The Involvement of Hypothalamus–Pituitary–Adrenal (HPA) Axis in Suicide Risk (original) (raw)
Related papers
European Archives of Psychiatry and Clinical Neuroscience, 2010
Suicidal behavior and mood disorders are one of the world’s largest public health problems. The biological vulnerability for these problems includes genetic factors involved in the regulation of the serotonergic system and stress system. The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates the body’s response to stress and has complex interactions with brain serotonergic, noradrenergic and dopaminergic systems. Corticotropin-releasing hormone and vasopressin act synergistically to stimulate the secretion of ACTH that stimulates the biosynthesis of corticosteroids such as cortisol from cholesterol. Cortisol is a major stress hormone and has effects on many tissues, including on mineralocorticoid receptors and glucocorticoid receptors in the brain. Glucocorticoids produce behavioral changes, and one important target of glucocorticoids is the hypothalamus, which is a major controlling center of the HPA axis. Stress plays a major role in the various pathophysiological processes associated with mood disorders and suicidal behavior. Serotonergic dysfunction is a well-established substrate for mood disorders and suicidal behavior. Corticosteroids may play an important role in the relationship between stress, mood changes and perhaps suicidal behavior by interacting with 5-HT1A receptors. Abnormalities in the HPA axis in response to increased levels of stress are found to be associated with a dysregulation in the serotonergic system, both in subjects with mood disorders and those who engage in suicidal behavior. HPA over-activity may be a good predictor of mood disorders and perhaps suicidal behavior via abnormalities in the serotonergic system.
Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression
Biological Psychiatry, 2005
One of the most demanding tasks in psychiatry is to protect patients from suicidal attempts. Preventive strategies could be improved by increasing our knowledge on the pathophysiologic disturbances underlying this behavior. More than 70 -80% of suicides occur in the context of depressive disorders, in which dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most prominent neurobiological findings. So far data on the involvement of the HPA axis in the pathophysiology of suicidal behavior in depressed patients are controversial. Methods: In this retrospective study, we administered the combined dexamethasone-suppression/CRH stimulation (Dex/CRH) test to 310 patients with a depressive syndrome characterized at admission for acute and past suicidal behavior within the first 10 days after hospitalization. Results: Suicidal behavior in depressed patients, including past and recent suicide attempts as well as suicidal ideation, was associated with a lower adrenocorticotropin and cortisol response in the combined Dex/CRH test, with lowest hormone levels observed in patients with a recent suicide attempt. Discussion: The findings suggest that suicidal behavior may alter HPA axis regulation in depressed patients. Large-scale prospective studies assessing neuroendocrine changes may help to develop predictors for an early identification of patients at risk for committing suicide.
Hypothalamic-Pituitary-Adrenal Axis and Suicide
Annals of the New York Academy of Sciences, 1986
Adrenal steroid hormones are essential to human life and play a central role in maintaining survival in times of stress.' Indices of hypothalamic-pituitary-adrenal (HPA) axis function have been extensively evaluated in various psychiatric disturbances. There are at least three reasons for studying adrenal function in pathological emotional states:
Blunted HPA Axis Activity in Suicide Attempters Compared to those at High-Risk for Suicidal Behavior
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015
Studies looking at the relationship of the hypothalamic-pituitary-adrenal axis (HPA) to suicidal behavior and its risk factors, such as depression, childhood abuse, and impulsive aggression, report inconsistent results. These studies also do not always differentiate between subjects who go on to attempt suicide, suicidal subjects who never attempted suicide, and non-suicidal subjects with psychiatric disorders. In this study, we examined cortisol responses to an experimental stressor, the Trier Social Stress Test (TSST), in 208 offspring of parents with mood disorder. Offspring suicide attempters showed lower total cortisol output [β=-0.47, 95% CI (-0.83, -0.11), p=0.01] compared to offspring with suicide-related behavior but never attempted, non-suicidal offspring, and a healthy control group. The result remained significant even after controlling for sex, age, race, ethnicity, site, socioeconomic status, and hour of the day when the TSST was conducted. Suicide attempters also show...
Cortisol and suicidal behavior: A meta-analysis
Suicide is a major cause of death worldwide, responsible for 1.5% of all mortality. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. This meta-analytic review aimed (i) to estimate the strength and variability of the association between naturally fluctuating cortisol levels and suicidal behavior and (ii) to identify moderators of this relationship. A systematic literature search identified 27 studies (N = 2226; 779 suicide attempters and 1447 non-attempters) that met the study eligibility criteria from a total of 417 unique records initially examined. Estimates of effect sizes (r) obtained from these studies were analysed using Comprehensive Meta-Analysis. In these analyses, we compared participants identified as having a past history of suicide attempt(s) to those with no such history. Study quality, mean age of sample and percentage of male participants were examined as potential moderators. Overall, there was no significant effect of suicide group on cortisol. However, significant associations between cortisol and suicide attempts were observed as a function of age. In studies where the mean age of the sample was below 40 years the association was positive (i.e., higher cortisol was associated with suicide attempts; r = .234, p < .001), and where the mean age was 40 or above the association was negative (i.e., lower cortisol was associated with suicide attempts; r = −.129, p < .001). These findings confirm that HPA axis activity, as indicated by age-dependent variations in cortisol levels, is associated with suicidal behavior. The challenge for theory and clinical practice is to explain the complete reversal of the association with age and to identify its clinical implications.
Journal of Psychiatry …, 2010
BackgroundSuicidal behaviour aggregates in families, and the hypothalamic–pituitary–adrenal (HPA) axis and noradrenergic dysregulation may play a role in suicide risk. It is unclear whether stress dysregulation is a heritable trait of suicide or how it might increase risk. We investigated stress reactivity of the autonomic nervous system and the HPA axis in suicide predisposition and characterized the effect of this dysregulation on neuropsychologic function.MethodsIn this family-based study of first-degree relatives (n = 14) of suicide completers and matched controls with no family or personal history of suicidal behaviour (n = 14), participants underwent the Trier Social Stress Test (TSST). We used salivary α-amylase and cortisol levels to characterize stress reactivity and diurnal variation. We administered a series of neuropsychologic and executive function tests before and after the TSST.ResultsDespite normal diurnal variation, relatives of suicide completers exhibited blunted cortisol and α-amylase TSST reactivity. Although there were no baseline differences in conceptual reasoning, sustained attention or executive function, the relatives of suicide completers did not improve on measures of inhibition upon repeated testing after TSST. Secondary analyses suggested that these effects were related to suicide vulnerability independent of major depression.LimitationsThe sample size was small, and the design prevents us from disentangling our findings from the possible traumatic consequences of losing a relative by suicide.ConclusionsBlunted stress response may be a trait of suicide risk, and impairment of stress-induced executive function may contribute to suicide vulnerability.
Recent biologic studies on suicide
Suicide & life-threatening behavior, 1994
This paper selectively reviews the author's recent studies on suicidal behavior in depression. Data are reviewed from a study of depressed patients who had monoamine metabolites measured in both the cerebrospinal fluid (CSF) and urine. Depressed patients who had attempted suicide had significantly reduced CSF concentrations of the dopamine metabolite homovanillic acid (HVA) and significantly lower urinary outputs of HVA than patients who had not attempted suicide. Similarly, patients who went on to reattempt suicide over a 5-year follow-up period had both significantly reduced CSF concentrations of HVA and lower urinary outputs of HVA than patients who did not reattempt. These data suggest a role for diminished central dopaminergic neurotransmission in suicidal behavior in depression. Patients who had made a violent suicide attempt also showed evidence of dysregulation of the hypothalamic-pituitary-adrenal axis.
Salivary cortisol and suicidal behavior - A follow
2000
Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a common finding in Major Depressive Disorder. Similar studies on suicide attempters are less abundant, and the results are divergent. The main aim of the present study was to investigate HPA-axis parameters by the time of a suicide attempt and at follow-up in search for associations between HPA axis function and suicidal behavior.
Dialogues in clinical neuroscience, 2002
Disturbances in the serotonin (5-hydroxytryptamine, 5-HT) system constitute the neurobiological abnormality most consistently associated with suicide. This abnormality could be a marker of vulnerability predisposing individuals to auto-aggressive and impulsive behavior. However, other abnormalities, such as hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, have also been described in suicide victims. While inhibitory effects of adrenocorticosteroids on 5-HT(1A) receptor function have been shown in animals, HPA axis hyperactivity does not seem to be responsible for the reduced 5-HT activity found in depressed patients with a history of suicidal behavior. On the other hand, hypothalamic-pituitarythyroid (HPT) axis dysfunction, frequently observed in depression, may represent a compensatory response to reduced central 5-HT neurotransmission. Moreover, in depressed patients with a history of suicidal behavior, the absence of a functional link between HPT and dopamine activ...