Search the source libraries

Effectiveness of workplace-based interventions to promote wellbeing among menopausal women: A systematic review.

Menopausal symptoms are known to affect quality of life and work productivity. This systematic review aimed to describe the range and effectiveness of workplace-based interventions for menopause. MEDLINE, PubMed, Embase, CINAHL, Cochrane Library, Web of Science, PsycINFO, EconLit, and SCOPUS were searched from the inception until April 2022. Quantitative interventional studies evaluating physical/virtual workplace-based interventions aiming to improve well-being, work, and other outcomes, that involved women in menopausal transition, or their line managers/supervisors were eligible for inclusion. Two randomized controlled trials and three uncontrolled trials, comprising 293 women aged 40-60 years and 61, line managers/supervisors, were included in the review. Results were narratively synthesized due to the heterogeneity of interventions and outcomes and we found that only a limited range of interventions have been evaluated for their ability to support women going through menopausal transition in the workplace. Self-help cognitive behavioural therapy (CBT); Raja yoga; and health promotion (involving menopause consultations, work-life coaching and physical training) improved menopausal symptoms significantly. Self-help CBT was associated with a significant improvement in mental resources for work, presenteeism, and work and social adjustment. Awareness programs significantly improved knowledge and attitudes of both employees and line managers/supervisors about menopause. The interventions have mostly been evaluated in small studies with selected populations but have improved menopausal symptoms and work outcomes. A customizable menopause wellbeing intervention package incorporating these evidence-supported interventions should be developed and implemented on a wider scale within organizations alongside robust evaluation of its effectiveness.

Post reproductive health · systematic review · 15 citationsread the source →

Decisional Satisfaction, Regret, and Conflict Among Parents of Infants with Neurologic Conditions.

Objective: To characterize decisional satisfaction, regret, and conflict among parents of critically ill infants with neurologic conditions. Study design: In this prospective cohort study, we enrolled parents of infants with neurologic conditions in the intensive care unit (ICU). Hospital discharge surveys included the validated Family Satisfaction with the ICU (FS-ICU) decision making subscale, Decision Regret Scale (DRS), and Decisional Conflict Scale (DCS). We defined high satisfaction with decision making as an FS-ICU score ≥75, high decisional regret/conflict as DRS/DCS score >25, and within-couple disagreement as a difference of at least 25 points between scores. Results: We enrolled 61 parents of 40 infants (n = 40 mothers, n = 21 fathers); 35 mothers and 15 fathers completed surveys. Most mothers reported high satisfaction with decision making (27 of 35; 77%) and low decision regret (28 of 35; 80%); 40% (14 of 35) reported high decisional conflict. Mothers and fathers reported higher decisional conflict in the domains of uncertainty and values clarity compared with the domain of effective decision making (Bonferroni-corrected P < .05). There were no differences in decision outcomes between paired mothers and fathers; however, within any given couple, there were numerous instances of disagreement (7 of 15 for decision regret and 5 of 15 for decisional conflict). Conclusions: Many parents experience decisional conflict even if they ultimately have high satisfaction and low regret, underscoring the need for decision aids targeting uncertainty and values clarity. Couples frequently experience different levels of decisional regret and conflict.

The Journal of pediatrics · 14 citationsread the source →

Feasibility and efficacy of a digital CBT intervention for symptoms of Generalized Anxiety Disorder: A randomized multiple-baseline study.

Background and objectives: Cognitive behavioral therapy (CBT) is a first-line treatment for anxiety, but it is not widely available as clinical guidelines recommend. We examined the feasibility and efficacy of a novel smartphone-based fully automated digital CBT intervention, 'Daylight™', to improve symptoms of Generalized Anxiety Disorder (GAD). Methods: In this multiple-baseline design, 21 adults (20 F; mean age 43yrs. range 19-65yrs.) with moderate-to-severe symptoms of GAD were randomized to one of three baseline durations (2-, 4-, or 6-weeks) and then received access to digital CBT. Participants completed daily ratings of anxiety and worry, weekly measures of anxiety, depressive symptoms, and sleep, and measures of anxiety, worry, wellbeing, quality of life, CBT skill acquisition, and work performance at initial assessment prior to baseline randomization, post-intervention, and follow-up. Results: Digital CBT was found to be feasible in terms of engagement, satisfaction, and safety. For preliminary efficacy, improvements were detected in daily and weekly outcomes of anxiety for most participants. Despite individual differences, significant improvements occurred with the introduction of digital CBT and not during baseline. Overall, 70% of participants no longer had clinically significant symptoms of GAD, 61% no longer had significant depressive symptoms, and 40% no longer had significant sleep difficulty at post-intervention. Limitations: The study sample was recruited using the internet and was mostly female, limiting the generalizability of the findings. Conclusions: Findings support the feasibility and efficacy of Daylight. Further examination in randomized controlled trials is now warranted.

Journal of behavior therapy and experimental psychiatry · randomised controlled trial · 24 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 →

Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation.

Background: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. Purpose: To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure. Data sources: MEDLINE and Cochrane databases through December 2014. Study selection: English-language systematic reviews, randomized trials, and observational studies of screening. Data extraction: Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus. Data synthesis: Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer-specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100,000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone. Limitations: Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models. Conclusion: False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely. Primary funding source: Agency for Healthcare Research and Quality.

Annals of internal medicine · systematic review · 267 citationsread the source →

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 →

Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis.

Background: Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder. Methods: For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features. Findings: We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21-3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25-1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10-2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45-5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39-2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41-2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13-1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43-2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45-2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09-1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07-1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88-2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality. Interpretation: Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder. Funding: None.

The lancet. Psychiatry · meta-analysis · 278 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 →

Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation.

Objective: High oxidative stress potentially leads to accelerated telomere shortening and consequent premature cell senescence, implicated in type 2 diabetes (T2D) development. Therefore, we studied the association of leukocyte telomere length (LTL) with the presence of T2D, as well as the effect on the patients' LTL of plasma oxidative stress and of variation in UCP2, a gene involved in the mitochondrial production of reactive oxygen species. Methods: Mean LTL was determined in 569 Caucasian, 103 South Asian and 70 Afro-Caribbean T2D patients aged from 24 to 92 years, 81 healthy Caucasian male students aged from 18 to 28 years and 367 healthy Caucasian men aged from 40 to 61 years by real-time PCR. Plasma total antioxidant status (TAOS) was measured in the T2D patients by a photometric microassay. The patients were also genotyped for the UCP2 functional variants -866G>A and A55V. Results: Afro-Carribeans had 510bp longer mean length compared to Caucasians (p<0.0001) and 500bp longer than South Asians (p=0.004). T2D subjects displayed shorter age-adjusted LTL compared to controls [6.94(6.8-7.03) vs. 7.72(7.53-7.9), p<0.001] with subjects in the middle and the lowest tertile of LTL having significantly higher odds ratios for T2D compared to those in the highest tertile [1.50(1.08-2.07) and 5.04(3.63-6.99), respectively, p<0.0001]. In the patients, LTL was correlated negatively with age (r=-0.18, p<0.0001) and positively with TAOS measures (r=0.12, p=0.01) after adjusting for age, while carriers of the UCP2 -866A allele had shorter age-adjusted LTL than common homozygotes [6.86(6.76-6.96)kb vs. 7.03(6.91-7.15)kb, p=0.04]. Conclusion: The present data suggest that shorter LTL is associated with the presence of T2D and this could be partially attributed to the high oxidative stress in these patients. The association of the UCP2 functional promoter variant with the LTL implies a link between mitochondrial production of reactive oxygen species and shorter telomere length in T2D.

Atherosclerosis · 220 citationsread the source →

The global contribution of invasive vertebrate eradication as a key island restoration tool.

Islands are global hotspots for biodiversity and extinction, representing ~ 5% of Earth's land area alongside 40% of globally threatened vertebrates and 61% of global extinctions since the 1500s. Invasive species are the primary driver of native biodiversity loss on islands, though eradication of invasive species from islands has been effective at halting or reversing these trends. A global compendium of this conservation tool is essential for scaling best-practices and enabling innovations to maximize biodiversity outcomes. Here, we synthesize over 100 years of invasive vertebrate eradications from islands, comprising 1550 eradication attempts on 998 islands, with an 88% success rate. We show a significant growth in eradication activity since the 1980s, primarily driven by rodent eradications. The annual number of eradications on islands peaked in the mid-2000s, but the annual area treated continues to rise dramatically. This trend reflects increases in removal efficacy and project complexity, generating increased conservation gains. Our synthesis demonstrates the collective contribution of national interventions towards global biodiversity outcomes. Further investment in invasive vertebrate eradications from islands will expand biodiversity conservation while strengthening biodiversity resilience to climate change and creating co-benefits for human societies.

Scientific reports · 42 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 →

Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial.

Background: The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China. Methods: In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 1010 viral particles, 1·6 × 1011 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively. Findings: Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 1010 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90 peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC90 titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group. Interpretation: The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease. Funding: Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.

The Lancet. Global health · randomised controlled trial · 76 citationsread the source →

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.

Background: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. Methods: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. Findings: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. Interpretation: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. Funding: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

The lancet. Diabetes & endocrinology · randomised controlled trial · 465 citationsread the source →

Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial.

Background: Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample. Methods: In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion. Results: Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point. Conclusions: This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.

Biological psychiatry · randomised controlled trial · 586 citationsread the source →

Experiential virtual scenarios with real-time monitoring (interreality) for the management of psychological stress: a block randomized controlled trial.

Background: The recent convergence between technology and medicine is offering innovative methods and tools for behavioral health care. Among these, an emerging approach is the use of virtual reality (VR) within exposure-based protocols for anxiety disorders, and in particular posttraumatic stress disorder. However, no systematically tested VR protocols are available for the management of psychological stress. Objective: Our goal was to evaluate the efficacy of a new technological paradigm, Interreality, for the management and prevention of psychological stress. The main feature of Interreality is a twofold link between the virtual and the real world achieved through experiential virtual scenarios (fully controlled by the therapist, used to learn coping skills and improve self-efficacy) with real-time monitoring and support (identifying critical situations and assessing clinical change) using advanced technologies (virtual worlds, wearable biosensors, and smartphones). Methods: The study was designed as a block randomized controlled trial involving 121 participants recruited from two different worker populations-teachers and nurses-that are highly exposed to psychological stress. Participants were a sample of teachers recruited in Milan (Block 1: n=61) and a sample of nurses recruited in Messina, Italy (Block 2: n=60). Participants within each block were randomly assigned to the (1) Experimental Group (EG): n=40; B1=20, B2=20, which received a 5-week treatment based on the Interreality paradigm; (2) Control Group (CG): n=42; B1=22, B2=20, which received a 5-week traditional stress management training based on cognitive behavioral therapy (CBT); and (3) the Wait-List group (WL): n=39, B1=19, B2=20, which was reassessed and compared with the two other groups 5 weeks after the initial evaluation. Results: Although both treatments were able to significantly reduce perceived stress better than WL, only EG participants reported a significant reduction (EG=12% vs. CG=0.5%) in chronic "trait" anxiety. A similar pattern was found for coping skills: both treatments were able to significantly increase most coping skills, but only EG participants reported a significant increase (EG=14% vs CG=0.3%) in the Emotional Support skill. Conclusions: Our findings provide initial evidence that the Interreality protocol yields better outcomes than the traditionally accepted gold standard for psychological stress treatment: CBT. Consequently, these findings constitute a sound foundation and rationale for the importance of continuing future research in technology-enhanced protocols for psychological stress management. Trial registration: ClinicalTrials.gov: NCT01683617; http://clinicaltrials.gov/show/NCT01683617 (Archived by WebCite at http://www.webcitation.org/6QnziHv3h).

Journal of medical Internet research · randomised controlled trial · 68 citationsread the source →

Exercise improves executive function and achievement and alters brain activation in overweight children: a randomized, controlled trial.

Objective: This experiment tested the hypothesis that exercise would improve executive function. Design: Sedentary, overweight 7- to 11-year-old children (N = 171, 56% girls, 61% Black, M ± SD age = 9.3 ± 1.0 years, body mass index [BMI] = 26 ± 4.6 kg/m², BMI z-score = 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 min/day), or a control condition. Main outcome measures: Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional MRI measured brain activity during executive function tasks. Results: Intent to treat analysis revealed dose-response benefits of exercise on executive function and mathematics achievement. Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity attributable to exercise was also observed. Conclusion: Consistent with results obtained in older adults, a specific improvement on executive function and brain activation changes attributable to exercise were observed. The cognitive and achievement results add evidence of dose-response and extend experimental evidence into childhood. This study provides information on an educational outcome. Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic, physical activity may prove to be a simple, important method of enhancing aspects of children's mental functioning that are central to cognitive development. This information may persuade educators to implement vigorous physical activity.

Health psychology : official journal of the Division of Health Psychology, American Psychological Association · randomised controlled trial · 469 citationsread the source →

A longitudinal, observational study of the features of transitional healthcare associated with better outcomes for young people with long-term conditions.

Background: Most evidence about what works in transitional care comes from small studies in single clinical specialties. We tested the hypothesis that exposures to nine recommended features of transitional healthcare were associated with better outcomes for young people with long-term conditions during transition from child-centred to adult-oriented health services. Methods: This is a longitudinal, observational cohort study in UK secondary care including 374 young people, aged 14-18.9 years at recruitment, with type 1 diabetes (n = 150), cerebral palsy (n = 106) or autism spectrum disorder with an associated mental health problem (n = 118). All were pre-transfer and without significant learning disability. We approached all young people attending five paediatric diabetes centres, all young people with autism spectrum disorder attending four mental health centres, and randomly selected young people from two population-based cerebral palsy registers. Participants received four home research visits, 1 year apart and 274 participants (73%) completed follow-up. Outcome measures were Warwick Edinburgh Mental Wellbeing Scale, Mind the Gap Scale (satisfaction with services), Rotterdam Transition Profile (Participation) and Autonomy in Appointments. Results: Exposure to recommended features was 61% for 'coordinated team', 53% for 'age-banded clinic', 48% for 'holistic life-skills training', 42% for 'promotion of health self-efficacy', 40% for 'meeting the adult team before transfer', 34% for 'appropriate parent involvement' and less than 30% for 'written transition plan', 'key worker' and 'transition manager for clinical team'. Three features were strongly associated with improved outcomes. (1) 'Appropriate parent involvement', example association with Wellbeing (b = 4.5, 95% CI 2.0-7.0, p = 0.001); (2) 'Promotion of health self-efficacy', example association with Satisfaction with Services (b = - 0.5, 95% CI - 0.9 to - 0.2, p = 0.006); (3) 'Meeting the adult team before transfer', example associations with Participation (arranging services and aids) (odds ratio 5.2, 95% CI 2.1-12.8, p < 0.001) and with Autonomy in Appointments (average 1.7 points higher, 95% CI 0.8-2.6, p < 0.001). There was slightly less recruitment of participants from areas with greater socioeconomic deprivation, though not with respect to family composition. Conclusions: Three features of transitional care were associated with improved outcomes. Results are likely to be generalisable because participants had three very different conditions, attending services at many UK sites. Results are relevant for clinicians as well as for commissioners and managers of health services. The challenge of introducing these three features across child and adult healthcare services, and the effects of doing so, should be assessed.

BMC medicine · cohort or longitudinal · 94 citationsread the source →

The Association Between Arterial Oxygen Tension and Neurological Outcome After Cardiac Arrest.

A number of observational studies have evaluated the association between arterial oxygen tensions and outcome after cardiac arrest with variable results. The objective of this study is to determine the association between arterial oxygen tension and neurological outcome after cardiac arrest. A retrospective cohort analysis was performed using the Penn Alliance for Therapeutic Hypothermia registry. Adult patients who experienced return of spontaneous circulation after in-hospital or out-of-hospital cardiac arrest (OHCA) and had a partial pressure of arterial oxygen (PaO2) recorded within 48 hours were included. Our primary exposure of interest was PaO2. Hyperoxemia was defined as PaO2 > 300 mmHg, hypoxemia as PaO2 < 60 mmHg, and optimal oxygenation as PaO2 60-300 mmHg. The primary outcome was neurological function at hospital discharge among survivors, as described by the cerebral performance category (CPC) score, dichotomized into "favorable" (CPCs 1-2) and "unfavorable" (CPCs 3-5). Secondary outcomes included in-hospital mortality. A total of 544 patients from 13 institutions were included. Average age was 61 years, 56% were male, and 51% were white. A total of 64% experienced OHCA, 81% of arrests were witnessed, and pulseless electrical activity was the most common initial rhythm (40%). More than 72% of the patients had cardiac etiology for their arrests, and 55% underwent targeted temperature management. A total of 38% of patients survived to hospital discharge. There was no significant association between PaO2 at any time interval and neurological outcome at hospital discharge. Hyperoxemia at 12 hours after cardiac arrest was associated with decreased odds of survival (OR 0.17 [0.03-0.89], p = 0.032). There was no significant association between arterial oxygen tension measured within the first 48 hours after cardiac arrest and neurological outcome.

Therapeutic hypothermia and temperature management · cohort or longitudinal · 34 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 →

Visual Function, Social Position, and Health and Life Chances: The UK Biobank Study.

Importance: The adverse impact of visual impairment and blindness and correlations with socioeconomic position are known. Understanding of the effect of the substantially more common near-normal vision (mild impairment) and associations with social position as well as health and life chances is limited. Objective: To investigate the association of visual health (across the full acuity spectrum) with social determinants of general health and the association between visual health and health and social outcomes. Design, setting, and participants: A cross-sectional epidemiologic study was conducted using UK Biobank data from 6 regional centers in England and Wales. A total of 112 314 volunteers (aged 40-73 years) were assessed in June 2009 and July 2010. Data analysis was performed from May 20, 2013, to November 19, 2014. Main outcomes and measures: Habitual (correction if prescribed) distance visual acuity was used to assign participants to 1 of 8 categories from bilateral normal visual acuity (logMAR, 0.2 or better; Snellen equivalent, 6/9.5 or better) to visual impairment or blindness (logMAR, 0.5 or worse; Snellen equivalent, 6/19 or worse) using World Health Organization and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision taxonomy. Relationships between vision, key social determinants and health and social outcomes (including the main factors that define an individual's life-the social, economic, educational, and employment opportunities and outcomes experienced by individuals during their life course) were examined using multivariable regression. Results: Of the of 112 314 participants, 61 169 were female (54.5%); mean (SD) age was 56.8 (8.1) years. A total of 759 (0.7%) of the participants had visual impairment or blindness, and an additional 25 678 (22.9%) had reduced vision in 1 or both eyes. Key markers of social position were independently associated with vision in a gradient across acuity categories; in a gradient of increasing severity, all-cause impaired visual function was associated with adverse social outcomes and impaired general and mental health. These factors, including having no educational qualifications (risk ratio [RR], 1.86 [95% CI, 1.69-2.04]), having a higher deprivation score (RR, 1.08 [95% CI, 1.07-1.09]), and being in a minority ethnic group (eg, Asian) (RR, 2.05 [95% CI, 1.83-2.30]), were independently associated with being in the midrange vision category (at legal threshold for driving). This level of vision was associated with an increased risk of being unemployed (RR, 1.55 [95% CI, 1.31-1.84]), having a lower-status job (RR, 1.24 [95% CI, 1.09-1.41]), living alone (RR, 1.24 [95% CI, 1.10-1.39]), and having mental health problems (RR, 1.12 [95% CI, 1.04-1.20]). Conclusions and relevance: Impaired vision in adults is common, and even near-normal vision, potentially unrecognized without assessment, has a tangible influence on quality of life. Because inequalities in visual health by social position mirror other health domains, inclusion of vision in generic initiatives addressing health inequalities could address the existing significant burden of underrecognized and/or latent visual disability. Longitudinal investigations are needed to elucidate pathophysiologic pathways and target modifiable mechanisms.

JAMA ophthalmology · cohort or longitudinal · 132 citationsread the source →

Factors Driving Citizen Engagement With Government TikTok Accounts During the COVID-19 Pandemic: Model Development and Analysis.

Background: During the COVID-19 pandemic, growth in citizen engagement with social media platforms has enabled public health departments to accelerate and improve health information dissemination, developing transparency and trust between governments and citizens. In light of these benefits, it is imperative to learn the antecedents and underlying mechanisms for this to maintain and enhance engagement. Objective: The aim of this study is to determine the factors and influencing mechanisms related to citizen engagement with the TikTok account of the National Health Commission of China during the COVID-19 pandemic. Methods: Using a web crawler, 355 short videos were collected from the Healthy China account on TikTok (with more than 3 million followers throughout China), covering the period from January 21, 2020, to April 25, 2020. The title and video length, as well as the number of likes, shares, and comments were collected for each video. After classifying them using content analysis, a series of negative binomial regression analyses were completed. Results: Among the 355 videos, 154 (43.4%) related to guidance for clinicians, patients, and ordinary citizens, followed by information concerning the government's handling of the pandemic (n=100, 28.2%), the latest news about COVID-19 (n=61, 17.2%), and appreciation toward frontline emergency services (n=40, 11.3%). Video length, titles, dialogic loop, and content type all influenced the level of citizen engagement. Specifically, video length was negatively associated with the number of likes (incidence rate ratio [IRR]=0.19, P<.001) and comments (IRR=0.39, P<.001). Title length was positively related to the number of shares (IRR=24.25, P=.01), likes (IRR=8.50, P=.03), and comments (IRR=7.85, P=.02). Dialogic loop negatively predicted the number of shares (IRR=0.56, P=.03). In comparison to appreciative information, information about the government's handling of the situation (IRR=5.16, P<.001) and guidelines information (IRR=7.31, P<.001) were positively correlated with the number of shares, while the latest news was negatively related to the number of likes received (IRR=0.46, P=.004). More importantly, the relationship between predictors and citizen engagement was moderated by the emotional valence of video titles. Longer videos with positive titles received a higher number of likes (IRR=21.72, P=.04) and comments (IRR=10.14, P=.047). Furthermore, for short videos related to government handling of the pandemic (IRR=14.48, P=.04) and guidance for stakeholders (IRR=7.59, P=.04), positive titles received a greater number of shares. Videos related to the latest news (IRR=66.69, P=.04) received more likes if the video title displayed higher levels of positive emotion. Conclusions: During the COVID-19 pandemic, videos were frequently published on government social media platforms. Video length, title, dialogic loop, and content type significantly influenced the level of citizen engagement. These relationships were moderated by the emotional valence of the video's title. Our findings have implications for maintaining and enhancing citizen engagement via government social media.

Journal of medical Internet research · 46 citationsread the source →

Expression and genetic variability of PCDH11Y, a gene specific to Homo sapiens and candidate for susceptibility to psychiatric disorders.

Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive-compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically-matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders.

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · cohort or longitudinal · 38 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 →

Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype.

The insula and amygdala are implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non-dissociative (PTSD-DS) and dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity between individual insula subregions and the amygdala has not been investigated in persons with PTSD, with or without the dissociative subtype. We examined insula subregion (anterior, mid, and posterior) functional connectivity with the bilateral amygdala using a region-of-interest seed-based approach via PickAtlas and SPM8. Resting-state fMRI was conducted with (n=61) PTSD patients (n=44 PTSD-DS; n=17 PTSD+DS), and (n=40) age-matched healthy controls. When compared to controls, the PTSD-DS group displayed increased insula connectivity (bilateral anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in both hemispheres, and the PTSD+DS group displayed increased insula connectivity (bilateral anterior, left mid, and left posterior) to the left basolateral amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion connectivity (bilateral anterior, left mid, and right posterior) to the left basolateral amygdala was found in PTSD+DS. Depersonalization/derealization symptoms and PTSD symptom severity correlated with insula subregion connectivity to the basolateral amygdala within PTSD patients. This study is an important first step in elucidating patterns of neural connectivity associated with unique symptoms of arousal/interoception, emotional processing, and awareness of bodily states, in PTSD and its dissociative subtype.

Psychiatry research. Neuroimaging · 95 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. Neurobiol. 23, 294–303. (doi:10.1016/j.conb.2013.01.017) Crossref, PubMed, ISI, Google Scholar3Levy DJ, Glimcher PW. 2012The root of all value: a neural common currency for choice. Curr. Opin. Neurobiol. 22, 1027–1038. (doi:10.1016/j.conb.2012.06.001) Crossref, PubMed, ISI, Google Scholar4Kringelbach ML, Berridge KC. 2009Towards a functional neuroanatomy of pleasure and happiness. Trends Cogn. Sci. 13, 479–487. (doi:10.1016/j.tics.2009.08.006) Crossref, PubMed, ISI, Google Scholar5Brown S, Gao X, Tisdelle L, Eickhoff LM. 2011Naturalizing aesthetics: brain areas for aesthetic appraisal across sensory modalities. Neuroimage 58, 250–258. (doi:10.1016/j.neuroimage.2011.06.012) Crossref, PubMed, ISI, Google Scholar6Reybrouck M, Eerola T. 2017Music and its inductive power: a psychobiological and evolutionary approach to musical emotions. Front. Psychol. 8, 494. (doi:10.3389/fpsyg.2017.00494) Crossref, PubMed, ISI, Google Scholar7Blood AJ, Zatorre RJ. 2001Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc. Natl Acad. Sci. USA 98, 11 818–11 823. (doi:10.1073/pnas.191355898) Crossref, ISI, Google Scholar8Mallik A, Chandra ML, Levitin DJ. 2017Anhedonia to music and mu-opioids: evidence from the administration of naltrexone. Sci. Rep. 7, 41952. (doi:10.1038/srep41952) Crossref, PubMed, ISI, Google Scholar9Barrett LF. 2015How emotions are made: the secret life of the brain. London, UK: Macmillan. Google Scholar10Bloom P. 2010How pleasure works: the new science of why we like what we like. New York, NY: Norton. Google Scholar11Chatterjee A. 2014The aesthetic brain: how we evolved to desire beauty and enjoy art. New York, NY: Oxford University Press. Google Scholar12Spence C. 2017Gastrophysics: the new science of eating. London, UK: Penguin. Google Scholar13Leder H, Belke B, Oeberst A, Augustin D. 2004A model of aesthetic appreciation and aesthetic judgments. Br. J. Psychol. 95, 489–508. (doi:10.1348/0007126042369811) Crossref, PubMed, ISI, Google Scholar14Vessel EA, Rubin N. 2010Beauty and the beholder: highly individual taste for abstract, but not real-world images. J. Vis. 10, 1–14. (doi:10.1167/10.2.18) Crossref, PubMed, ISI, Google Scholar15Minissale G. 2013The psychology of contemporary art. Cambridge, UK: Cambridge University Press. Crossref, Google Scholar16Muth C, Pepperell R, Carbon C-C. 2013Give me Gestalt! Preference for cubist artworks revealing high detectability of objects. Leonardo 46, 488–489. (doi:10.1162/LEON_a_00649) Crossref, ISI, Google Scholar17Deacon TW. 1997The symbolic species: the co-evolution of language and the brain. New York, NY: Norton. Google Scholar18Henshilwood CS, d'Errico F. 2011Homo symbolicus: the dawn of language, imagination and spirituality. Amsterdam, The Netherlands: John Benjamins Publishing Co. Crossref, Google Scholar19Carroll N. 2008Aesthetic experience, art and artists. In Aesthetic experience (eds Shusterman R, Tomlin A), pp. 145–165. New York, NY: Routledge. Google Scholar20Kivy P. 2012What really happened in the eighteenth century: the 'Modern System' re-examined (again). Br. J. Aesthetics 52, 61–74. (doi:10.1093/aesthj/ayr046) Crossref, ISI, Google Scholar21Shiner L. 2001The invention of art: a cultural history. Chicago, IL: University of Chicago Press. Crossref, Google Scholar22Anderson RL. 1989Art in small-scale societies. 2nd edn. Englewood Cliffs, NJ: Prentice Hall. Google Scholar23Silvia PJ. 2009Looking past pleasure: anger, confusion, disgust, pride, surprise, and other unusual aesthetic emotions. Psychol. Aesthetics Creat. Arts 3, 48–51. (doi:10.1037/a0014632) Crossref, ISI, Google Scholar24Eco U. 2007On ugliness. London, UK: Harvill Secker. Google Scholar25Silvia PJ, Brown EM. 2007Anger, disgust, and the negative aesthetic emotions: expanding an appraisal model of aesthetic experience. Psychol. Aesthetics Creat. Arts 1, 100–106. (doi:10.1037/1931-3896.1.2.100) Crossref, Google Scholar26Huron D. 2006Sweet anticipation: music and the psychology of expectation. Cambridge, MA: MIT Press. Crossref, Google Scholar27Fitch W. 2006The biology and evolution of music: a comparative perspective. Cognition 100, 173–215. (doi:10.1016/j.cognition.2005.11.009) Crossref, PubMed, ISI, Google Scholar28Trainor LJ, Zatorre RJ. 2009The neurobiological basis of musical expectations. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 171–183. Oxford, UK: Oxford University Press. Google Scholar29Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ. 2011Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nat. Neurosci. 14, 257–262. (doi:10.1038/nn.2726) Crossref, PubMed, ISI, Google Scholar30Salimpoor VN, Zatorre RJ. 2013Neural interactions that give rise to musical pleasure. Psychol. Aesthetics Creat. Arts 7, 62–75. (doi:10.1037/a0031819) Crossref, ISI, Google Scholar31Whaley J, Sloboda J, Gabrielsson A. 2009Peak experiences in music. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 452–461. Oxford, UK: Oxford University Press. Google Scholar32Skov M, Nadal M.In press. Art is not special: an assault on the last lines of defense against the naturalization of the human mind. Rev. Neurosci. (doi:10.1515/revneuro-2017-0085) ISI, Google Scholar33Chatterjee A. 2011Neuroaesthetics: a coming of age story. J. Cogn. Neurosci. 23, 53–62. (doi:10.1162/jocn.2010.21457) Crossref, PubMed, ISI, Google Scholar34Pearce MT, Zaidel DW, Vartanian O, Skov M, Leder H, Chatterjee A, Nadal M. 2016Neuroaesthetics: the cognitive neuroscience of aesthetic experience. Perspect. Psychol. Sci. 11, 265–279. (doi:10.1177/1745691615621274) Crossref, PubMed, ISI, Google Scholar35Nadal M, Vartanian O, Skov M. 2017Psychological models of art reception must be empirically grounded. Behav. Brain Sci. 40, 36–37. (doi:10.1017/S0140525X17001790) Crossref, ISI, Google Scholar36Nadal M, Skov M. 2017Top–down and bottom–up: front to back: comment on 'Move me, astonish me… delight my eyes and brain: the Vienna integrated model of top–down and bottom–up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates' by Matthew Pelowski et al. Phys. Life Rev. 21, 148–149. (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 →

Psychological distress, depression, anxiety, and life satisfaction following COVID-19 infection: evidence from 11 UK longitudinal population studies.

Background: Evidence on associations between COVID-19 illness and mental health is mixed. We aimed to examine whether COVID-19 is associated with deterioration in mental health while considering pre-pandemic mental health, time since infection, subgroup differences, and confirmation of infection via self-reported test and serology data. Methods: We obtained data from 11 UK longitudinal studies with repeated measures of mental health (psychological distress, depression, anxiety, and life satisfaction; mental health scales were standardised within each study across time) and COVID-19 status between April, 2020, and April, 2021. We included participants with information available on at least one mental health outcome measure and self-reported COVID-19 status (suspected or test-confirmed) during the pandemic, and a subset with serology-confirmed COVID-19. Furthermore, only participants who had available data on a minimum set of covariates, including age, sex, and pre-pandemic mental health were included. We investigated associations between having ever had COVID-19 and mental health outcomes using generalised estimating equations. We examined whether associations varied by age, sex, ethnicity, education, and pre-pandemic mental health, whether the strength of the association varied according to time since infection, and whether associations differed between self-reported versus confirmed (by test or serology) infection. Findings: Between 21 Dec, 2021, and July 11, 2022, we analysed data from 54 442 participants (ranging from a minimum age of 16 years in one study to a maximum category of 90 years and older in another; including 33 200 [61·0%] women and 21 242 [39·0%] men) from 11 longitudinal UK studies. Of 40 819 participants with available ethnicity data, 36 802 (90·2%) were White. Pooled estimates of standardised differences in outcomes suggested associations between COVID-19 and subsequent psychological distress (0·10 [95% CI 0·06 to 0·13], I2=42·8%), depression (0·08 [0·05 to 0·10], I2=20·8%), anxiety (0·08 [0·05 to 0·10], I2=0·0%), and lower life satisfaction (-0·06 [-0·08 to -0·04], I2=29·2%). We found no evidence of interactions between COVID-19 and sex, education, ethnicity, or pre-pandemic mental health. Associations did not vary substantially between time since infection of less than 4 weeks, 4-12 weeks, and more than 12 weeks, and were present in all age groups, with some evidence of stronger effects in those aged 50 years and older. Participants who self-reported COVID-19 but had negative serology had worse mental health outcomes for all measures than those without COVID-19 based on serology and self-report. Participants who had positive serology but did not self-report COVID-19 did not show association with mental health outcomes. Interpretation: Self-reporting COVID-19 was longitudinally associated with deterioration in mental health and life satisfaction. Our findings emphasise the need for greater post-infection mental health service provision, given the substantial prevalence of COVID-19 in the UK and worldwide. Funding: UK Medical Research Council and UK National Institute for Health and Care Research.

The lancet. Psychiatry · 52 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 →

Psychological impacts from COVID-19 among university students: Risk factors across seven states in the United States.

Background: University students are increasingly recognized as a vulnerable population, suffering from higher levels of anxiety, depression, substance abuse, and disordered eating compared to the general population. Therefore, when the nature of their educational experience radically changes-such as sheltering in place during the COVID-19 pandemic-the burden on the mental health of this vulnerable population is amplified. The objectives of this study are to 1) identify the array of psychological impacts COVID-19 has on students, 2) develop profiles to characterize students' anticipated levels of psychological impact during the pandemic, and 3) evaluate potential sociodemographic, lifestyle-related, and awareness of people infected with COVID-19 risk factors that could make students more likely to experience these impacts. Methods: Cross-sectional data were collected through web-based questionnaires from seven U.S. universities. Representative and convenience sampling was used to invite students to complete the questionnaires in mid-March to early-May 2020, when most coronavirus-related sheltering in place orders were in effect. We received 2,534 completed responses, of which 61% were from women, 79% from non-Hispanic Whites, and 20% from graduate students. Results: Exploratory factor analysis on close-ended responses resulted in two latent constructs, which we used to identify profiles of students with latent profile analysis, including high (45% of sample), moderate (40%), and low (14%) levels of psychological impact. Bivariate associations showed students who were women, were non-Hispanic Asian, in fair/poor health, of below-average relative family income, or who knew someone infected with COVID-19 experienced higher levels of psychological impact. Students who were non-Hispanic White, above-average social class, spent at least two hours outside, or less than eight hours on electronic screens were likely to experience lower levels of psychological impact. Multivariate modeling (mixed-effects logistic regression) showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously. Conclusion: Inadequate efforts to recognize and address college students' mental health challenges, especially during a pandemic, could have long-term consequences on their health and education.

PloS one · 340 citationsread the source →

Religious Fasting of Muslim Patients After Metabolic and Bariatric Surgery: a Modified Delphi Consensus.

Background: Fasting during Ramadan is one of the five pillars of the Muslim faith. Despite the positive effects of fasting on health, there are no guidelines or clear recommendations regarding fasting after metabolic/bariatric surgery (MBS). The current study reports the result of a modified Delphi consensus among expert metabolic/bariatric surgeons with experience in managing patients who fast after MBS. Methods: A committee of 61 well-known metabolic and bariatric surgeons from 24 countries was created to participate in the Delphi consensus. The committee voted on 45 statements regarding recommendations and controversies around fasting after MBS. An agreement/disagreement ≥ of 70.0% was regarded as consensus. Results: The experts reached a consensus on 40 out of 45 statements after two rounds of voting. One hundred percent of the experts believed that fasting needs special nutritional support in patients who underwent MBS. The decision regarding fasting must be coordinated among the surgeon, the nutritionist and the patient. At any time after MBS, 96.7% advised stopping fasting in the presence of persistent symptoms of intolerance. Seventy percent of the experts recommended delaying fasting after MBS for 6 to 12 months after combined and malabsorptive procedures according to the patient's situation and surgeon's experience, and 90.1% felt that proton pump inhibitors should be continued in patients who start fasting less than 6 months after MBS. There was consensus that fasting may help in weight loss, improvement/remission of non-alcoholic fatty liver disease, dyslipidemia, hypertension and type 2 diabetes mellitus among 88.5%, 90.2%, 88.5%, 85.2% and 85.2% of experts, respectively. Conclusion: Experts voted and reached a consensus on 40 statements covering various aspects of fasting after MBS.

Obesity surgery · 11 citationsread the source →

A review of patients with advanced cervical cancer presenting to palliative care services at Queen Elizabeth Central Hospital in Blantyre, Malawi.

Background: Cervical cancer is the commonest cancer affecting women in Malawi, which has the highest rate of this disease in the world. Most cases are diagnosed at an advanced stage. Aim: To describe the symptom burden, palliative care interventions, and outcomes of cervical cancer patients who entered care at Tiyanjane Clinic in Blantyre, Malawi, between January and December 2012. Methods: We reviewed the case files of 72 patients presenting to our hospital-based palliative care service over one year. Results: The mean age was 49.5 years. Twenty-six patients (36%) were HIV-positive and the majority of these (n = 22; 85%) were on antiretroviral medication at presentation to palliative care. Pain (n = 66; 92%), vaginal discharge (n = 44; 61%), and unpleasant odour (n = 37; 51%) were commonly reported. Over a third of patients (n = 26; 36%) reported pain in two or more sites. Fourteen patients (19%) reported vaginal bleeding. Spousal breakdown (through widowhood or divorce) was noted in over half (n = 41; 57%) of all cases. Pain relief was provided to 69 (96%) of the patients (morphine to 40 patients; 56%). Common interventions provided included metronidazole tablets (used vaginally), sanitary items, and counselling. At the end of the study period, 18 patients (25%) were still under the care of palliative services. Conclusions: Access to medications such as morphine, metronidazole and tranexamic acid can improve quality of life, even when radiotherapy is limited. Health care teams require necessary skills and training, including how to perform a comprehensive assessment, with an emphasis on the provision of psychosexual counselling, to assist with the complexity of symptoms occurring in this vulnerable group.

Malawi medical journal : the journal of Medical Association of Malawi · 24 citationsread the source →

Factors associated with mental health outcomes in a Muslim community following the Christchurch terrorist attack.

Background: On 15 March 2019, a white supremacist terrorist attacked two mosques in Christchurch, New Zealand. Fifty-one people were killed and another 40 sustained non-fatal gunshot injuries. Aims: To examine the mental health of the Muslim community, and individual and exposure-related factors associated with mental health outcomes. Method: This is the baseline analysis of a longitudinal study of adults from the Muslim community interviewed 11-32 months after the shootings. It included a diagnostic interview (MINI), measures of sociodemographic factors, prior mental health, prior traumatic events, exposure in the attacks, discrimination, life stressors, social support and religious coping. Logistic regression models examined associations with mental health outcomes. Results: The sample comprised 189 participants (mean age 41 (s.d. = 13); 60% female), and included: bereaved, 17% (n = 32); injured survivors 12% (n = 22); non-injured survivors, 19% (n = 36); family members of survivors, 35% (n = 67); and community members without the above exposures, 39% (n = 74). Overall, 61% had at least one mental disorder since the attacks. Those bereaved (P < 0.01, odds ratio 4.28, 95% CI 1.75-10.49) and survivors, whether injured (P < 0.001, odds ratio 18.08, 95% CI 4.70-69.60) or not (P < 0.01, odds ratio 5.26, 95% CI 1.99-13.89), had greater odds of post-traumatic stress disorder. Those bereaved (P < 0.001, odds ratio 5.79, 95% CI 2.49-13.46) or injured (P = 0.04, odds ratio 4.43, 95% CI 1.07-18.28) had greater odds of depression. Conclusions: Despite unique features of this attack on a Muslim population, findings accord with previous studies. They suggest generalisability of psychopathology after terror attacks, and that being bereaved or directly experiencing such events is associated with adverse mental health outcomes. Trial registration number: The study is registered on the Australian NZ Clinical Trials Registry (ACTRN12620000909921).

BJPsych open · 3 citationsread the source →

Multidisciplinary clinic dedicated to treating youth with pediatric acute-onset neuropsychiatric syndrome: presenting characteristics of the first 47 consecutive patients.

Background: Abrupt, dramatic onset obsessive-compulsive disorder (OCD) and/or eating restriction with at least two coinciding symptoms (anxiety, mood dysregulation, irritability/aggression/oppositionality, behavioral regression, cognitive deterioration, sensory or motor abnormalities, or somatic symptoms) defines pediatric acute-onset neuropsychiatric syndrome (PANS). Descriptions of clinical data in such youth are limited. Methods: We reviewed charts of 53 consecutive patients evaluated in our PANS Clinic; 47 met PANS symptom criteria but not all met the requirement for "acute onset." Patients meeting full criteria for PANS were compared with patients who had a subacute/insidious onset of symptoms. Results: Nineteen of 47 (40%) patients in the study had acute onset of symptoms. In these patients, autoimmune/inflammatory diseases and psychiatric disorders were common in first-degree family members (71% and 78%, respectively). Most acute-onset patients had a relapsing/remitting course (84%), prominent sleep disturbances (84%), urinary issues (58%), sensory amplification (66%), gastrointestinal symptoms (42%), and generalized pain (68%). Inflammatory back pain (21%) and other arthritis conditions (28%) were also common. Suicidal and homicidal thoughts and gestures were common (44% and 17%, respectively) as were violent outbursts (61%). Group A streptococcus (GAS) was the most commonly identified infection at onset (21%) and during flares (74%). Rates of the above-mentioned characteristics did not differ between the acute-onset group and the subacute/insidious-onset groups. Low levels of immunoglobulins were more common in the subacute/insidious-onset group (75%) compared with the acute-onset group (22%), but this was not statistically significant (p=0.06). Conclusions: In our PANS clinic, 40% of patients had acute onset of symptoms. However, those with and without acute onset of symptoms had similar symptom presentation, rates of inflammatory conditions, somatic symptoms, and violent thoughts and behaviors. GAS infections were the most commonly identified infection at onset and at symptom flares. Because of the wide variety of medical and psychiatric symptoms, youth with PANS may require a multidisciplinary team for adequate care management.

Journal of child and adolescent psychopharmacology · 99 citationsread the source →

Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research.

Background: The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. Objectives: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. Methods: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. Results: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. Discussion: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. https://doi.org/10.1289/EHP5133.

Environmental health perspectives · 66 citationsread the source →

Frequency, intensity, and correlates of spiritual pain in advanced cancer patients assessed in a supportive/palliative care clinic.

Objective: Regular assessments of spiritual distress/spiritual pain among patients in a supportive/palliative care clinic (SCPC) are limited or unavailable. We modified the Edmonton Symptom Assessment Scale (ESAS) by adding spiritual pain (SP) to the scale (0 = best, 10 = worst) to determine the frequency, intensity, and correlates of self-reported SP (≥1/10) (pain deep in your soul/being that is not physical) among these advanced cancer patients. Method: We reviewed 292 consecutive consults of advanced cancer patients (ACPs) who were evaluated at our SCPC between October of 2012 and January of 2013. Symptoms were assessed using the new instrument (termed the ESAS-FS). Results: The median age of patients was 61 (range = 22-92). Some 53% were male; 189 (65%) were white, 45 (15%) African American, and 34 (12%) Hispanic. Some 123 of 282 (44%) of ACPs had SP (mean (95% CI) = 4(3.5-4.4). Advanced cancer patients with SP had worse pain [mean (95% CI) = 5.3(4.8, 5.8) vs. 4.5(4.0, 5.0)] (p = 0.02); depression [4.2(3.7, 4.7) vs. 2.1(1.7, 2.6), p < 0.0001]; anxiety [4.2(3.6, 4.7) vs. 2.5(2.0, 3.0), p < 0.0001]; drowsiness [4.2(3.7, 4.7) vs. 2.8(2.3, 3.2), p < 0.0001]; well-being [5.4(4.9, 5.8) vs. 4.5(4.1, 4.9), p = 0.0136]; and financial distress (FD) [4.4(3.9, 5.0) vs. 2.2(1.8, 2.7), p < 0.0001]. Spiritual pain correlated (Spearman) with depression (r = 0.45, p < 0.0001), anxiety (r = 0.34, p < 0.0001), drowsiness (r = 0.26, p < 0.0001), and FD (r = 0.44, p < 0.0001). Multivariate analysis showed an association with FD [OR (95% Wald CI) = 1.204(1.104-1.313), p < 0.0001] and depression [1.218(1.110-1.336), p < 0.0001]. The odds that patients who had SP at baseline would also have SP at follow-up were 182% higher (OR = 2.82) than for patients who were SP-negative at baseline (p = 0.0029). SP at follow-up correlated with depression (r = 0.35, p < 0.0001), anxiety (r = 0.25, p = 0.001), well-being (r = 0.27, p = 0.0006), nausea (r = 0.29, p = 0.0002), and financial distress (r = 0.42, p < 0.0001). Significance of results: Spiritual pain, which is correlated with physical and psychological distress, was reported in more than 40% of ACPs. Employment of the ESAS-FS allows ACPs with SP to be identified and evaluated in an SCPC. More research is needed.

Palliative & supportive care · 86 citationsread the source →

Prevalence and management of chronic insomnia in Swiss primary care: Cross-sectional data from the "Sentinella" practice-based research network.

We investigated the prevalence and treatment of patients with chronic insomnia presenting to Swiss primary care physicians (PCPs) part of "Sentinella", a nationwide practice-based research network. Each PCP consecutively asked 40 patients if they had sleep complaints, documented frequency, duration, comorbidities, and reported ongoing treatment. We analysed data of 63% (83/132) of the PCPs invited. The PCPs asked 76% (2,432/3,216) of included patients about their sleep (51% female); 31% (761/2,432) of these had had insomnia symptoms; 36% (875/2,432) had current insomnia symptoms; 11% (269/2,432) met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for chronic insomnia (61% female). In all, 75% (201/269) of patients with chronic insomnia had comorbidities, with 49% (99/201) reporting depression. Chronic insomnia was treated in 78% (209/269); 70% (188/268) took medication, 38% (102/268) benzodiazepines or benzodiazepine receptor agonists, 32% (86/268) took antidepressants. Only 1% (three of 268) had been treated with cognitive behavioural therapy for insomnia (CBT-I). A third of patients presenting for a non-urgent visit in Swiss primary care reported insomnia symptoms and 11% met the DSM-5 criteria for chronic insomnia. Hypnotics were the most common treatment, but almost no patients received first-line CBT-I. Reducing the burden of insomnia depends on disseminating knowledge about and access to CBT-I, and encouraging PCPs to discuss it with and offer it as a first-line treatment to patients with chronic insomnia.

Journal of sleep research · 30 citationsread the source →

Assisted reproductive technology treatment and risk of breast cancer: a population-based cohort study.

Study question: Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation? Summary answer: The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years. What is known already: The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment. Study design, size, duration: The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994-2016. Participants/materials, setting, methods: Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18-46 years). Results are presented as hazard ratios (HRs) with corresponding CIs. Main results and the role of chance: During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12-1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29-1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09-2.08). Limitations, reasons for caution: Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation. Wider implications of the findings: An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk. Study funding/competing interest(s): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest. Trial registration number: N/A.

Human reproduction (Oxford, England) · 7 citationsread the source →

Prevalence and severity of symptoms across the menopause transition: cross-sectional findings from the Australian Women's Midlife Years (AMY) Study.

Background: The premenopause-to-perimenopause transition is defined by the Stages of Reproductive Aging Workshop +10 (STRAW+10) criteria according to changed menstrual cycle frequency. However, this approach is unhelpful for women and gender-diverse people with oligomenorrhoea or amenorrhoea, and also because a range of diverse symptoms have been ascribed to menopause. We investigated the prevalence and severity of symptoms from the late reproductive stage to late postmenopause, identifying those which might best differentiate menopause onset. Methods: The Australian Women's Midlife Years (AMY) Study was a nationally representative cross-sectional study of women aged 40-69 years who were recruited via a non-probability panel using online and offline sources between Oct 27, 2023, and March 19, 2024. To be eligible, participants needed to be able to complete a questionnaire in English. Menopausal symptoms were assessed using the Menopause-specific Quality of Life (MENQOL) questionnaire. Symptom prevalence and severity over the previous 4 weeks was calculated with 95% CIs, with prevalence ratios adjusted for age, BMI, and other demographic variables. Findings: 8096 women were recruited: 5509 women were classified using STRAW+10 as premenopausal (n=1250), early perimenopausal (n=344), late perimenopausal (n=271), and postmenopausal (n=3644). Among moderately-to-severely bothersome symptoms, hot flushes showed the greatest change in prevalence from premenopause (8·8% [95% CI 7·2-10·4]) to late perimenopause (37·3% [31·5-43·0]; adjusted prevalence ratio 4·74 [95% CI 3·64-6·19]). Less variation was apparent for other symptoms, including poor memory and low mood. Vaginal dryness was the most discriminative sexual symptom from premenopause to late perimenopause (adjusted prevalence ratio 2·54 [95% CI 1·78-3·61]). Women with vasomotor symptoms and changed menstrual flow had more prevalent moderately-to-severely bothersome symptoms compared with women without vasomotor symptoms. Compared with premenopausal women with vasomotor symptoms and changed menstrual flow, early perimenopausal women with vasomotor symptoms reported a higher prevalence of poor memory (adjusted prevalence ratio 1·36 [95% CI 1·06-1·75]). Interpretation: Our findings suggest that moderately-to-severely bothersome vasomotor symptoms can reliably indicate the onset of perimenopause in women with oligomenorrhoea or amenorrhoea. Although other symptoms might be caused or exacerbated by menopause, other factors contributing to their occurrence need to be considered and included in management and care. Additionally, treatment options and care pathways are crucial to improve wellbeing during the perimenopause. Funding: National Health and Medical Research Council. Translations: For the Chinese and Spanish translations of the abstract see Supplementary Materials section.

The lancet. Diabetes & endocrinology · 9 citationsread the source →

Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia.

Background: A standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiography is recommended following community-acquired pneumonia; however, its utility in monitoring recovery from COVID-19 pneumonia remains unclear. Methods: This was a prospective single-centre observational cohort study. Patients hospitalised with severe COVID-19 pneumonia (admission duration ≥48 h and oxygen requirement ≥40% or critical care admission) underwent face-to-face assessment at 4-6 weeks post-discharge. The primary outcome was radiological resolution of COVID-19 pneumonitis (Radiographic Assessment of Lung Oedema score <5). Secondary outcomes included clinical outcomes, symptom questionnaires, mental health screening (Trauma Screening Questionnaire, seven-item Generalised Anxiety Disorder assessment and nine-item Patient Health Questionnaire) and physiological testing (4-m gait speed (4MGS) and 1-min Sit-to-Stand (STS) tests). Results: 119 patients were assessed between June 3, 2020 and July 2, 2020 at median (interquartile range (IQR)) 61 (51-67) days post-discharge: mean±sd age 58.7±14.4 years, median (IQR) body mass index 30.0 (25.9-35.2) kg·m-2, 62% male and 70% ethnic minority. Despite radiographic resolution of pulmonary infiltrates in 87%, modified Medical Research Council Dyspnoea (breathlessness) scale grades were above pre-COVID-19 baseline in 44%, and patients reported persistent fatigue (68%), sleep disturbance (57%) and breathlessness (32%). Screening thresholds were breached for post-traumatic stress disorder (25%), anxiety (22%) and depression (18%). 4MGS was slow (<0.8 m·s-1) in 38% and 35% desaturated by ≥4% during the STS test. Of 56 thoracic computed tomography scans performed, 75% demonstrated COVID-19-related interstitial and/or airways disease. Conclusions: Persistent symptoms, adverse mental health outcomes and physiological impairment are common 2 months after severe COVID-19 pneumonia. Follow-up chest radiography is a poor marker of recovery; therefore, holistic face-to-face assessment is recommended to facilitate early recognition and management of post-COVID-19 sequelae.

ERJ open research · 117 citationsread the source →

Women Oncologists' Perceptions and Factors Associated With Decisions to Pursue Academic vs Nonacademic Careers in Oncology.

Importance: Women outnumber men in US medical school enrollment, but they represent less than 40% of academic oncology faculty. Objective: To identify the key factors associated with female oncologists' decision to pursue academic or nonacademic oncology practice and to characterize their perceptions about their current career. Design, setting, and participants: This cross-sectional survey study was distributed through email and social media to female physicians in academic and nonacademic oncology practice in the United States. The survey was open for 3 months, from August 1 to October 31, 2020. Main outcomes and measures: No single primary study outcome was established because of the cross-sectional nature of the survey. Data were collected anonymously and analyzed using t tests for continuous variables and χ2 tests for categorical variables. Results: Among the 667 female respondents, 422 (63.2%) identified as academic oncologists and 245 (36.8%) identified as nonacademic oncologists. Approximately 25% of respondents reported that their spouse or partner (156 [23.5%]) and/or family (176 [26.4%]) extremely or moderately affected their decision to pursue academic practice. Academic oncologists perceived the biggest sacrifice of pursuing academics to be time with loved ones (181 [42.9%]). Nonacademic oncologists perceived the biggest sacrifice of pursuing academics to be pressure for academic promotion (102 [41.6%]). Respondents had different perceptions of how their gender affected their ability to obtain a chosen job, with 116 academic oncologists (27.6%) and 101 nonacademic oncologists (41.2%) reporting a positive or somewhat positive impact (P = .001). More than half of the women surveyed (54.6% academic oncologists [230]; 50.6% nonacademic oncologists [123]; P = .61) believed they were less likely to be promoted compared with male colleagues. Academic and nonacademic oncologists reported rarely or never having a sense of belonging in their work environment (33 [7.9%] and 5 [2.0%]; P < .001). Most respondents reported that they would choose the same career path again (301 academic oncologists [71.3%]; 168 nonacademic oncologists [68.6%]); however, 92 academic oncologists (21.9%) reported they were likely to pursue a career outside of academic oncology in the next 5 years. Conclusions and relevance: This survey study found that a spouse or partner and/or family were factors in the career choice of both academic and nonacademic oncologists and that female gender was largely perceived to adversely affect job promotion. Given that more than 20% of female academic oncologists were considering leaving academia, gender inequality is at high risk of continuing if the culture is not addressed.

JAMA network open · 32 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 →

Insomnia before and after treatment for anxiety and depression.

Background: Insomnia increases the likelihood of developing a mood or anxiety disorder. Moreover, symptoms of anxiety and depression, such as worry and rumination, contribute to insomnia. Given these relationships, there is a need to delineate how these disorders respond to treatment when they are comorbid. Methods: 266 individuals presenting for anxiety and/or depression symptoms participated in this study in which symptoms of insomnia, anxiety, depression, disability, and sleep length were assessed. 102 of these patients were treated with internet-based cognitive behavioral therapy (iCBT) for anxiety and/or depression and 61 completed the treatment. Pre- to post-treatment symptom changes were examined in this subset. Results: Insomnia, as measured by the Insomnia Severity Index, was evident in 40% of the patients. Individuals with insomnia reported more severe symptoms of anxiety and depression than individuals without insomnia. iCBT focused on anxiety and/or depression was associated with reductions in symptoms of insomnia, anxiety, depression, and disability. Total sleep time did not change over treatment. Limitations: As the data were collected in routine care, there was no control group and no longer term follow-up assessment. Conclusions: These findings highlight the importance of insomnia across anxiety and depressive disorders. They further demonstrate that treatment for anxiety and/or depression appears to improve comorbid insomnia symptoms, though may be ineffective in changing sleep duration.

Journal of affective disorders · 81 citationsread the source →

A longitudinal analysis of loneliness among older people in Great Britain.

Longitudinal studies of loneliness among older people are comparatively rare. At 8 years after the initial survey in 1999-2000, we followed up on the 999 people aged 65+ years who were living in the community in the United Kingdom. We found that 583 participants were still alive, and 287 (58%) participated in the follow-up survey. The overall prevalence of loneliness at both time points was very similar, with 9% reporting severe loneliness; 30% reporting that they were sometimes lonely, and 61% reporting that they were never lonely. We developed a 12-category typology to describe changes in loneliness across the follow-up period and report that 60% of participants had a stable loneliness rating, with 40-50% rating themselves as never lonely, and 20-25% rating themselves as persistently lonely; 25% demonstrated decreased loneliness, and approximately 15% demonstrated worse loneliness. Changes in loneliness were linked with changes in marital status, living arrangements, social networks, and physical health. Importantly improvements in physical health and improved social relationships were linked to reduced levels of loneliness. This result suggests that strategies to combat loneliness are not confined to the arena of social interventions such as befriending services, which aim to build and support social embeddedness, but may also result from the treatment of chronic and long-term health conditions.

The Journal of psychology · 166 citationsread the source →

The Support, Education, and Research in Chronic Heart Failure Study (SEARCH): a mindfulness-based psychoeducational intervention improves depression and clinical symptoms in patients with chronic heart failure.

Background: The Support, Education, and Research in Chronic Heart Failure (SEARCH) study was designed to assess the impact of a mindfulness-based psychoeducational intervention on clinical outcomes, depression, and quality of life in patients with chronic heart failure (CHF). Although research has shown that psychosocial factors including depression are important risk factors for adverse events in patients with CHF, no large clinical trials have investigated the efficacy of psychosocial interventions to reduce these factors in this population. Methods: This was a prospective cohort study of 208 adults with left ventricular ejection fraction < or =40% and CHF geographically assigned to treatment or control groups with follow-up at 3, 6, and 12 months. Treatment groups met weekly for 8 consecutive weeks for training in mindfulness meditation, coping skills, and support group discussion. Results: Subjects had a mean age of 61 years, left ventricular ejection fraction 26%, and median New York Heart Association class II. The majority were treated with angiotensin-converting enzyme inhibitors (80%) and beta-blockers (86%). At baseline, patients in the treatment group had more severe CHF with higher New York Heart Association class (P = .0209) and more severe psychological distress (Center of Epidemiology - Depression, Profile of Mood States; P < .05). When compared with controls, treatment resulted in lower anxiety (Profile of Mood States, P = .003), depression (Center of Epidemiology - Depression, P = .05), improved symptoms (Kansas City Cardiomyopathy Questionnaire symptom scale, P = .033) and clinical scores (Kansas City Cardiomyopathy Questionnaire clinical score, P = .024) over time. There were no treatment effects on death/rehospitalization at 1 year. Conclusions: An 8-week mindfulness-based psychoeducational intervention reduced anxiety and depression; this effect was attenuated at 1 year. Importantly, the intervention led to significantly better symptoms of CHF at 12 months compared to control subjects. Our results suggest that interventions of this type might have a role in optimal therapy for CHF.

American heart journal · 96 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 →