Interactions of the GABRG2 polymorphisms and childhood trauma on suicide attempt and related traits in depressed patients

Yin, Honglei; Galfalvy, Hanga; Zhang, Bin; Tang, Weiwei; Xin, Qianqian; Li, Enze; Xue, Xiang; Li, Qiyang; Ye, Junping; Yan, Na; Mann, J. John

doi:10.1016/j.jad.2020.01.126

Cited by 11 publications

(9 citation statements)

References 51 publications

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“…Suicide victims had decreased GABA-A α1 receptor subunit expression in the frontal cortex [89]. Later studies have shown polymorphisms of the γ-2 subunit in suicide attempts, suggesting that the longest variant of the GABA-A receptor γ-2 subunit is associated with protection against suicide attempts [90]. In both suicidal adults and adolescents, decreased expression of GABA-A receptors on platelets was also found [91].…”

Section: Glutaminergic and Gabaergic Neurotransmissionmentioning

confidence: 98%

Neurobiological Basis of Increased Risk for Suicidal Behaviour

Wisłowska-Stanek

Kołosowska

Maciejak

2021

Cells

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According to the World Health Organization (WHO), more than 700,000 people die per year due to suicide. Suicide risk factors include a previous suicide attempt and psychiatric disorders. The highest mortality rate in suicide worldwide is due to depression. Current evidence suggests that suicide etiopathogenesis is associated with neuroinflammation that activates the kynurenine pathway and causes subsequent serotonin depletion and stimulation of glutamate neurotransmission. These changes are accompanied by decreased BDNF (brain-derived neurotrophic factor) levels in the brain, which is often linked to impaired neuroplasticity and cognitive deficits. Most suicidal patients have a hyperactive hypothalamus–pituitary–adrenal (HPA) axis. Epigenetic mechanisms control the above-mentioned neurobiological changes associated with suicidal behaviour. Suicide risk could be attenuated by appropriate psychological treatment, electroconvulsive treatment, and drugs: lithium, ketamine, esketamine, clozapine. In this review, we present the etiopathogenesis of suicide behaviour and explore the mechanisms of action of anti-suicidal treatments, pinpointing similarities among them.

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Section: Glutaminergic and Gabaergic Neurotransmissionmentioning

confidence: 98%

Neurobiological Basis of Increased Risk for Suicidal Behaviour

Wisłowska-Stanek

Kołosowska

Maciejak

2021

Cells

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“…Genotyping rs211034 (5:162102714) was found to be related with suicidal behavior in our previous research (23). It was located in intron, and 40bp downstream of the alternatively spliced exon of the GABRG2 gene.…”

Section: Severity Of Depressionmentioning

confidence: 91%

“…In our previous studies, we found low expression of a GABRG2 (GABA A receptor subunit gamma2) isoform which has an alternatively spliced exon in suicide brain ( 1 ), then we found that allele A of rs211034, which was located in an intron near the alternatively spliced exon of the GABRG2 gene, was protective for suicide attempt (SA) ( 23 ), these results suggested GABRG2 as a potential genetic factor in suicide, and rs211034 as a potential site in the risk of suicide. Thus, we hypothesized that this specific genetic variation (rs211034) may interact with reported CT to influence cognition related to suicide or depression risk.…”

Section: Introductionmentioning

confidence: 99%

Influence of the GABA Receptor Subunit Gene Polymorphism and Childhood Sexual Abuse on Processing Speed in Major Depression and Suicide Attempt

et al. 2021

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Background: Suicide is moderately heritable and also more common in those who report childhood abuse. Previously, it was found that allele A of GABRG2 (GABA A receptor subunit gamma2) polymorphism rs211034 was protective in a suicide attempt (SA). Hence, it was proposed that rs211034 may interact with childhood trauma to influence cognitive deficits related to SA or depression risk. Genetic variants may predict the benefits of certain cognitive treatments.Methods: A total of 52 individuals who had attempted suicide, 59 individuals with major depressive disorder (MDD) or bipolar depression who had not previously attempted suicide, and 90 healthy volunteers were subjected to the modified Suicide Stroop task and were clinically assessed using the Childhood Trauma Questionnaire (CTQ) and Hamilton Depression Scale-24 items (HAMD-24). rs211034 was genotyped using Sanger sequencing.Results: After correcting for covariates, depressed participants displayed longer reaction times for all emotional conditions, including suicide-related words, compared with healthy controls. Depressed suicide attempters displayed longer reaction times for negative words than depressed non-attempters. Depressed non-attempters displayed higher interference scores for negative words compared with healthy controls. There was an interaction between rs211034 risk allele and the effects of reported childhood sexual abuse (CSA) on reaction time for all emotional words and suicide-related words. Carriers of the rs211034 risk allele A exhibited shorter reaction times, but the protective effects of this allele were eliminated in those exposed to reported CSA.Conclusion: Only limited results were found regarding effects of a past suicide attempt on response times to emotional and suicide-related words, but there was an overall effect of major depression on slower response time. Protective genetic effects of the rs211034 A allele on this slowing were eliminated in those with a history of sexual abuse during childhood. Further research is needed to better characterize the mechanisms underlying the effects of childhood trauma on these genetic effects.

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“…Physiological genes encoding neuropeptides, such as hormones, enzymes, and receptors are considered. Previously investigated genes have been found to overlap between aggressive behaviours and many psychiatric disorders, such as PTSD [ 15 , 26 , 27 ]. Physiological candidate genes investigated in the past are now GWAS hits for traits related to aggression and anxiety disorders.…”

Section: Introductionmentioning

confidence: 99%

Physiological Genomics Plays a Crucial Role in Response to Stressful Life Events, the Development of Aggressive Behaviours, and Post-Traumatic Stress Disorder (PTSD)

Magwai

Xulu

2022

Genes

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Physiological genomics plays a crucial role in responding to stressful life events, such as violence and traumatic stress. This exposure to traumatic stress can trigger several physiological pathways, which are associated with genetic variability. Exposure to traumatic stress can result in the development of behavioural and psychiatric disorders, such as aggressive behaviour and anxiety disorders. Several genes play a crucial role in the neurophysiological response to chronic stress and trauma. These essential genes include monoamine oxidase A (MAOA), solute carrier family 6 member 4 (SLC6A4), brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), dopamine receptor 2 and 4 (DRD2 and DRD4), and FK506 binding protein 5 (FKBP5). Genetic variations in several genes have been found to have altered physiological response, which associates with the development of several behavioural traits. Interestingly, previous studies show that there is an interplay between aggressive behaviour and anxiety disorders, which may be associated with physiological genomics structure. The physiological responses are based on genetic architecture and its molecular reaction. Understanding physiological genomics may show underpinnings related to the development of aggressive behaviours and their interaction with anxiety disorders. This review aims to discuss the association between different physiological genes and the development of psychiatric disorders related to aggressive behaviours and anxiety disorders, such as post-traumatic stress disorder.

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Interactions of the GABRG2 polymorphisms and childhood trauma on suicide attempt and related traits in depressed patients

Cited by 11 publications

References 51 publications

Neurobiological Basis of Increased Risk for Suicidal Behaviour

Neurobiological Basis of Increased Risk for Suicidal Behaviour

Influence of the GABA Receptor Subunit Gene Polymorphism and Childhood Sexual Abuse on Processing Speed in Major Depression and Suicide Attempt

Physiological Genomics Plays a Crucial Role in Response to Stressful Life Events, the Development of Aggressive Behaviours, and Post-Traumatic Stress Disorder (PTSD)

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