Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology.

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OBJECTIVES. We aimed at reviewing studies exploring dysfunctional cognitive processes, and their neuroanatomical basis, in suicidal behaviour, and to develop a neurocognitive working model. Methods. A literature search was conducted. RESULTS. Several limitations were found. The main reported neuropsychological findings are a higher attention to specific negative emotional stimuli, impaired decision-making, lower problem-solving abilities, reduced verbal fluency, and possible reduced non-specific attention and reversal learning in suicide attempters. Neuroimaging studies mainly showed the involvement of ventrolateral orbital, dorsomedial and dorsolateral prefrontal cortices, the anterior cingulate gyrus, and, to a lesser extent, the amygdala. In addition, alterations in white matter connections are suggested. CONCLUSIONS. These studies support the concept of alterations in suicidal behaviour distinct from those of comorbid disorders. We propose that a series of neurocognitive dysfunctions, some with trait-like characteristics, may facilitate the development of a suicidal crisis during stressful circumstances: (1) an altered modulation of value attribution, (2) an inadequate regulation of emotional and cognitive responses, and (3) a facilitation of acts in an emotional context. This preliminary model may represent a framework for the design of future studies on the pathophysiology, prediction and prevention of these complex human behaviours.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations.

Suicidal behavior in older adults (65 years old and over) is a major public health issue in many countries. Suicide rates increase during the life course and are as high as 48.7/100,000 among older white men in the USA. Specific health conditions and stress factors increase the complexity of the explanatory model for suicide in older adults. A PubMed literature search was performed to identify most recent and representative studies on suicide risk factors in older adults. The aim of our narrative review was to provide a critical evaluation of recent findings concerning specific risk factors for suicidal thoughts and behaviors among older people: psychiatric and neurocognitive disorders, social exclusion, bereavement, cognitive impairment, decision making and cognitive inhibition, physical illnesses, and physical and psychological pain. We also aimed to approach the problem of euthanasia or physician-assisted suicide in older adults. Our main findings emphasize the need to integrate specific stress factors, such as feelings of social disconnectedness, neurocognitive impairment or decision making, as well as chronic physical illnesses and disability in suicide models and in suicide prevention programs in older adults. Furthermore, the chronic care model should be adapted for the treatment of older people with long-term conditions in order to improve the treatment of depressive disorders and the prevention of suicidal thoughts and acts.

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J Clin Psychiatry 2020;81(3):20com13370 To cite: Courtet P, Olié E, Debien C, et al. Keep socially (but not physically) connected and carry on: preventing suicide in the age of COVID-19.

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