Dataset Information

Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior.

ABSTRACT: Studies looking at the relationship of the hypothalamic-pituitary-adrenal (HPA) axis 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 (?=-0.47, 95% CI (-0.83, -0.11), p=0.01) compared with offspring with suicide-related behavior (SRB) but never attempted, non-suicidal offspring, and a healthy control group. The result remained significant even after controlling for sex, age, race, ethnicity, site, socio-economic status, and hour of the day when the TSST was conducted. Suicide attempters also showed lower baseline cortisol before the TSST (?=-0.45, 95% CI (-0.74, -0.17), p=0.002). However, there were no significant differences between the groups on cortisol reactivity to stress (?=4.5, 95% CI (-12.9, 22), p=0.61). Although subjects with suicide attempt and SRB have similar clinical and psychosocial characteristics, this is the first study to differentiate them biologically on HPA axis indices. Blunted HPA axis activity may increase risk for suicide attempt among individuals with psychopathology by reducing their ability to respond adaptively to ongoing stressors. These results may help better identify subjects at high risk for suicidal behavior for targeted prevention and intervention efforts.

SUBMITTER: Melhem NM

PROVIDER: S-EPMC4832012 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior.

Melhem Nadine M NM Keilp John G JG Porta Giovanna G Oquendo Maria A MA Burke Ainsley A Stanley Barbara B Cooper Thomas B TB Mann J John JJ Brent David A DA

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20151009 6

Studies looking at the relationship of the hypothalamic-pituitary-adrenal (HPA) axis 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 ...[more]

PMID: 26450815

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Project description:Little is known about the bio-behavioral mechanisms underlying and differentiating suicide attempts from non-suicidal self-injury (NSSI) in adolescents. Adolescents who attempt suicide or engage in NSSI often report significant interpersonal and social difficulties. Emotional face recognition ability is a fundamental skill required for successful social interactions, and deficits in this ability may provide insight into the unique brain-behavior interactions underlying suicide attempts versus NSSI in adolescents. Therefore, we examined emotional face recognition ability among three mutually exclusive groups: (1) inpatient adolescents who attempted suicide (SA, n = 30); (2) inpatient adolescents engaged in NSSI (NSSI, n = 30); and (3) typically developing controls (TDC, n = 30) without psychiatric illness. Participants included adolescents aged 13-17 years, matched on age, gender and full-scale IQ. Emotional face recognition was evaluated using the diagnostic assessment of nonverbal accuracy (DANVA-2). Compared to TDC youth, adolescents with NSSI made more errors on child fearful and adult sad face recognition while controlling for psychopathology and medication status (ps < 0.05). No differences were found on emotional face recognition between NSSI and SA groups. Secondary analyses showed that compared to inpatients without major depression, those with major depression made fewer errors on adult sad face recognition even when controlling for group status (p < 0.05). Further, compared to inpatients without generalized anxiety, those with generalized anxiety made fewer recognition errors on adult happy faces even when controlling for group status (p < 0.05). Adolescent inpatients engaged in NSSI showed greater deficits in emotional face recognition than TDC, but not inpatient adolescents who attempted suicide. Further results suggest the importance of psychopathology in emotional face recognition. Replication of these preliminary results and examination of the role of context-dependent emotional processing are needed moving forward.

Project description:Incidence of post-traumatic stress disorder (PTSD) ranges from 3 to 30% in individuals exposed to traumatic events, with the highest prevalence in groups exposed to combat, torture, or rape. To date, only a few FDA approved drugs are available to treat PTSD, which only offer symptomatic relief and variable efficacy. There is, therefore, an urgent need to explore new concepts regarding the biological responses causing PTSD. Animal models are an appropriate platform for conducting such studies. Herein, we examined the chronic behavioral and neurobiological effects of repeated unpredictable stress (RUS) in a mouse model. 12 weeks-old C57BL/6J male mice were exposed to a 21-day RUS paradigm consisting of exposures to a predator odor (TMT) whilst under restraint, unstable social housing, inescapable footshocks and social isolation. Validity of the model was assessed by comprehensive examination of behavioral outcomes at an acute timepoint, 3 and 6 months post-RUS; and molecular profiling was also conducted on brain and plasma samples at the acute and 6 months timepoints. Stressed mice demonstrated recall of traumatic memories, passive stress coping behavior, acute anxiety, and weight gain deficits when compared to control mice. Immunoblotting of amygdala lysates showed a dysregulation in the p75NTR/ProBDNF, and glutamatergic signaling in stressed mice at the acute timepoint. At 6 months after RUS, stressed mice had lower plasma corticosterone, reduced hippocampal CA1 volume and reduced brain-derived neurotrophic factor levels. In addition, glucocorticoid regulatory protein FKBP5 was downregulated in the hypothalamus of stressed mice at the same timepoint, together implicating an impaired hypothalamus-pituitary-adrenal-axis. Our model demonstrates chronic behavioral and neurobiological outcomes consistent with those reported in human PTSD cases and thus presents a platform through which to understand the neurobiology of stress and explore new therapeutic interventions.

Dataset Information

Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior.

Publications

Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior.

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