The hormonal stress response and its measurement.
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301 to 325 of 897Emerging insights into hypothalamic-pituitary-gonadal axis regulation and interaction with stress signalling.
Reproduction and fertility are regulated via hormones of the hypothalamic-pituitary-gonadal (HPG) axis. Control of this reproductive axis occurs at all levels, including the brain and pituitary, and allows for the promotion or inhibition of gonadal sex steroid secretion and function. In addition to guiding proper gonadal development and function, gonadal sex steroids also act in negative- and positive-feedback loops to regulate reproductive circuitry in the brain, including kisspeptin neurones, thereby modulating overall HPG axis status. Additional regulation is also provided by sex steroids made within the brain, including neuroprogestins. Furthermore, because reproduction and survival need to be coordinated and balanced, the HPG axis is able to modulate (and be modulated by) stress hormone signalling, including cortiscosterone, from the hypothalamic-pituitary-adrenal (HPA) axis. This r…
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Farzi A, Fröhlich EE, Holzer P (2018)reviewMEDLINE-indexed journal, not yet read by usNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics337 citations Gut Microbiota and the Neuroendocrine System.
The microbial ecosystem that inhabits the gastrointestinal tract of all mammals-the gut microbiota-has been in a symbiotic relationship with its hosts over many millennia. Thanks to modern technology, the myriad of functions that are controlled or modulated by the gut microbiota are beginning to unfold. One of the systems that is emerging to closely interact with the gut microbiota is the body's major neuroendocrine system that controls various body processes in response to stress, the hypothalamic-pituitary-adrenal (HPA) axis. This interaction is of pivotal importance; as various disorders of the microbiota-gut-brain axis are associated with dysregulation of the HPA axis. The present contribution describes the bidirectional communication between the gut microbiota and the HPA axis and delineates the potential underlying mechanisms. In this regard, it is important to note that the commun…
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Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.
Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males,…
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Biomarkers of Suicide Attempt Behavior: Towards a Biological Model of Risk.
Purpose of review: The rising suicide rate in the USA will not be reversed without improved risk assessment and prevention practices. To date, the best method for clinicians to assess a patient's risk for suicide is screening for past suicide attempts in the patient and their family. However, neuroimaging, genomic, and biochemical studies have generated a body of findings that allow description of an initial heuristic biological model for suicidal behavior that may have predictive value.
Recent findings: We review studies from the past 3 years examining potential biological predictors of suicide attempt behavior. We divide findings into two major categories: (1) structural and functional brain imaging findings and (2) biochemical and genomic findings encompassing several systems, including major neurotransmitters (serotonin, catecholamines, GABA, and glutamate), the hypothalamic pituitar…
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The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities.
Over the past decade, our understanding of the role of stress in serious mental illness has become more sophisticated. In this paper, we revisit the neural diathesis-stress model of schizophrenia that was initially proposed in 1997 and updated in 2008. In light of cumulative research findings, we must now encompass evidence on the premorbid periods of psychosis, and our more nuanced understanding of hypothalamic-pituitary-adrenal (HPA) axis function and its association with neurodevelopmental, epigenetic, neurotransmitter, and inflammatory processes, as well as brain structure and function. Giving consideration to the methodological complexities that have become more apparent as research in this area has burgeoned, the various indices of HPA axis function, and the different stages of illness, we review relevant research published since the 2008 update of the model. We conclude by proposi…
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Neurobiological Interactions Between Stress and the Endocannabinoid System.
Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes. A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response. In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling have with respect to many of the effects of stress. Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels. Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a downregulation or loss of cannabinoid type 1 (CB1) receptors. With respect …
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Gordon JL, Girdler SS, Meltzer-Brody SE, Stika CS, Thurston RC, Clark CT, Prairie BA, Moses-Kolko E, Joffe H, Wisner KL (2015)reviewMEDLINE-indexed journal, not yet read by usThe American journal of psychiatry184 citations Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in perimenopausal depression: a novel heuristic model.
Objective: In this conceptual review, the authors propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition ("perimenopausal depression") involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation.
Method: The relevant literature in perimenopausal depression, including prevalence, predictors, and treatment with estrogen therapy, was reviewed. Subsequently, the growing evidence from animal models and clinical research in other reproductive mood disorders was synthesized to describe a heuristic model of perimenopausal depression development.
Results: The rate of major depressive disorder and clinically meaningful elevations in depressive symptoms increases two- to threefold during the menopause transition. While the mechanisms by which ovarian hormone fluctuation might impact mood are poorly understood, growi…
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Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.
Purpose: Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation.
Methods: Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress.
Findings: Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, envi…
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GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response.
Regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioural changes associated with early-life adversity. W…
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One is the deadliest number: the detrimental effects of social isolation on cerebrovascular diseases and cognition.
The deleterious effects of chronic social isolation (SI) have been recognized for several decades. Isolation is a major source of psychosocial stress and is associated with an increased prevalence of vascular and neurological diseases. In addition, isolation exacerbates morbidity and mortality following acute injuries such as stroke or myocardial infarction. In contrast, affiliative social interactions can improve organismal function and health. The molecular mechanisms underlying these effects are unknown. Recently, results from large epidemiological trials and pre-clinical studies have revealed several potential mediators of the detrimental effects of isolation. At least three major biological systems have been implicated: the neuroendocrine (HPA) axis, the immune system, and the autonomic nervous system. This review summarizes studies examining the relationship between isolation and m…
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Sex differences in the HPA axis.
The hypothalamic-pituitary-adrenal (HPA) axis is a major component of the systems that respond to stress, by coordinating the neuroendocrine and autonomic responses. Tightly controlled regulation of HPA responses is critical for maintaining mental and physical health, as hyper- and hypo-activity have been linked to disease states. A long history of research has revealed sex differences in numerous components of the HPA stress system and its responses, which may partially form the basis for sex disparities in disease development. Despite this, many studies use male subjects exclusively, while fewer reports involve females or provide direct sex comparisons. The purpose of this article is to present sex comparisons in the functional and molecular aspects of the HPA axis, through various phases of activity, including basal, acute stress, and chronic stress conditions. The HPA axis in females…
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Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?
Rationale: A robust epidemiological literature suggests an association between chronic stress and the development of affective disorders. However, the precise biological underpinnings of this relationship remain elusive. Central to the human response and adaptation to stress, activation and inhibition of the hypothalamic pituitary adrenal (HPA) axis involves a multi-level, multi-system, neurobiological stress response which is as comprehensive in its complexity as it is precarious. Dysregulation in this complex system has implications for human stress related illness.
Objectives: The pioneering research of Robert Purdy and colleagues has laid the groundwork for advancing our understanding of HPA axis regulation by stress-derived steroid hormones and their neuroactive metabolites (termed neurosteroids), which are potent allosteric modulators of GABAA receptor function in the central nervo…
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Jacobson L (2014)reviewMEDLINE-indexed journal, not yet read by usComprehensive Physiology95 citations Hypothalamic-pituitary-adrenocortical axis: neuropsychiatric aspects.
Evidence of aberrant hypothalamic-pituitary-adrenocortical (HPA) activity in many psychiatric disorders, although not universal, has sparked long-standing interest in HPA hormones as biomarkers of disease or treatment response. HPA activity may be chronically elevated in melancholic depression, panic disorder, obsessive-compulsive disorder, and schizophrenia. The HPA axis may be more reactive to stress in social anxiety disorder and autism spectrum disorders. In contrast, HPA activity is more likely to be low in PTSD and atypical depression. Antidepressants are widely considered to inhibit HPA activity, although inhibition is not unanimously reported in the literature. There is evidence, also uneven, that the mood stabilizers lithium and carbamazepine have the potential to augment HPA measures, while benzodiazepines, atypical antipsychotics, and to some extent, typical antipsychotics hav…
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Stress in adolescence and drugs of abuse in rodent models: role of dopamine, CRF, and HPA axis.
Rationale: Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction-related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse.
Objectives: Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic-pituitary-adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms.
Results and conclusions: Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influ…
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Stress and the reproductive axis.
There exists a reciprocal relationship between the hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes, wherein the activation of one affects the function of the other and vice versa. For example, both testosterone and oestrogen modulate the response of the HPA axis, whereas activation of the stress axis, especially activation that is repeating or chronic, has an inhibitory effect upon oestrogen and testosterone secretion. Alterations in maternal care can produce significant effects on both HPG and HPA physiology, as well as behaviour in the offspring at adulthood. For example, changes in reproductive behaviour induced by altered maternal care may alter the expression of sex hormone receptors such as oestrogen receptor (ER)α that govern sexual behaviour, and may be particularly important in determining the sexual strategies utilised by females. Stress i…
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Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems.
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is accepted as one of the fundamental biological mechanisms that underlie major depression. This hyperactivity is caused by diminished feedback inhibition of glucocorticoid (GC)-induced reduction of HPA axis signaling and increased corticotrophin-releasing hormone (CRH) secretion from the hypothalamic paraventricular nucleus (PVN) and extra-hypothalamic neurons. During chronic stress-induced inhibition of systemic feedback, cytosolic glucocorticoid receptor (GR) levels were significantly changed in the prefrontal cortex (PFC) and hippocampus, both structures known to be deeply involved in the pathogenesis of depression. Cytokines secreted by both immune and non-immune cells can markedly affect neurotransmission within regulatory brain circuits related to the expression of emotions; cytokines may also induce hormonal changes s…
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A review of lifestyle factors that contribute to important pathways associated with major depression: diet, sleep and exercise.
Research on major depression has confirmed that it is caused by an array of biopsychosocial and lifestyle factors. Diet, exercise and sleep are three such influences that play a significant mediating role in the development, progression and treatment of this condition. This review summarises animal- and human-based studies on the relationship between these three lifestyle factors and major depressive disorder, and their influence on dysregulated pathways associated with depression: namely neurotransmitter processes, immuno-inflammatory pathways, hypothalamic-pituitary-adrenal (HPA) axis disturbances, oxidative stress and antioxidant defence systems, neuroprogression, and mitochondrial disturbances. Increased attention in future clinical studies on the influence of diet, sleep and exercise on major depressive disorder and investigations of their effect on physiological processes will help…
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The link between child abuse and psychopathology: a review of neurobiological and genetic research.
Childhood abuse is associated with later psychopathology, including conduct disorder, antisocial personality disorder, anxiety and depression as well as a heightened risk of health and social problems. However, the neurobiological mechanisms by which childhood adversity increases vulnerability to psychopathology remain poorly understood. There is likely to be a complex interaction between environmental experiences (such as abuse) and individual differences in risk versus protective genes, which influences the neurobiological circuitry underpinning psychological and emotional development. Neuroendocrine studies indicate an association between early adversity and atypical development of the hypothalamic-pituitary-adrenal (HPA) axis stress response, which may predispose to psychiatric vulnerability in adulthood. Brain imaging research in children and adults is providing evidence of several …
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Sensitivity to the depressogenic effect of stress and HPA-axis reactivity in adolescence: a review of gender differences.
Adolescence is characterized by major biological, psychological, and social challenges, as well as by an increase in depression rates. This review focuses on the association between stressful experiences and depression in adolescence, and the possible role of the hypothalamus-pituitary-adrenal cortex (HPA-)axis in this link. Adolescent girls have a higher probability to develop depressive symptoms than adolescent boys and preadolescents. Increasing evidence indicates that girls' higher risk of depression is partly brought about by an increased sensitivity for stressful life events, particularly interpersonal stressors, which are highly prevalent in adolescent girls. Genetic risk factors for depression, as well as those for stress sensitivity, are often expressed differently in girls and boys. Also environmental adversity tends to affect girls' stress responses more than those of boys. Th…
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Investigations of HPA function and the enduring consequences of stressors in adolescence in animal models.
Developmental differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and ongoing development of glucocorticoid-sensitive brain regions in adolescence suggest that similar to the neonatal period of ontogeny, adolescence may also be a sensitive period for programming effects of stressors on the central nervous system. Although research on this period of life is scarce compared to early life and adulthood, the available research indicates that effects of stress exposure during adolescence differ from, and may be longer-lasting than, effects of the same stress exposure in adulthood. Research progress in animal models in this field is reviewed including HPA function and the enduring effects of stress exposures in adolescence on sensitivity to drugs of abuse, learning and memory, and emotional behaviour in adulthood. The effects of adolescent stress depend on a nu…
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Finn DP (2010)reviewMEDLINE-indexed journal, not yet read by usImmunobiology58 citations Endocannabinoid-mediated modulation of stress responses: physiological and pathophysiological significance.
The stress response is associated with a broad spectrum of physiological and behavioural effects including hypothalamo-pituitary-adrenal (HPA) axis activation, altered central nervous system activity, neuroimmune alterations, anxiety- and depressive-like behaviour and analgesia. While the acute stress response has essential survival value, chronic stress and dysfunction of the stress response can be maladaptive, contributing to the development and severity of psychiatric and pain disorders. The endogenous cannabinoid (endocannabinoid) system has emerged as an important lipid signalling system playing a key role in mediating and/or modulating behavioural, neurochemical, neuroendocrine, neuroimmune and molecular responses to stress. The weight of evidence, reviewed here, points largely to a system which serves to constrain HPA axis activity, facilitate adaptation or habituation of HPA axis…
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Research review: the neurobiology and genetics of maltreatment and adversity.
The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in turn sets the stage for a child's psychological and emotional development. This review provides a concise synopsis of those studies investigating the neurobiological and genetic factors associated with childhood maltreatment and adversity. We first provide an overview of the neuroendocrine findings, drawing from animal and human studies. These studies indicate an association between early adversity and atypical development of the hypothalamic-pituitary-adrenal (HPA) axis stress response, which can predispose to psychiatric vulnerability in adultho…
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Romeo RD (2010)reviewMEDLINE-indexed journal, not yet read by usFrontiers in neuroendocrinology179 citations Pubertal maturation and programming of hypothalamic-pituitary-adrenal reactivity.
Modifications in neuroendocrine function are a hallmark of pubertal development. These changes have many short- and long-term implications for the physiological and neurobehavioral function of an individual. The purpose of the present review is to discuss our current understanding of how pubertal development and stress interact to affect the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis that controls the hormonal stress response. A growing body of literature indicates that puberty is marked by dramatic transitions in stress reactivity. Moreover, recent studies indicate that exposure to stressors during pubertal maturation may result in enduring changes in HPA responsiveness in adulthood. As puberty is marked by a substantial increase in many stress-related psychological and physiological disorders (e.g., depression, anxiety, drug abuse), it is essential to unde…
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Ross A, Thomas S (2010)reviewMEDLINE-indexed journal, not yet read by usJournal of alternative and complementary medicine (New York, N.Y.)386 citations The health benefits of yoga and exercise: a review of comparison studies.
Objectives: Exercise is considered an acceptable method for improving and maintaining physical and emotional health. A growing body of evidence supports the belief that yoga benefits physical and mental health via down-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). The purpose of this article is to provide a scholarly review of the literature regarding research studies comparing the effects of yoga and exercise on a variety of health outcomes and health conditions.
Methods: Using PubMed((R)) and the key word "yoga," a comprehensive search of the research literature from core scientific and nursing journals yielded 81 studies that met inclusion criteria. These studies subsequently were classified as uncontrolled (n = 30), wait list controlled (n = 16), or comparison (n = 35). The most common comparison intervention (n = 10) involved e…
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Inflammation as a psychophysiological biomarker in chronic psychosocial stress.
The measurement of inflammation by biomarkers not only documents clinically relevant infections but also offers an important tool to pin point potentially harmful effects of chronic psychosocial stressors. This article focuses firstly on basic biology of inflammation and lists main biomarkers currently used in psycho-physiologic research. In the second part, the effects of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system as pathways modulating stress-related inflammation are discussed. Furthermore, current evidence of how chronic psychosocial stressors are related to alterations in inflammatory activity is presented. In summary, job stress, low socioeconomic status, childhood adversities as well as life events, caregiver stress, and loneliness were all shown to exert effects on immunologic activity.
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