with art can promote healthy choices, choices that balance short-term pleasure goals with long-term general well-being. She suggests that many modern life conveniences, such as social media, computer games or online shopping, have the potential to turn us into 'pleasure junkies' because they maximize short-term pleasures. But art, Christensen argues, is a safe choice and a means to remedy this unhealthy addiction to pleasure. Christensen's argument is grounded on three claims about the sort of pleasure we get from art. First, in contrast to low-level pleasure, which Christensen conceives as 'a mere perceptual stimulation leading to a rewarding sensation (food, sex, etc.)' ([1], p. 2), pleasure from art is presented as a kind of higher-order pleasure that engages 'broader neural networks implied in the attribution of meaning' (p. 2), presumably leading to 'long-term maintenance of healthy bodily function' (p. 2). Second, 'the arts do not induce states of craving without fulfilment—as do activities with reinforcement schedules which are prone to create habits and addictions such as intermittent variable ratio or interval reinforcement schedules (e.g. social media, gambling, football, extreme sports, drugs' (p. 4). Third, 'the arts do not search for a perceptual "Bliss point" […]. They do not just repeat over and over again a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch" (e.g. sugar, sexualized body displays, certain musical lyrics, tones; i.e. a perceptual "bliss point")' (p. 4).The claim, in a nutshell, is that the pleasure induced by art is different to the pleasure induced by food, sex, sports or drugs, because it is related to the balanced activation of brain systems related to short-term pleasure and long-term wellbeing goals, because it does not induce craving, and because it is not aimed at a perceptual 'bliss point'. This distinct sort of pleasure, according to Christensen, makes it possible for the arts to thwart the pernicious effects that the unhealthy urges and cravings licensed by 'today's mainstream acceptance of pleasure-seeking behaviour' (p. 5) have on individuals' lives and on societies. Such sweeping statements about art, food, sex, sports and society as a whole merit close examination. Christensen's primary claim that the pleasure induced by art is of a special kind, different to the pleasure induced by other activities is not supported by current understanding of what pleasure is. It is, moreover, contradicted by abundant empirical evidence. This evidence shows that pleasures, whatever their source, owe to activity in the same mesocorticolimbic circuit [2] and are encoded as a common neural currency [3]. As Kent Berridge and Morten Kringelbach put it: 'the brain mechanisms involved in fundamental pleasures (food and sexual pleasures) overlap with those for higher-order pleasures (e.g. monetary, artistic, musical, altruistic and transcendent pleasures) […] From sensory pleasures and drugs of abuse […] to monetary, aesthetic and musical delights, all pleasures seem to involve the same hedonic brain systems' ([4], p. 481). Thus, there is no evidence for specific brain regions or neural circuits related to the pleasure from art. Rather, the appreciation of art relies on brain mechanisms that evolved to appraise the value of biologically relevant objects in relation to internal homeostatic states [5]: 'Emotional reactions to music, further, activate the same cortical, subcortical and autonomic circuits, which are considered as the essential survival circuits of biological organisms in general' ([6], p. 6). In sum, the evidence shows that pleasure elicited by music and other art forms is no different in genesis and function to the pleasure induced by food, drugs and sex [7,8]. This is a matter of fact, not opinion. What supports Christensen's argument if not empirical evidence? In our view, her argument for the distinctness of art-induced pleasure seems based upon an oversimplified and devaluing conception of the pleasures of sex, food and sports, and a very narrow notion of art and its function. Christensen presents food, sex and sports as meaningless low-level sources of pleasure, and the arts as privileged vehicles for meaningful experiences. It is the personal and meaningful engagement with art—Christensen suggests—that fosters a balanced activation of brain systems related to short-term pleasure and long-term well-being goals. However, rarely—if ever—are food, sex and sports meaningless rewarding sensations. Contrary to Christensen's definition on page 2 of her article, pleasure—even sensory pleasure—is not simply reward, and never simply a sensation [4]. Indulging in food, sex or sports are meaningful and personally significant experiences that are not a matter of mere physical sensation. The experience of pleasure from food and sex is shaped by context, knowledge, expectations, anticipations, attitudes and beliefs that bring meaning to them [9–11]. Sex can be meaningful because it signifies physical connection with one's loved one, because it is cheating on someone, or deemed a sin. Likewise, eating is not about obtaining low-level pleasure. What we eat, the way we eat, what we believe about what we eat, where and whom we eat with, imbue eating with individual and social meaning, and shape the actual pleasure of eating [12]. On the other hand, encounters with art are not necessarily meaningful [13,14]. Actually, there is nothing intrinsically meaningful about engaging with art. Many laypeople lack the knowledge schemata required to engage meaningfully with abstract, cubist or contemporary art [15,16]. There are plenty of artworks people do not find meaningful or pleasant. Meaning making is not a special feature of art; it is a general feature of our species's cognition [17,18]. We can endow virtually any aspect of reality with meaning: sex, food, sports, a urinal, the shape of a cloud, an averted glance, someone's absence. Christensen's argument also rests on a historically and culturally narrow conception of art and its function. Art is presented as a circumscribed category of activities that elicit a unique sort of pleasant experiences: — The arts are set of activities of a special kind that share certain defining features distinguishing them from other activities: 'the arts push boundaries, surprise, reveal and excite both artist and spectator' ([1], p. 4).— Art encounters are positive, leading to 'pleasurable chills' and pleasurable experiences of understanding: 'The moment of meaning-assignation, also called "mastering" or "understanding" an artwork, is therefore a pleasurable experience' ([1], p. 4).— The pleasure elicited by art is special, because it does not involve craving for intense peaks: 'The arts do not search for a perceptual "bliss point" […] They do not just repeat over and over a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch"' ([1], p. 4).This characterization of the arts substantially overlaps with the notion of 'fine arts'. The core features of this characterization were instituted in the eighteenth century, after European intellectuals grouped certain activities into a distinct and autonomous collection, labelled 'fine arts'. To make sense of and promote this grouping, it became imperative to identify a common essence setting art apart from other activities [19,20,21]. One of the most popular proposals was that only art could produce a special sort of pleasure, sophisticated and polite [19,21]—a conception stemming not from any understanding of physiology, but from mere speculation. This limited historical and cultural scope renders this conception of the arts unfit for behavioural or neuroscientific research [19]. The category 'the arts' should not be mistaken for a natural kind. It is a historical convention, and has no direct biological correspondence. Moreover, this conception of art that Christensen espouses does not apply to art as practised in non-Western societies [19,22]. It does not even apply to Western art before the eighteenth century or after the nineteenth century [19,20,21]. First, art does not necessarily evoke pleasurable experiences. There are abundant artworks intended to arouse negative emotions [19,23], and to portray physical and moral ugliness [24]. Understanding art is not necessarily a pleasant experience: it can be an angering, disgusting or upsetting one [25]. Second, many artworks actually exploit repetition, bliss points and craving [26]. Repetition is a fundamental design feature of music and other performance arts [27]: In Relation in Space (1976) Marina Abramovic and Ulay ran into each other repeatedly for an hour; Ravel's Bolero is a 17 min-long instance of melodic and rhythmic repetitiveness. Anticipation and craving for bliss points are also essential to music [28]. In fact, the enjoyment of music is linked to intense feelings of anticipation and expectation caused by dopamine activity in the caudate nucleus (also involved in the rewarding aspect of food) [29,30], and peak pleasure states (bliss points) [31], caused by the release of dopamine and opioids in the brain's reward system (also involved in cocaine induced euphoria) [29,30]. Given the available evidence, therefore, there is no reason to believe that the pleasure from art is special or unique [32].In sum, Christensen's claim for the distinctiveness of pleasure from art is contradicted by empirical evidence, and her argument for the beneficial effects of art rests upon disputed foundations. Art's capacity to promote healthier choices and make us better people that can contribute to a better society remains as unconfirmed today as it was when Schiller speculated on art's power to harmonize human's conflicting sensuous and formal impulses. Christensen's argument is problematic even if intended to highlight hypothetical possibilities. Arguments about hypothetical possibilities should still rely on valid premises, and scientific hypotheses should be grounded on evidence, or at least in line with it. Otherwise, they are merely unfounded speculations. Scientific aesthetics is only just finding its footing and its place within cognitive neuroscience [33,34]. If evidence is ignored or rejected because it does not fit preconceived notions about art and its function, scientific aesthetics will become only an arena to promote and legitimize personally appealing notions of art by applying a scientific gloss over them. A proper scientific study of art needs to be grounded on empirical evidence and strong arguments that follow from solid premises [35,36]. Only then can scientific aesthetics provide reliable explanations for artistic and aesthetic behaviour, and thus make a significant contribution to the understanding of our human nature. Data accessibilityThis article has no additional data. Authors' contributionsBoth authors have contributed to conceiving, developing and writing the research presented in this paper, and approved it for publication. Competing interestsWe declare we have no competing interests. FundingThis research was supported by grant PSI2016-77327-P (MINECO/AEI/ERDF, EU).Footnotes© 2018 The Author(s)Published by the Royal Society. All rights reserved. References1Christensen JF. 2017Pleasure junkies all around! Why it matters and why 'the arts' might be the answer: a biopsychological perspective. Proc. R. Soc. B 284, 20162837. (doi:10.1098/rspb.2016.2837) Link, ISI, Google Scholar2Berridge CW, Kringelbach ML. 2013Neuroscience of affect: brain mechanisms of pleasure and displeasure. Curr. Opin. 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(doi:10.1016/j.plrev.2017.06.013) PubMed, ISI, Google Scholar Previous ArticleNext Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsCited by Clemente A, Pearce M, Skov M and Nadal M (2021) Evaluative judgment across domains: Liking balance, contour, symmetry and complexity in melodies and visual designs, Brain and Cognition, 10.1016/j.bandc.2021.105729, 151, (105729), Online publication date: 1-Jul-2021. Chuan-Peng H, Huang Y, Eickhoff S, Peng K and Sui J (2020) Seeking the "Beauty Center" in the Brain: A Meta-Analysis of fMRI Studies of Beautiful Human Faces and Visual Art, Cognitive, Affective, & Behavioral Neuroscience, 10.3758/s13415-020-00827-z, 20:6, (1200-1215), Online publication date: 1-Dec-2020. Skov M and Nadal M (2020) A Farewell to Art: Aesthetics as a Topic in Psychology and Neuroscience, Perspectives on Psychological Science, 10.1177/1745691619897963, 15:3, (630-642), Online publication date: 1-May-2020. Kalpokas I (2019) Making the Theory Political A Political Theory of Post-Truth, 10.1007/978-3-319-97713-3_4, (87-121), . Kalpokas I (2019) Affective Encounters of the Algorithmic Kind: Post-Truth and Posthuman Pleasure, Social Media + Society, 10.1177/2056305119845678, 5:2, (205630511984567), Online publication date: 1-Apr-2019. Skov M (2019) Aesthetic Appreciation: The View From Neuroimaging, Empirical Studies of the Arts, 10.1177/0276237419839257, 37:2, Online publication date: H, I and (2020) A for We Aesthetic in Human Neuroscience, A and in A New for Arts, This March Article in 2018 The Author(s)Published by the Royal Society. All rights Citations and are available with

Proceedings of the Royal Society B Biological Sciences · editorial or comment · 24 citationsread the source →

Better Together: Long-term Behaviors and Perspectives after a Practitioner-Family Writing Intervention in Clinical Practice.

Background: An expressive writing intervention, the Three-minute Mental Makeover (3MMM), was previously associated with reduced stress for practitioners, patients, and families. The goal of this follow-up study was to evaluate long-term use of writing and perspectives after participation in the 3MMM. Methods: The original study involved patients and families in the neonatal and pediatric Intensive Care Units, inpatient units, and outpatient clinics of a children's hospital. Health-care practitioners led the intervention, writing concurrently with patients and families using the 3MMM intervention. Follow-up contact by phone was attempted for all original patient/family participants 12 to 18 months after completing the exercise. Practitioners were contacted via email 24 months after the original study. Participants were surveyed about the 3MMM and continued use of writing to cope with stressful situations. Original and follow-up survey responses were compared using the Mann-Whitney test. Results: Of the 96 original patient/family members, 61 individuals were reached, remembered the 3MMM, and agreed to participate in the follow-up study. Among the 61 participants, 52 (85%) agreed that the 3MMM had been helpful. Thirty-six (59%) reported using writing to help cope with stress at follow-up, compared to only 23 (38%) at baseline (P = 0.005). The majority of clinicians (87%) also continued to use the 3MMM in clinical practice following the original 3MMM study period and ranked it as both feasible (75%) and worth the time investment (75%). Conclusion: The 3MMM demonstrated long-term perceived benefits and behavior changes. Findings provide preliminary support for using the 3MMM in routine clinical practice.

The Permanente journal · 2 citationsread the source →

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001-14: a case only analysis.

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18-89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001-14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001-14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53-1·70; fully adjusted OR 1·45, 95% CI 1·38-1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22-1·30; fully adjusted OR 1·18, 1·14-1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2-49·5) and lowest for women who were white with university education (29·4%, 28·2-30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%-17·2% in 1970-74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50-69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa.

The Lancet. Global health · 56 citationsread the source →

Impact of cognitive impairment on activities of daily living among older adults of North India.

Background: Older persons are at risk of developing cognitive impairment, often considered a precursor to more severe conditions, such as dementia or Alzheimer's disease. Cognitive impairment among older adults is one of the most rapidly growing burdens, especially in developing countries. Aim: To assess the impact of cognitive impairment on activities of daily living (ADL) among older adults. Materials and methods: A cross-sectional descriptive study was conducted among 135 older adults visiting a selected tertiary care centre in Uttarakhand (India) during December 2020, recruited using total enumerative sampling. Data were collected using standardized and validated tools that consisted of socio-demographic information, Hindi Mental Status Examination, and Everyday Abilities Scale for India. Data were analyzed using SPSS version 23, including descriptive (frequency, percentage, mean, and median) and inferential statistics (Chi-square test, binary logistic regression). Results: The results with pooled analysis have shown that 30% of the older adults had mild cognitive impairment, 9% had moderate cognitive impairment, and 61% had normal cognition. About 16% of the older adults' ADL were affected. The statistically significant predictors for cognitive impairment were age group 80 years [odds ratio (OR) = 36.21; 95% confidence interval (CI) = 6.23-210.59], Muslim religion (OR = 6.26; 95% CI = 1.12-34.93), and middle-class families (OR = 11.95; 95% CI = 1.84-77.78). Conclusion: A considerably large proportion of the older adults had cognitive impairment, which further impacted activities of daily living. There is an urgent need to develop geriatric mental health services across all hospitals in the region.

Journal of family medicine and primary care · 10 citationsread the source →

Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.

Background: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014. Methods: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years). Findings: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference -3·51 years, 95% CI -3·77 to -3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age. Interpretation: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled. Funding: British Heart Foundation and National Institute for Health Research.

Lancet (London, England) · 925 citationsread the source →

Association of Race and Ethnicity With Late-Life Depression Severity, Symptom Burden, and Care.

Importance: Knowledge gaps persist regarding racial and ethnic variation in late-life depression, including differences in specific depressive symptoms and disparities in care. Objective: To examine racial/ethnic differences in depression severity, symptom burden, and care. Design, setting, and participants: This cross-sectional study included 25 503 of 25 871 community-dwelling older adults who participated in the Vitamin D and Omega-3 Trial (VITAL), a randomized trial of cancer and cardiovascular disease prevention conducted from November 2011 to December 2017. Data analysis was conducted from June to September 2018. Exposure: Racial/ethnic group (ie, non-Hispanic white; black; Hispanic; Asian; and other, multiple, or unspecified race). Main outcomes and measures: Depressive symptoms, assessed using the Patient Health Questionnaire-8 (PHQ-8); participant-reported diagnosis, medication, and/or counseling for depression. Differences across racial/ethnic groups were evaluated using multivariable zero-inflated negative binomial regression to compare PHQ-8 scores and multivariable logistic regression to estimate odds of item-level symptom burden and odds of depression treatment among those with diagnosed depression. Results: There were 25 503 VITAL participants with adequate depression data (mean [SD] age, 67.1 [7.1] years) including 12 888 [50.5%] women, 17 828 [69.9%] non-Hispanic white participants, 5004 [19.6%] black participants, 1001 [3.9%] Hispanic participants, 377 [1.5%] Asian participants, and 1293 participants [5.1%] who were categorized in the other, multiple, or unspecified race group. After adjustment for sociodemographic, lifestyle, and health confounders, black participants had a 10% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (rate ratio [RR], 1.10; 95% CI, 1.04-1.17; P < .001); Hispanic participants had a 23% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (RR, 1.23; 95% CI, 1.10-1.38; P < .001); and participants in the other, multiple, or unspecified group had a 14% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (RR, 1.14; 95% CI, 1.04-1.25; P = .007). Compared with non-Hispanic white participants, participants belonging to minority groups had 1.5-fold to 2-fold significantly higher fully adjusted odds of anhedonia (among black participants: odds ratio [OR], 1.76; 95% CI, 1.47-2.11; among Hispanic participants: OR, 1.96; 95% CI, 1.43-2.69), sadness (among black participants: OR, 1.31; 95% CI, 1.07-1.60; among Hispanic participants: OR, 2.09; 95% CI, 1.51-2.88), and psychomotor symptoms (among black participants: OR, 1.77; 95% CI, 1.31-2.39; among Hispanic participants: OR, 2.12; 95% CI, 1.28-3.50); multivariable-adjusted odds of sleep problems and guilt appeared higher among Hispanic vs non-Hispanic white participants (sleep: OR, 1.24; 95% CI, 1.01-1.52; guilt: 1.84; 95% CI, 1.31-2.59). Among those with clinically significant depressive symptoms (ie, PHQ-8 score ≥10) and/or those with diagnosed depression, black participants were 61% less likely to report any treatment (ie, medications and/or counseling) than non-Hispanic white participants after adjusting for confounders (adjusted OR, 0.39; 95% CI, 0.27-0.56). Conclusions and relevance: In this cross-sectional study, significant racial and ethnic differences in late-life depression severity, item-level symptom burden, and depression care were observed after adjustment for numerous confounders. These findings suggest a need for further examination of novel patient-level and clinician-level factors underlying these associations.

JAMA network open · 78 citationsread the source →

Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding: Gates Foundation and Bloomberg Philanthropies.

Lancet (London, England) · 257 citationsread the source →

A Validation of Six Wearable Devices for Estimating Sleep, Heart Rate and Heart Rate Variability in Healthy Adults.

The primary aim of this study was to examine the validity of six commonly used wearable devices, i.e., Apple Watch S6, Garmin Forerunner 245 Music, Polar Vantage V, Oura Ring Generation 2, WHOOP 3.0 and Somfit, for assessing sleep. The secondary aim was to examine the validity of the six devices for assessing heart rate and heart rate variability during, or just prior to, night-time sleep. Fifty-three adults (26 F, 27 M, aged 25.4 ± 5.9 years) spent a single night in a sleep laboratory with 9 h in bed (23:00-08:00 h). Participants were fitted with all six wearable devices-and with polysomnography and electrocardiography for gold-standard assessment of sleep and heart rate, respectively. Compared with polysomnography, agreement (and Cohen's kappa) for two-state categorisation of sleep periods (as sleep or wake) was 88% (κ = 0.30) for Apple Watch; 89% (κ = 0.35) for Garmin; 87% (κ = 0.44) for Polar; 89% (κ = 0.51) for Oura; 86% (κ = 0.44) for WHOOP and 87% (κ = 0.48) for Somfit. Compared with polysomnography, agreement (and Cohen's kappa) for multi-state categorisation of sleep periods (as a specific sleep stage or wake) was 53% (κ = 0.20) for Apple Watch; 50% (κ = 0.25) for Garmin; 51% (κ = 0.28) for Polar; 61% (κ = 0.43) for Oura; 60% (κ = 0.44) for WHOOP and 65% (κ = 0.52) for Somfit. Analyses regarding the two-state categorisation of sleep indicate that all six devices are valid for the field-based assessment of the timing and duration of sleep. However, analyses regarding the multi-state categorisation of sleep indicate that all six devices require improvement for the assessment of specific sleep stages. As the use of wearable devices that are valid for the assessment of sleep increases in the general community, so too does the potential to answer research questions that were previously impractical or impossible to address-in some way, we could consider that the whole world is becoming a sleep laboratory.

Sensors (Basel, Switzerland) · 188 citationsread the source →

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.

World Psychiatry · editorial or comment · 607 citationsread the source →

Bullying and Suicide: A Public Health Approach

Several recent studies have found an association between bullying and depression [[1]Wang J. Iannotti R.J. Luk J.W. Nansel T.R. Co-occurrence of victimization from five subtypes of bullying: Physical, verbal, social exclusion, spreading rumors, and cyber.J Pediatr Psychol. 2010; 35: 1103-1112Crossref PubMed Scopus (223) Google Scholar] or bullying and suicide-related behaviors [[2]Kim Y.S. Leventhal B. Suicide and bullying. A review. Int J Adolesc Med Health. 2008; 20: 133-154Crossref PubMed Scopus (324) Google Scholar], and one study found evidence consistent with a causal link, at least for girls [3Klomek A.B. Sourander A. Niemela S. et al. Childhood bullying behaviors as a risk for suicide attempts and completed suicides: A population-based birth cohort study.J Am Acad Child Adolesc Psychiatry. 2009; 48: 254-261Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar, 4Klomek A.B. Sourander A. Gould A. The association of suicide and bullying in childhood to young adulthood: A review of cross-sectional and longitudinal research findings. Can J Psychiatry. 2010; 55: 282-288PubMed Google Scholar]. These studies, in conjunction with extensive media coverage of the deaths by suicide of several young people who were victims of bullying, led the Centers for Disease Control and Prevention (CDC) to convene an expert panel focusing on the relationship between bullying involvement and suicide-related behaviors. The purpose of the panel, held in September 2010, was to synthesize the latest research about the relationship between youth involvement in bullying (youth who bully, youth who are bullied, and those who bully and are bullied) and suicide-related behaviors (attempts, fatalities, and risk factors associated with suicide, such as depression). Experts on the topics of bullying and suicide presented their research about the relationship between these two behaviors; their work is contained in this supplement. The panel and this special issue provide clarity around the complicated issues of bullying and suicide among youth. Three key themes emerged: (1) bullying among youth is a significant public health problem; it is prevalent and frequently has detrimental effects; (2) there is a strong association between bullying and suicide-related behaviors, but this relationship is often mediated by other factors, including depression and delinquency; and (3) there are public health strategies that can be applied to the prevention of bullying and suicide. Bullying is a significant public health problem because it is prevalent and harmful. Between 20% and 56% of young people are involved in bullying annually [5Centers for Disease Control and Prevention. Youth risk behavior surveillance—United States, 2011. MMWR, Surveillance Summaries 2012;61(no. SS-4). Available at: www.cdc.gov/mmwr/pdf/ss/ss6104.pdf. Google Scholar, 6Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 7Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Thus, in a classroom of 30 students, between 6 and 17 students are involved in bullying as a victim, perpetrator, or both (bully-victim). The specific rate of bullying victimization and perpetration varies according to age, type of bullying, time period over which bullying behaviors are assessed, and by subgroup. Younger (middle school-aged) children are more likely to be involved in bullying than high school-aged children [[8]Robers S. Zhang J. Truman J. Indicators of school crime and safety: 2011 (NCES 2012-002/NCJ 236021). National Center for Education Statistics, U.S. Department of Education, and Bureau of Justice Statistics, Office of Justice Programs, U.S. Department of Justice, Washington, DC2012Google Scholar]. Verbal bullying is generally more prevalent than physical or cyber-bullying and bullying is more likely to occur over a longer time period—“ever” or over the “past year” as opposed to “the past few months” [[9]David-Ferdon C. Hertz M.F. Electronic media and youth violence: A CDC issue brief for researchers. Centers for Disease Control, Atlanta, GA2009Google Scholar]. Specific subgroups are more likely to be victimized. For example, bullying victimization is more prevalent upon lesbian and gay youth—60% report victimization during the past 30 days prior to the survey compared with 28.8% of heterosexual youth [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. For young people involved in bullying in any capacity—youth who bully others, who are bullied, or who both bully and are bullied, this involvement is correlated with poor mental and physical health and engagement in other risk behaviors. Youth who are bullied are more likely to be depressed or anxious [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar], have lower academic achievement, report feeling like they do not belong at school [[12]Glew G.M. Fan M. Katon W. et al. Bullying, psychosocial adjustment, and academic performance in elementary school. Arch Pediatr Adolesc Med. 2005; 159: 1026-1031Crossref PubMed Scopus (384) Google Scholar], have poorer social and emotional adjustment, greater difficulty making friends, poorer relationships with classmates, and greater loneliness [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Bully-victims are more likely than those who bully, those who are bullied, or their uninvolved peers to report being physically hurt by a family member, to witness family violence, and exhibit suicide-related behaviors [[14]McKenna M. Hawk E. Mullen J. Hertz M. The association between bullying behavior and health risks among middle school and high school students in Massachusetts, 2009.Morbidity and Mortality Weekly Review. 2011; 60: 465-471PubMed Google Scholar]. Those who bully others are more likely to drink alcohol and use cigarettes, to have poorer academic achievement and poorer perceived school climate, but to also report greater ease of making friends [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Involvement in bullying can also have long-lasting, detrimental effects months or even years after the bullying occurs. Young people who are bullied are more likely than uninvolved youth to develop depression and anxiety and report abdominal pain and feeling tense over the course of a school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. One study examining the impact of bullying victimization of those who were between 9, 11, and 13 years of age when they were victimized found, that over a 7-year period, youth who were bullied were more likely to develop generalized anxiety and panic disorder as adults while bully-victims were more likely to subsequently suffer from depression, panic disorder, and suicidality [[15]Copeland W.E. Wolke D. Angold A. Costello E.J. Adult psychiatric outcomes of bullying and being bullied by peers in childhood and adolescence.JAMA Psychiatry. 2013; 70: 419-426Crossref PubMed Scopus (746) Google Scholar]. Another longitudinal study found that those who were perpetrators of bullying at age 14 were more likely to receive a diagnosis of antisocial personality disorder, to have low job status at age 18 years, and to use drugs at ages 27–32 years [[16]Farrington D.P. Ttofi M.M. Bullying as a predictor of offending, violence and later life outcomes. Crim Behav Ment Health. 2011; 21: 90-98Crossref PubMed Scopus (169) Google Scholar]. The articles in this special issue generally show a strong association between involvement in bullying behaviors and suicide-related behaviors. In Espelage and Holt's work with middle school students, suicidal ideation and attempts were significantly more prevalent among victims, bully-victims and perpetrators, with rates of ideation and attempts among those involved as a victim, perpetrator, or bully-victims three to five times higher than the rate of uninvolved youth [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar]. Likewise, in Borowsky's study of 6th, 9th, and 12th graders, 1.2% of uninvolved youth made a suicide attempt, compared with 5% for those who frequently bullied others verbally or socially; 6.5% for those who were frequent victims of verbal/social bullying; and 11.1% for those who were frequent bully-victims of verbal/social bullying [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. In Kowalski and Limber's paper, depression, anxiety, self-esteem, self-reported health problems, absences from school, leaving school because of illness, and grades were, with only one exception, significantly related to students' involvement in cyber-bullying others, being cyber-bullied, bullying others through traditional means, and being bullied through traditional means [[7]Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Those who witness bullying but are not directly involved are also at increased risk. Rivers and Noret [[18]Rivers I. Noret N. Potential suicide ideation and its association with observing bullying at school.J Adolesc Health. 2013; 53: S32-S36Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar] report that students who observed bullying behavior were significantly more likely than those uninvolved in bullying to report symptoms of interpersonal sensitivity (feelings of being hurt and feelings of inferiority) and greater helplessness. However, the papers in this issue also convey the complexity of the relationship between bullying and suicide-related behaviors. In Espelage and Holt's work [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar], after controlling for delinquency and depression there was no increased risk of suicide-related behaviors for perpetrators; the increased risk did remain for victims. Klomek's [[19]Klomek A.B. Kleinman M. Altschuler E. et al. Suicidal adolescents' experiences with bullying perpetration and victimization during high school as risk factors for later depression and suicidality.J Adolesc Health. 2013; 53: S37-S42Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar] comparison of young people with bullying involvement and psychiatric symptoms (depression, suicidality, or substance use) at an initial screen to those with psychiatric symptoms but no bullying involvement found, at 2-year follow-up, that only perpetrators of bullying were significantly more likely to be functionally impaired than bullying-uninvolved students. In King's study of hospitalized suicidal youth, those who reported perpetrating bullying were more likely than uninvolved youth to have severe suicidal thoughts and psychosocial impairment, and to abuse substances. However, at 12-month follow-up, only the difference in psychosocial impairment remained. Interestingly, over the course of 1-year treatment for the suicidality, the rate of bullying perpetration declined [[20]King C.A. Horwitz A. Berona J. Jiang Q. Acutely suicidal adolescents who engage in bullying behavior: 1-year trajectories.J Adolesc Health. 2013; 53: S43-S50Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. In Karch's analysis of suicide fatalities among youth, bullying involvement was one of a myriad of factors precipitating a death by suicide. A quarter of young suicide victims had school problems, but only 12.4% of these school problems were attributed to bullying [[21]Karch D.L. Logan J. McDaniel D.D. et al. Precipitating circumstances of suicide among youth aged 10–17 years by sex: Data from the National Violent Death Reporting System, 16 States, 2005–2008.J Adolesc Health. 2013; 53: S51-S53Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar]. Other salient circumstances included depressed mood and/or other current mental health problems (37%); intimate partner problems (25%); history of suicide attempts (18%); and substance abuse problems (16%). Suicide attempts and substance use were risk factors that co-occurred with suicide ideation in Borowsky et al. as well [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all groups (victims, perpetrators, and bully-victims) a history of self-harm within the prior year and greater emotional distress (feelings of sadness, hopelessness, worry, stress, or pressure) drastically increased risk for suicide. For victims and bully-victims, a history of sexual abuse, a mental health problem, or running away from home in the past year increased the likelihood of suicidal thinking or behavior [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. More than half of the youth who were bully-victims and who expressed suicidal ideation or reported making an attempt also witnessed family violence, had a history of physical abuse, smoked cigarettes, used marijuana, skipped school because of safety concerns, or carried a weapon at school. Youth who were involved in bullying and reported suicide-related thoughts or behaviors also had higher mean scores for distractibility/impulsivity and lower mean scores for parent connectedness, connectedness to other adults, perceived caring by teachers, perceived caring by friends, liking school, academic achievement, physical activity, perceived school safety, and perceived neighborhood safety [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all three bullying-involved groups, parent connectedness (feeling like you can talk to mom/dad about problems; that mom/dad care about you) was protective for suicidal ideation and attempts. Other protective factors for victims included stronger connections to nonparental adults, stronger perceived caring by friends, and liking school. For bully-victims, greater perceived caring by friends was also protective [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. That there is a relationship between bullying and depression and that this relationship may help to explain the relationship between bullying and suicide is fairly consistent across papers. However, the direction of this relationship is unclear. Do youth who are bullied become depressed or are depressed youth more likely to be bullied? A study from the Netherlands suggests the answer may be “both.” Researchers found that victims of bullying had significantly higher chances of developing new psychosomatic and psychosocial problems over the course of a school year compared with children who were not bullied. However, children with preexisting depressive symptoms or anxiety were also significantly more likely to be newly victimized over the course of the school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. Despite the complexity of the relationship between bullying and suicide, there is no doubt that bullying involvement can have detrimental effects and prevention of bullying could improve health and mental health outcomes for many youth. The findings in these articles underscore the complexity of the relationship between bullying and suicide. A critical difference distinguishes an association between bullying and suicide from a causal relationship, with significant implications for prevention. Conveying that bullying alone causes suicide at best minimizes, and at worst ignores, the other factors that may contribute to death by suicide. This neglect may result in too narrow a focus of preventive action. We echo the call made by others for an integrated approach to preventing suicide and youth violence by focusing on shared risk and protective factors including individual coping skills, family and school social support, and supportive school environments [[22]Lubell K.M. Vetter J.B. Suicide and youth violence prevention: The promise of an integrated approach. Aggression and Violent Behavior. 2006; 11: 167-175Crossref Scopus (71) Google Scholar]. Strengthening social connectedness and ensuring access to supportive adults may pay dividends in impacting both bullying and suicide behaviors. Supportive home and school environments where young people feel connected are just one overlapping protective factor. Borowksy's findings regarding connection to parents, other adults, school, and friends reflect the need for multiple strategies that focus on both the school and home environments and that move beyond the individual skill-building level to foster supportive environments [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. The case for a supportive environment on bullying and suicide prevention is supported by Hatzenbuehler's work. In the paper contained in this special issue, he reports findings that lesbian and gay youths living in counties with fewer school districts with antibullying policies that specifically mentioned sexual orientation as a protected group were nearly two times more likely to have attempted suicide in the past year compared with those living in counties where more districts had these policies [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. Williams and Guerra reported that youth who describe their school climate as being trusting, fair, and pleasant have lower involvement in verbal, physical, and Internet bullying perpetration [[23]Williams K.R. Guerra N.G. Prevalence and predictors of internet bullying.J Adolesc Health. 2007; 41: S14-S21Abstract Full Text Full Text PDF PubMed Scopus (669) Google Scholar]. As reflected in CDC's strategic direction on suicide [[24]Centers for Disease Control and Prevention (CDC). Connectedness as a strategic direction for the prevention of suicidal behavior. Available at: http://www.cdc.gov/violenceprevention/pdf/suicide_strategic_direction-one-pager-a.pdf. Google Scholar], approaches intended to build connections between youth and school and home environments, as well as communities, are essential to suicide prevention. Sources of Strength is a school-based suicide-prevention program that trains youth opinion leaders to change the norms and behaviors of their peers by conducting well-defined messaging activities with adult mentoring, as well as increasing perceptions of adult support for suicidal youths and the acceptability of seeking help M. et of the Sources of Strength suicide prevention program by leaders in high J Health. 2010; PubMed Scopus Google Scholar]. work also the of connections to support prevention. As an example, the youth suicide prevention found that who reported a stronger connection to youth in their program were as likely to suicidal youth. the research also that the bullying prevention are A of school bullying strategies that school approaches that included multiple and at of school more often reduced victimization and bullying than the that only included or social groups A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. there is about the prevention of bullying and suicide, there is also do not studies over the past two have the of bullying prevention However, studies have in the States, these have not A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. is evidence that youth violence prevention that for such as and also rates of bullying The impact of and on bullying and A Pediatr Adolesc Med. PubMed Scopus Google Scholar]. More work is to strategies that bullying from among youth in the In that depression is a significant risk for bullying and suicide as well as a of other behaviors. We need to to mental among young people and their and to do in and However, the and impact of bullying, it is to move while these strategies are being We can by and strategies that have at increasing protective factors and risk factors associated with both bullying and suicide. is not that bullying in is it that bullying occur in the in and health their focus beyond just to those who are involved in bullying or suicide-related behaviors, but also in strategies to bullying and suicidal behavior from in the

Journal of Adolescent Health · editorial or comment · 170 citationsread the source →

Spirituality and mental health

INTRODUCTION All along, the majority position of Psychiatry has been that Psychiatry has nothing to do with religion and spirituality. Religious beliefs and practices have long been thought to have a pathological basis, and psychiatrists over a century have understood them in this light. Religion was considered as a symptom of mental illness. Jean Charcot and Sigmund Freud linked religion with neurosis. DSM3 portrayed religion negatively by suggesting that religious and spiritual experiences are examples of psychopathology. But recent research reports strongly suggest that to many patients, religion and spirituality are resources that help them to cope with the stresses in life, including those of their illness. Many psychiatrists now believe that religion and spirituality are important in the life of their patients. The importance of spirituality in mental health is now widely accepted. As John Turbott[1] puts it, rapprochement between religion and psychiatry is essential for psychiatric practice to be effective. The Royal College of Psychiatrists, London, has a special group on Psychiatry and Spirituality. The American College of Graduate Medical Education mandates in its special requirements for residency training in Psychiatry, that all programs must provide training in religious and spiritual factors that can influence mental health. The World Psychiatric Association recently established a section on psychiatry and religion. Lukoff et al.[2] proposed that the diagnostic entities of religious and psychospiritual problems should be incorporated in DSM4 which has been accepted. DSM4, V 62.89 includes three categories—normal religious and spiritual experiences; religious and spiritual problems leading to mental disturbances; and mental disturbances with a religious and spiritual context. I understand that the Indian Psychiatric Society has formed a task force on spirituality and mental health which is urging the Medical council of India to include taking the spiritual history as part of psychiatric evaluation. Even so the importance of religion and spirituality are not sufficiently recognized by the psychiatric community. Religion does not have a place in most of the psychiatry text books. Only very few psychiatrists make use of religion and spirituality in the therapeutic situation. This paper makes an attempt to bring out the importance of spirituality in mental health. WHAT IS SPIRITUALITY? Spirituality is a globally acknowledged concept. It involves belief and obedience to an all powerful force usually called God, who controls the universe and the destiny of man. It involves the ways in which people fulfill what they hold to be the purpose of their lives, a search for the meaning of life and a sense of connectedness to the universe. The universality of spirituality extends across creed and culture. At the same time, spirituality is very much personal and unique to each person. It is a sacred realm of human experience. Spirituality produces in man qualities such as love, honesty, patience, tolerance, compassion, a sense of detachment, faith, and hope. Of late, there are some reports which suggest that some areas of the brain, mainly the nondominant one, are involved in the appreciation and fulfillment of spiritual values and experiences.[3–5] SPIRITUALITY AND RELIGION Religion is institutionized spirituality. Thus, there are several religions having different sets of beliefs, traditions, and doctrines. They have different types of community-based worship programs. Spirituality is the common factor in all these religions. It is possible that religions can lose their spirituality when they become institutions of oppression instead of agents of goodwill, peace and harmony. They can become divisive instead of unifying. History will tell us that this had happened from time to time. It has been said that more blood has been shed in the cause of religion than any other cause. The medieval holy wars of Europe; the religion-based terrorism and conflicts of modern times are examples. We must remember that the institutions of religion are supposed to help us to practice spirituality in our lives. They need periodical revivals to put spirituality in place. SPIRITUAL DIMENSION IS IMPORTANT IN MENTAL HEALTH Mental health has two dimensions—absence of mental illness and presence of a well-adjusted personality that contributes effectively to the life of the community. Ability to take responsibility for one's own actions, flexibility, high frustration tolerance, acceptance of uncertainty, involvement in activities of social interest, courage to take risks, serenity to accept the things which we cannot change, courage to change the things which we can change, the wisdom to know the difference between the above, acceptance of handicaps, tempered self-control, harmonious relationships to self, others, including Nature and God, are the essential features of mental health. Spirituality is an important aspect of mental health. St. Augustine prayed “O God, thou created us in thy image and our hearts will be restless until they find their rest in Thee.” Though Sigmund Freud looked upon religion as an illusion and neurosis, Carl Jung considered the psyche as a carrier of truth, powerfully rooted in the unconscious mind. Religion is important, directly and indirectly, in the etiology, diagnosis, symptomatology, treatment and prognosis of psychiatric disturbances. Lack of spirituality can interfere with interpersonal relationships, which can contribute to the genesis of psychiatric disturbance. Psychiatric symptoms can have a religious content. For example, the loss of interest in religious activities is a common symptom of depression. Too much and distorted religious practices are common in schizophrenia. It is well recognized that some religious states and experiences are misdiagnosed as symptoms of psychiatric illness. Visions and possession states are examples. The spiritual background of the patient will help in the diagnosis of psychiatric disturbance. They are important in the treatment of psychiatric disturbance because spiritual matters can be profitably incorporated in psychotherapy. Spirituality is important in the prognosis of psychiatric conditions. In the spiritual perspective, a differentiation must be made between cure and healing. Cure is the removal of symptoms. Healing is the healing of the whole person. Adversity often produces maturity. Hence in psychotherapy, the patient must be helped to accept the handicap and transform the handicap to a life of usefulness. SOME SIGNIFICANT CLINICAL AND RESEARCH FINDINGS Recent studies show that religious beliefs and practices are supportive to cope with stresses in life and are beneficial to mental health. Thomas Ashby Wills,[6] Professor of Epidemiology and population health at Albert Einstein College of Medicine developed a scale that determines how important is religion to people. This was administered to 1182 children in New York. It was found that religiosity kept children from smoking, drinking and drug abuse by buffering the impact of life stresses. Gene H. Brody,[7] a research professor of child and family development at the University of Georgia, Athens, found that parents who were more involved in church activities were more likely to have harmonious marital relationships and better parenting skills. That in turn enhanced children's competence, self-regulation, psychosocial adjustment and school performance. Miller et al.[8] made a 10-year follow up study on depressed mothers and their offsprings and reported that maternal religiosity and mother-child concordance in religiosity were protective against depression in the offspring. They also reported that low level of religiosity was associated with substance abuse in the offsprings.[9] J. Scott Tonigan,[10] a research professor of psychiatry at the University of New Mexico, followed up 226 patients of alcohol dependence and reported that spirituality predicts behavior such as honesty and responsibility which in turn promoted alcohol abstinence. Wagner and King[11] conducted a study involving three groups—one group of patients who had psychotic illness, one group of formal care givers, and a third group of informal caregivers. The existential needs were the most important for the patient group, while the other groups considered material needs such as housing and work as more important. Neeleman and King[12] surveyed the psychiatric practices of 231 psychiatrists in London. 73% had no religious affiliation, 28% had belief in God, 61% believed that religion can protect against mental illness, and 48% asked patients about their religious practices. Baetz et al.[13] surveyed 1204 psychiatrists and 157 psychiatric patients in Canada. 54% of psychiatrists believed in God, 47% asked patients regarding their religious beliefs, and 55% consulted clergy for the management of patients. Among the patients, 71% believed in God, and 24% preferred psychiatrists who were religious. In an Australian survey, a large majority of patients with psychiatric illness wanted their therapists to be aware of their spiritual beliefs and needs and believed that their spiritual practices helped them to cope better.[14] Mathai and North[15] constructed a questionnaire, consisting of 5 questions and gave it to 70 parents of children attending child and adolescent mental health clinic. They reported that majority of the parents believed that spiritual concerns were important and that therapists should consider their spiritual beliefs in the management of the problems of the children. In USA, Curlin et al.[16] conducted a study of psychiatrists and compared them with physicians from other specialities in their religious affiliations and found that psychiatrists showed less religious affiliations. Several empirical studies on psychiatrists' religious characteristics have indicated that psychiatrists are significantly less religious than the general population, their patients and other physicians.[17],[18] In a 12-year follow up of all articles appearing in American Journal of Psychiatry and Archives of General Psychiatry, 72% of the religious commitment variables were beneficial to mental health; participation in religious services, social support, prayer and relationship with God were beneficial in 92% of citations.[19] Similar findings were reported in a review of the Journal of Family Practice.[20] In a British epidemiological study, church going and active religion were found to be protective to vulnerability for depression by Brown and Prudo.[21] In a detailed study on suicide in Netherlands, Kerkoff [quoted by Sims[22]] reported that there was a decline in suicidal rate, which was concurrent with a religious revival. A study on the factors in the course and outcome of schizophrenia was conducted in the Department of psychiatry, Christian Medical College, Vellore.. It was a collaborative study among three centers—Vellore, Madras and Lucknow. A two-year and five-year follow up showed that those patients who spent more time in religious activities tended to have a better prognosis.[23],[24] The above reports strongly suggest that religious beliefs and practices of psychiatric patients should be given importance. The sense of hope and spiritual support that patients get by discussing religious matters help them to cope better. They also suggest that the importance of religion and spirituality is not sufficiently recognized by the psychiatric community. Mental health workers must take it seriously since psychiatry cannot afford to ignore the importance of spirituality and religion in psychiatry. Sims[22] gives two case histories which drives home this fact. One is the case of Jim who suffered from Korsakov's psychosis. He was so deteriorated that he mistook his wife for a hat. In the ward, others considered him as desolate individual. But his behavior in the chapel was normal. In absolute concentration and attention, he would partake Holy Communion. He did not forget anything nor did he show any signs of Korsakov's psychosis. The other patient had chronic schizophrenia. He used to hear a voice commanding him to jump out of the window. His simple devout mother had taught him to resist the voice by praying to God. His mind was destroyed, but the capacity for spiritual life was present. Unfortunately, on the final occasion, he was too late to pray and he lost his life. Sims makes a comment, “It is unfortunate that we as psychiatrists can be so crass as to neglect this area of life which is clearly important to many of our patients.” Andresen,[25] in an editorial, has pointed out that our civilization's “loss of soul” may cause psychiatric symptoms such as depression, obsessions, addictions, and violence. She has suggested that it is the responsibility of psychiatrists to remind the medical fraternity the necessity of putting back the soul in medical ethics and the fact that spirituality is of vital importance for the mental health of people. WHAT CAN WE DO? As pointed out earlier, spiritual values and religious practices are important in the lives of our patients. Many of their problems may centre round existential preoccupations. It is therefore important that we incorporate spirituality and religious practices in our treatment protocol. We must propagate the Bio-psycho-socio-spiritual model in our approach in psychiatry. Harold Koening,[26] in his paper Religion and Mental health: what should psychiatrists do?, has made some suggestions in this area. Psychiatric history should be catered to the patients' spiritual orientation and religious practices. When we take psychiatric history, we usually ask for the denomination the patient belongs. We do not try to find out how the patient experiences religion. What does religion and spirituality mean to the patient. The psychiatric history should gather information about patient's religious background and experiences in the past and what role religion plays in coping with life stresses. Has patient had any past negative religious experiences? Has he got spiritual and social support from the congregation which he attends? How active is he in the religious congregation? Some religious beliefs can be in conflict with the proposed treatment. Some religious groups are against any type of treatment. Some religious conflicts and frustrations may be contributing to the present psychiatric problem. Sexual abuse by religious workers, traumatic events which turned the patient away from religious beliefs and activities, unanswered prayers, etc. are examples. There are some questionnaires that can be used to take a history of spirituality and religious experiences.[152728] Discussion with the patient on spiritual matters and religious experiences will strengthen the therapeutic relationship. It can also lead to reversal effect of a personal growth of the therapist. We should respect and support patients' religious beliefs if these help them to cope better or do not adversely affect their mental health. For example, if a patient says that his discipline of fasting and prayer helps him to cope better, then this has to be encouraged. We should also challenge the beliefs that can adversely affect mental health. This has to be done very tactfully. It is better to be neutral till we understand the patients and the issues involved well and a good therapeutic relationship is formed. Patients may wish to discuss with the therapist regarding their subjective experiences and existential needs. We should spend time in listening to them. Partnership with the religious workers is an useful area. Leavy and King[29] in their paper, The devil in the detail: partnership between psychiatry and faith based organizations, brings out the importance of such a partnership. They have reported that in UK, the clergy continue to have a central role in several communities and the utility of their involvement in the care of people with mental health problems is increasing. They have argued the importance of examining the form and parameters of partnership between the mental health team and the faith-based communities. For this partnership to be effective, the mental health workers must be spiritually oriented and the religious workers must be better informed about mental health and illness. As referred to earlier, some religious experiences are often misdiagnosed as symptoms of mental illness and vice versa, some psychiatric symptoms are explained as spiritual experiences. According to Sims,[22] phenomena such as faith, prayer and magic can lend themselves to description and definition using Jasperian phenomenology which can lead to a clear differentiation of normal and pathological religious experiences. This emphasizes the importance of psycho-pastoral partnership. One example of such a partnership is the Bangalore psycho-pastoral association, which runs a very efficient half-way home for psychiatric patients. Recognizing the importance of this, the World Council of Churches has formed an Advisory group on mental health and faith communities, which has been active in the exploration of strategies for an effective partnership between mental health services and faith communities. There can be problems in such a partnership. The religious workers may be reluctant to get involved in secular programs, leaving their spiritual fortress. Some of them can have incorrect ideas about the causes of mental illness, which can interfere with the treatment program. Some others can be against medical treatment. Mental health workers can also be prejudiced against the patients' religious beliefs and practices. As referred to earlier, research findings suggest that majority of psychiatrists do not give importance to the spiritual and religious experiences of patients. According to Neelman and Persaud,[30] this may be due to the following factors. Psychiatrists are by and large less religious than other physicians; psychiatrists often come to know of spirituality through the pathological religious symptoms of patients, which make them prejudiced against spirituality; psychiatrists tend to have a biological approach to mental illness, which ignores spiritual dimension; and psychiatrists may think that religion and spirituality cause dependence and guilt feelings. All these can be minimized with dialogue and periodical orientation programs. As John Turbott[31] puts it, psychiatry as a whole can only benefit if the concepts and vocabulary of religion and spirituality are more widely known and discussed among its practitioners. It is also true that conflicts and problems arise more with religious experiences and not with spirituality Praying with the patient is a controversial area. Many psychiatrists will argue that it is a dangerous ground upon which to tread. If at all it is done, it should be done only after a strong therapeutic relationship is established and only if the patient asks for it. Praying for the patient can be beneficial. Research. Although there is substantial body of literature that describes the connection between mental health and spirituality, we must develop theoretical models to understand their relationship in practice. The statistical findings reported earlier were mainly the results of surveys. High-quality evidence-based research is required to make the clinical applications more objective and effective. There are ample opportunities to do research in this area. Phenomena such as meditation, religious faith, and concepts are all What are their to normal life and psychiatric What are the which influence spiritual experiences? If spirituality is to mental health and if religious beliefs and experiences are important in the life of the psychiatric it is only that we should include religious concepts in psychotherapy. For example, some and can be profitably used to help the patient to cope with life situation. The spiritual concepts are incorporated in the treatment of out of the to spirituality. describes a which is called This is a treatment spiritual values to behavior which was developed and promoted at the University of areas are meaning and purpose and The patient is through to meaning and This with examining the of life such as and the patient to the patient is to the of of and in life. The the patient's that and and The involves a on after examining and one's in life. meaning is by meaning for each This is by and factors life and illness The are of and The use of meditation, and with of beliefs and on symptoms form the of the treatment. When the patient negative is the treatment about each about The are depression and adolescent show that produces

Indian Journal of Psychiatry · editorial or comment · 106 citationsread the source →

Post-traumatic growth after head injury: a long-term follow-up.

Primary objective: To investigate the time course of any positive psychological changes after traumatic brain injury (TBI) by comparing questionnaire responses in two groups of TBI survivors, early, 1-3 years post-injury and late, 10-12 years post-injury. Research design: A cross-sectional, between-group design. Method and procedure: TBI survivors were selected from the Reading Head Injury out-patient records by date of registration, early survivors from 2002-2004 and late survivors from 1993-1996 and sent a battery of postal questionnaires. These included The Post-traumatic Growth Inventory, The Life Satisfaction Checklist and The Hospital Anxiety and Depression Scale. Individuals were also given the opportunity to answer questions about their perception of their condition and to provide free text responses to reflect best and worst advice received, to describe positive and negative changes in themselves and to identify their most useful coping strategies. Results: 61 'early' and 65 'late' people were contacted with study details and 52 consented to the study, receiving questionnaires which provided 23 'early' and 25 'late' responses. There was a significantly greater degree of post-traumatic growth, as measured on 'The Post-traumatic Growth Inventory', reported by the later group (*p = 0.000), but no other significant differences between the groups in terms of all the other variables. Both groups reported greater life satisfaction pre-injury. Conclusion: Measures of Post-traumatic Growth (Relating to Others, Personal Strength, New Possibilities, Appreciation of Life and Spirituality) appear to increase over time after head injury. This is a positive message that clinicians should note and reinforce and could help to shape future adjustment.

Brain injury · 45 citationsread the source →

Maternal depression and child development

Maternal depression is considered a risk factor for the socioemotional and cognitive development of children [1]. The current prevalence of depression in Canada averages at 6%, which is similar to the rates in other western countries [2] (the female-to-male ratio average is 2:1 [3]). However, the prevalence of postpartum depression is approximately 13% [4]. Women of childbearing age are particularly at risk for depression, and many of them experience high levels of social morbidity and depressive symptoms that are often unrecognized and untreated. Mothers already at risk for depression are particularly fragile during the first months postpartum. Maternal depression has consequences on the child’s development. Because physicians who care for infants and children encounter mothers repeatedly, it is important that they have the knowledge and skills for the detection of symptoms of maternal depression. The objectives of this statement are: To review the present knowledge on the consequences of maternal depression on the development of children at various ages; To review the evidence-based literature on the treatment of maternal depression and its impact on newborns, infants and children; and To review the role of the child’s physician in the detection of symptoms of maternal depression, and the coordination of appropriate support and management. A literature search for the past 15 years was conducted using the MEDLINE database, and by reviewing the bibliographies of the retrieved articles. Of particular interest were the prospective longitudinal cohort studies in which mothers were recruited during their pregnancy or postpartum period, and the children were assessed at regular intervals. Postpartum psychiatric disorders are generally divided into three categories: postpartum blues, postpartum psychosis and postpartum depression. Postpartum blues is a relatively common emotional disturbance with crying, confusion, mood lability, anxiety and depressed mood. The symptoms appear during the first week postpartum, last for a few hours to a few days and have few negative sequelae. At the other end of the spectrum, postpartum psychosis refers to a severe disorder beginning within four weeks postpartum, with delusions, hallucinations and gross impairment in functioning. Postpartum depression begins in or extends into the postpartum period and core features include dysphoric mood, fatigue, anorexia, sleep disturbances, anxiety, excessive guilt and suicidal thoughts [5]. The diagnosis requires that symptoms be present for at least one month and result in some impairment in the woman’s functioning [6]. Women who have experienced postpartum depression have a 50% to 62% risk for future depressions [7]. Other risk factors for postpartum depression include a history of mood disorders, depression symptoms during the pregnancy and a family history of psychiatric disorders [4]. Stress factors, such as negative life events, poor marital relationships, having a special needs infant or medically ‘fragile’ infant, lack of social support, drug abuse, and personal and family psychopathology, have been associated with postpartum depression in some studies, but other studies have found no association [6]. Postpartum depression tends to be milder than episodes of depression that occur at other times, with lower levels of anxiety, agitation, insomnia and somatic symptoms [8]. However, the duration seems to be the same in postpartum and nonpostpartum depression, and lasts several months [6]. The consequences on the child of maternal postpartum depression are not restricted to infancy, but can extend into toddlerhood, preschool age and even school age. Maternal depression that occurs later influences the development of the school-age child and the adolescent. Table 1 summarizes the consequences of maternal depression from prenatal issues to adolescence. Consequences of maternal depression Consequences of maternal depression The associations between maternal depression, maternal behaviour and child outcomes are complex, and not all studies have found a relationship between maternal depression and indicators of poor parenting. Variations in the type, severity, chronicity and timing of maternal depression [9], heterogeneity in sampling (community versus high-risk multiproblem samples), and potentiating risk factors, such as family adversity, low social support and financial stress [10], all contribute to differences in outcomes in children. On the other hand, stress factors can be responsible for adverse child outcomes in the absence of maternal depression. On a daily basis, infants repeatedly participate in interactive routines with their mothers. Maternal depression compromises the dyad’s capacity to mutually regulate the interaction, through two interactive patterns, intrusiveness or withdrawal. Intrusive mothers display a hostile affect, and disrupt the infant’s activity. The infants experience anger, turn away from the mother to limit her intrusiveness and internalize an angry and protective style of coping. Withdrawn mothers are disengaged, unresponsive, affectively flat and do little to support the infant’s activity. The infants are unable to cope or self-regulate this negative state, and develop passivity, withdrawal and self-regulatory behaviours (eg, looking away or sucking on thumb) [11],[12]. Infants of postnatally depressed mothers have been reported to show patterns of dysregulated attention and arousal. In a study by Murray [13], cognitive performance regarding the independent existence of objects was worse for infants of 61 postnatally depressed mothers than the infants of 42 nondepressed mothers, even after adjustment for contextual adversity. Depressed mothers are less likely to offer contingent stimulation to their infants [14], and this disrupts their performance on nonsocial learning tasks [15]. Another factor that may interfere with learning is the negative affect shown by infants of depressed mothers, even when they are interacting with nondepressed adults [16]. It has been documented that an infant’s own negative affect interferes with learning and the ability to process information [17]. Depressed mothers generally show less attentiveness and responsiveness to their children’s needs. They are also poor models for negative mood regulation and problem solving. Longitudinal studies have compared the behaviours of depressed and nondepressed mothers, and the outcome of their children. They showed that depressed mothers were less likely to set limits on their children and to follow through if they did set limits [18]. Children of depressed mothers appeared more passively noncompliant, with less mature expressions of age-appropriate autonomy [19]. They were rated by their dysphoric mothers as being more vulnerable, and having more internalizing (depressed) and externalizing problems (aggressive and destructive), which are associated with lower interaction ratings [20]. They were also more likely to respond negatively to friendly approaches, more likely to engage in low-level physical play and less likely to engage in individual creative play than control children [21]. These aspects of child behaviour were associated with postnatal depression, even when taking adverse situations such as marital conflict, and demographic variables, such as maternal age, ethnicity, socioeconomic status, marital status, child’s age and number of siblings, into account. Studies on large samples all agree on the negative impact of maternal postpartum depression on a child’s cognitive development. Early experience with insensitive maternal interactions (as in maternal postpartum depression) appears to be predictive of poorer cognitive functioning [22]. Boys may be more sensitive than girls to the effects of the mother’s illness. In a study by Sharp et al [23], only boys showed a decrease on standardized tests of intellectual attainment (mainly on indexes of abstract intelligence, reasoning about opposites and analogies) and the “draw-a-child” task. Other aspects of cognitive development, such as cognitive-linguistic functioning [24], have also been shown to be negatively affected, and there were also deficits on the perceptual and performance scale [25]. Outcome effects were independent of birth order, maternal education, family income, marital status and social support. Various studies have shown that school-age children of depressed mothers display impaired adaptive functioning, including internalizing and externalizing problems. Although the studies reviewed by Beardslee et al [26] were uncontrolled studies, a more recent review by Downey and Coyne [27] included studies using control groups (matched for age of parents, occupational status, ethnicity, marital status, and number and age of children), standardized diagnostic criteria to identify parental depression and valid measures of psychological functioning in children. Billings and Moos [28] showed that family stress and low support added to the prediction of child disturbance beyond that accounted for by having a depressed parent. However, the study of Lee and Gotlib [29] comparing children of depressed psychiatric mothers and nondepressed psychiatric mothers showed that the child’s adjustment was more strongly related to the severity of maternal psychopathology than to diagnosis status. Children of depressed parents are also at higher risk of psychopathology, including affective (mainly depression), anxiety and conduct disorders. Hammen et al [30] compared children from four groups of mothers (mothers with unipolar disorder, bipolar disorder and chronic medical illness, and normal mothers) with no differences in ethnicity, age, socioeconomic status or educational level. They showed that, even with the effects of chronic stress statistically controlled, there were still differences in the psychosocial outcome variables among groups, and there was particular impairment in children of unipolar mothers [30]. Other studies [31]–[34], in which there were no demographic differences (age, marital status and socioeconomic level) between depressed and nondepressed parents, have confirmed an increased risk of psychopathology in the children of depressed parents. It seems that onset of a major depression disorder before 30 years of age in parents increases the risk of their children developing depression quite early during childhood [33],[34]. It is somewhat difficult to delineate which behavioural disorders are due to maternal depression and other environmental factors, and which are due to genetic susceptibility. There seems to be an association between attention deficit/hyperactivity disorder (ADHD) in children and maternal mental health, as shown by a cross-sectional study by Lesesne et al [35]. Using the 1998 National Health Interview Study on 9529 mother-child dyads, they found an association between an activity-limiting depression, anxiety or emotional problem in mothers, and ADHD in their children aged four to 17 years, even after adjusting for the child’s age, sex, race, household income and type of family structure [35]. In a longitudinal study of 132 children by Hay et al [36], lower IQ scores, attentional problems, difficulties in mathematical reasoning and special educational needs were significantly more frequent in children whose mothers were depressed at three months postpartum than in controls. In addition, boys were more affected than girls. However, academic difficulties in children of depressed mothers were not mediated by parental IQ, sociodemographic variables or the mother’s mental health after the postpartum depressive episode. Generally, adolescence is a vulnerable period for affective illness and major depressive disorder, which are observed twice as often in girls than in boys [37]. Two cross-sectional studies showed that adolescents with a depressed parent suffered from psychosocial maladjustment [38] and experienced a significantly higher rate of affective disorder than adolescents of nonaffective psychiatric control parents [39]. Longitudinal studies have consistently reported higher rates of major depression and other psychopathology (anxiety disorders, conduct disorders and substance abuse disorders) in adolescents with an affectively ill parent than in control families with similar demographic characteristics (age, ethnicity, socioeconomic status and educational level). Hammen et al [40] followed a cohort of 92 children/adolescents between the ages of eight and 16 years over a three-year They found that children/adolescents with mothers from unipolar depression higher rates of affective disorders, with frequent the disorders in children/adolescents with mothers from bipolar depression were less et al families with children between and years over a They observed higher rates of major depression, disorder and in the of depressed parents than in the major depression onset was between the ages of 15 and Beardslee et al at an of a health with children between the ages of and At the of the children/adolescents with an affectively ill parent at least one of an affective illness compared with in the control years the rates of affective disorders were and and of affectively ill parents onset and a number of in school-age ADHD and learning into adolescence [35]. It has been in many studies that some children with depressed do not display behavioural and that some factors may or the effects of parental depression contextual risk factors, marital life social support lower social and lower maternal are factors that may parental depression and parenting. In a study of mothers with major depressive disorder the child’s et al showed that contextual risk factors mediated the between maternal depression and child behaviour problems. The role of and in child development are to be on mothers, the for the infant is the However, in their study of to et al showed that infants of depressed mothers with their nondepressed who the effects of the mother’s depression on infant interaction In addition, a cross-sectional study of families with children between the ages of and years showed that in families in which the mother was children showed lower social and emotional if the also a psychiatric The role of has been in the of marital to a review by Downey and Coyne marital to children externalizing problems, and increases their risk for depression by and parental depression. differences have been in some studies with boys being more vulnerable and by maternal depression than girls. of the child also to the of parental depression. It has been shown that mothers more negative of their child’s less in their parental and more often A child with a more and be more to their depressed mother’s negative behaviour and not show a of Other of in children include social and cognitive skills that them attention from adults other than their depressed parents and their depressed of and It seems that an of the illness and by the child that or is not to for the behaviour is important to the development of in a child Although the interaction between parents and their child is beyond the of the present it has been that parents of children higher depression than control parents and that is a of maternal depression Because many depressive episodes occur during childbearing years, the to be between the mother’s and a who from depression with is at high risk of [7]. during pregnancy is associated with prenatal poor higher low birth substance abuse and The morbidity of depression during pregnancy be the risk of have been by that are associated with a low risk of and the However, et al did not in major or in taking compared with controls. Another study on taking showed an in when the was during the In the period, it seems that behavioural and rate to are in infants to in et al compared children of mothers with a during children of mothers with and control children of nondepressed mothers who did not during adjusting for the duration and severity of maternal depression, duration of number of depressive episodes after maternal IQ and socioeconomic status, the study showed that and no adverse effects on the IQ, development or behaviour of children between 15 and months of age In a et al compared children to depressed mothers who not to during pregnancy and children to mothers with Although the on the indexes were similar in groups of children to children to lower on the indexes and the factors of the of the of is the of It is important that a depressed mother who to be the is in the postnatal period, there is a risk of with negative consequences on the emotional and behavioural development of the On the other hand, all are in of the information from and to a review by and the and are the of or have been in children or through To infant when postpartum depressed mothers, it is important to all maternal of and and to the of environmental and maternal illness is interaction with the infant or other it is to on the of treatment it is to the of the be on the mother’s and experience of adverse effects with a particular risk of interactions with and adverse effects associated with a particular on mothers and their Maternal be to for the that control of the depressive is and the in pregnancy be in the postnatal The infant’s to can be by the of and it and approximately to after the mother has the Although there is no on the of during pregnancy and be considered in the of a as by the of et al be considered in who have to severe symptoms and who have not to show that and appear to be quite during pregnancy and the postnatal period, and may be during pregnancy and Because of the consequences of maternal depression on an infant’s development, many studies have postnatal mothers. have on the mother’s mood state, her to or of the infant’s and the negative about the infant’s behaviours [16]. to the of by mothers to their infants or by mothers to and their attention support and have been in depressed and as as their and development treatment have been an interactive treatment at problems by the mother in the of her infant that support, and education, with of depressed mothers and their a and in a infant over a period to of months mothers from the showed more interaction and their infants and scores, as as more interaction behaviours than in the control children and adolescents from families with a depressed parent may from a on about the illness within the family and on the development of in the In a study by Beardslee et al families who an to child and a parent with an affective disorder were to a or a parents information about the and symptoms of childhood and depression, and the for within the However, the cognitive to the life of the in the showed more behaviour and among parents and including higher levels of from parents to children about the illness and by the child of the affective illness et al compared with interaction The treatment on the mother’s of her infant and her relationship with the infant, and aspects of the mother’s own childhood and early already the interaction to identify behaviours and to of an infant’s a of there was a in The sleep and difficulties maternal to increased and control In addition, maternal and infants more less and showed more on and problems experienced by depressed postpartum mothers. In a study of depressed postpartum depressive symptoms and social adjustment in the compared with the control on the has also been in the of postpartum depression in with at least one risk factor for postpartum depression and are and is the in Canada seems to be for to depression, it has many drug interactions There are no on its and it be as during pregnancy on its during are a it was observed that was in at a low and the lower limit of in the infant’s A prospective study of found no differences in the of in over the first of life compared with a control to the of the on the Health to of for depression using the Health or the of of from the Health However, it is strongly that a high of for depression among their In their statement the adults for depression in that have in to treatment and of of In their for the of on the that the physical and mental health of the parents in their and review the of attention to their own mental health needs. In a of three et al reported that more than of mothers the impact of depression on the child’s health and and that more than of mothers the role in and to However, a recent study showed that maternal depression was by health care et al reported that in their ability to maternal depression and their of knowledge and The role in maternal depression be one of followed by for and There be a about family history of depression and about episodes of maternal depression. have been and to postpartum depression of that may information about postpartum depression are in Table depression is the can and with the mother’s physician or an appropriate to psychiatric between the mother’s physician and the child’s physician is to information about postpartum depression are about being a that is or difficult to care are in is the past have often been by depressed or the past have often been by having little interest or in are about being a that is or difficult to care are in is the past have often been by depressed or the past have often been by having little interest or in to information about postpartum depression are about being a that is or difficult to care are in is the past have often been by depressed or the past have often been by having little interest or in are about being a that is or difficult to care are in is the past have often been by depressed or the past have often been by having little interest or in many mothers, care may be their with health care The child’s physician may be the first to of the and difficulties of a the child’s physician can the depressed mother her mood affect her and contribute to the child’s problems. of include infant sleep problems, child social and family It is important to a high of of maternal depression when child behaviour problems are during a medical for the depression of the mother over behavioural for the Because postpartum depression can have effects on mothers and children and its prevalence occurs at approximately three it has been to for postpartum depression at the and care In school-age children and the of difficulties in child adjustment and impaired functioning at and in school the physician to the of maternal depression. in families with a history of depression, one in that may depressed or display other psychopathology, at adolescence. These often and for a for the The child’s physician has a role in to the appropriate for the and the parent. that children of depressed mothers are at risk for and behavioural problems, as as their for developing a depressive disorder the physician conduct regular of the offer and them early for more and of and behavioural disorders. Postpartum depression occurs in approximately 13% of and often it is there is often a of between and psychiatric and treatment of the lack of The infant of a depressed mother is at risk for developing negative affect and dysregulated attention and arousal. and of depressed mothers are at risk for developing poor internalizing and externalizing problems, and difficulties in cognitive functioning and in social interactions with parents and and children of depressed parents are at risk for impaired adaptive functioning and psychopathology, including conduct disorders, affective disorders and anxiety disorders. They are also at risk for ADHD and learning risk factors such as marital and life may parental depression and child behaviour problems. On the other hand, some children develop through an social cognitive skills and of the illness. with during pregnancy and is but no major or physical and to the or the infant have been The of the mother’s depression to the low of on the or the the of the and development of infants and the physician to of mother-child interaction and behavioural and problems in the such they in the of maternal depression, a few and with the mother’s physician or psychiatric Mothers who have during pregnancy be that of the to that there is no increased risk of or Mothers who have during pregnancy be about the of their child studies have not shown adverse for differences whose to be Mothers who have during be that of the to that there are no or in children to such through Mothers be that on are and that such not be during pregnancy and on of and of of The in this statement do not an of treatment or to be taking into individual may be are current at of

Paediatrics & Child Health · 312 citationsread the source →

Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities.

Purpose: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long-term unmet mental health, social, and vocational needs. This cross-sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE. Methods: Sixty-nine CAE children aged 9.6 (SD = 2.49) years and 103 age- and gender-matched normal children had semistructured psychiatric interviews, as well as cognitive and linguistic testing. Parents provided demographic, seizure-related, and behavioral information on their children through a semi-structured psychiatric interview and the child behavior checklist (CBCL). Results: Compared to the normal group, 25% of the CAE children had subtle cognitive deficits, 43% linguistic difficulties, 61% a psychiatric diagnosis, particularly attention deficit hyperactivity disorder (ADHD) and anxiety disorders, and 30% clinically relevant CBCL broad band scores. The most frequent CBCL narrow band factor scores in the clinical/borderline range were attention and somatic complaints, followed by social and thought problems. Duration of illness, seizure frequency, and antiepileptic drug (AED) treatment were related to the severity of the cognitive, linguistic, and psychiatric comorbidities. Only 23% of the CAE subjects had intervention for these problems. Conclusions: The high rate of impaired behavior, emotions, cognition, and language and low intervention rate should alert clinicians to the need for early identification and treatment of children with CAE, particularly those with longer duration of illness, uncontrolled seizures, and AED treatment.

Epilepsia · 260 citationsread the source →

Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study.

Background: Critical illness is associated with cognitive impairment, but mental health and functional disabilities in survivors of intensive care are inadequately characterised. We aimed to assess associations of age and duration of delirium with mental health and functional disabilities in this group. Methods: In this prospective, multicentre cohort study, we enrolled patients with respiratory failure or shock who were undergoing treatment in medical or surgical ICUs in Nashville, TN, USA. We obtained data for baseline demographics and in-hospital variables, and assessed survivors at 3 months and 12 months with measures of depression (Beck Depression Inventory II), post-traumatic stress disorder (PTSD, Post-Traumatic Stress Disorder Checklist-Event Specific Version), and functional disability (activities of daily living scales, Pfeffer Functional Activities Questionnaire, and Katz Activities of Daily Living Scale). We used linear and proportional odds logistic regression to assess the independent associations between age and duration of delirium with mental health and functional disabilities. This study is registered with ClinicalTrials.gov, number NCT00392795. Findings: We enrolled 821 patients with a median age of 61 years (IQR 51-71), assessing 448 patients at 3 months and 382 patients at 12 months after discharge. At 3 months, 149 (37%) of 406 patients with available data reported at least mild depression, as did 116 (33%) of 347 patients at 12 months; this depression was mainly due to somatic rather than cognitive-affective symptoms. Depressive symptoms were common even among individuals without a history of depression (as reported by a proxy), occurring in 76 (30%) of 255 patients with data at 3 months and 62 (29%) of 217 individuals at 12 months. Only 7% of patients (27 of 415 at 3 months and 24 of 361 at 12 months) had symptoms consistent with post-traumatic distress disorder. Disabilities in basic activities of daily living (ADL) were present in 139 (32%) of 428 patients at 3 months and 102 (27%) of 374 at 12 months, as were disabilities in instrumental ADL in 108 (26%) of 422 individuals at 3 months and 87 (23%) of 372 at 12 months. Mental health and functional difficulties were prevalent in patients of all ages. Although old age was frequently associated with mental health problems and functional disabilities, we observed no consistent association between the presence of delirium and these outcomes. Interpretation: Poor mental health and functional disability is common in patients treated in intensive-care units. Depression is five times more common than is post-traumatic distress disorder after critical illness and is driven by somatic symptoms, suggesting approaches targeting physical rather than cognitive causes could benefit patients leaving critical care. Funding: National Institutes of Health AG027472 and the Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System.

The Lancet. Respiratory medicine · 454 citationsread the source →