Hypothalamic-pituitary-adrenal axis dysfunction as a neurobiological correlate of emotion dysregulation in adolescent suicide

Braquehais, María Dolores; Picouto, María Dolores; Casas, Miquel; Sher, Leo

doi:10.1007/s12519-012-0358-0

Cited by 42 publications

(34 citation statements)

References 85 publications

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“…This could be due to alteration in the interaction between hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic (5-HTergic) systems following chronic stress. The dysfunction of both systems may partly explain the neurobiology of emotional dysfunction in animals that have been exposed to stress [68]. …”

Section: Discussionmentioning

confidence: 99%

Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress

Al-Rahbi

Zakaria

Othman

et al. 2013

BioMed Research International

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This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups, (n = 10 per group). These were non-stressed sham-operated control rats, stressed sham-operated control rats, non-stressed OVX rats, and stressed OVX rats. The rats were subjected to social instability stress procedure for 15 days. Novel object recognition, open field, and forced swim tests were conducted after the stress procedure. Serum estradiol, ACTH and corticosterone levels were measured using commercially available ELISA kits. Lower serum estradiol level and uterine weight with higher weight gain were observed in OVX rats compared to sham-operated controls. Serum ACTH, and corticosterone levels were higher in stressed compared to non-stressed groups. Memory deficit and anxiety- and depressive-like behaviour were significantly increased in stressed compared to non-stressed OVX rats but these changes were not seen in sham-operated controls. These results suggest that the high circulating corticosterone acts synergistically with low circulating estradiol to exert negative effects on mood and memory function.

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Section: Discussionmentioning

confidence: 99%

Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress

Al-Rahbi

Zakaria

Othman

et al. 2013

BioMed Research International

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“…Major depressive disorder (MDD) [1][2][3][4][5] and suicidal behavior [6][7][8][9][10] are associated with hypothalamic-pituitary adrenal (HPA) axis overactivity and with excessive cortisol response to stress. One cause of excessive cortisol release is impaired glucocorticoid receptor (GR) feedback inhibition.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid Receptor-Related Genes: Genotype and Brain Gene Expression Relationships to Suicide and Major Depressive Disorder

et al. 2016

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Introduction We tested the relationship between genotype, gene expression and suicidal behavior and MDD in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior and major depressive disorder (MDD); FK506 binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2) and Glucocorticoid Receptor (NR3C1). Materials and Methods Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N=277) and a postmortem sample (N=209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9) (N=59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). Results We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, that was associated with increased risk of suicide attempt (OR=1.58, t=6.03, p=0.014). Six SNPs on this gene, three SNPs on SKA2 and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex. One NR3C1 transcript had lower expression in suicide relative to non-suicide sudden death cases (b=-0.48, SE=0.12, t=-4.02, adjusted p=0.004). Conclusion We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the prefrontal cortex. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior.

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“…Dysregulation of HPA axis activity is separably implicated in the pathology of addiction disorders (see reviews by Sinha, 2008; Picciotto et al, 2010; Picetti et al, 2013) and depression (see reviews by Braquehais et al, 2012; Laryea et al, 2012; Lopresti et al, 2013). Modification of HPA axis signaling can alter drug seeking behavior (Deroche-Gamonet et al, 2003; Pastor et al, 2008; Wang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL/6J mice during abstinence from chronic ethanol consumption

Pang

Catchlove

et al. 2013

fphar

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Depression is a commonly reported co-morbidity during rehabilitation from alcohol use disorders and its presence is associated with an increased likelihood of relapse. Interventions which impede the development of depression could be of potential benefit if incorporated into treatment programs. We previously demonstrated an ameliorative effect of physical exercise on depressive behaviors in a mouse model of alcohol abstinence. Here, we show that environmental enrichment (cognitive and social stimulation) has a similar beneficial effect. The hypothalamic-pituitary-adrenal (HPA) axis is a key physiological system regulating stress responses and its dysregulation has been separably implicated in the pathophysiology of depression and addiction disorders. We performed a series of dexamethasone challenges and found that mice undergoing 2 weeks of alcohol abstinence had significantly greater corticosterone and ACTH levels following a DEX-CRH challenge compared to water controls. Environmental enrichment during alcohol abstinence corrected the abnormal DEX-CRH corticosterone response despite a further elevation of ACTH levels. Examination of gene expression revealed abstinence-associated alterations in glucocorticoid receptor (Gr), corticotrophin releasing hormone (Crh) and pro-opiomelanocortin (Pomc1) mRNA levels which were differentially modulated by environmental enrichment. Overall, our study demonstrates a benefit of environmental enrichment on alcohol abstinence-associated depressive behaviors and HPA axis dysregulation.

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Hypothalamic-pituitary-adrenal axis dysfunction as a neurobiological correlate of emotion dysregulation in adolescent suicide

Abstract: Correlating HPA axis dysfunction with psychological factors such as ED could lead to a better understanding of the role of HPA abnormalities in adolescent suicide and may enhance preventive and treatment strategies.

Cited by 42 publications

References 85 publications

Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress

Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress

Glucocorticoid Receptor-Related Genes: Genotype and Brain Gene Expression Relationships to Suicide and Major Depressive Disorder

Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL/6J mice during abstinence from chronic ethanol consumption

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