Genetics of suicide

Abstract

The concept that genetic factors contribute to the complex trait of suicidal behaviour has stimulated much work aimed at identifying susceptibility genes. So far molecular genetic studies focused on the serotonergic pathway as the intent to die and the lethality of suicide acts were related to the serotonergic system. Two genes have so far emerged as being involved in the vulnerability for suicidality: first, the intronic polymorphisms (A218C or A779C) of the tryptophan hydroxylase 1 (TPH1) gene, which was suggested as a quantitative risk factor for suicidal behaviour; second, the insertion/deletion polymorphism of the serotonin transporter gene (5-HTTLPR), which does not seem to be involved in general suicidal behaviour, but in violent and repeated suicide attempts. The data have further shown that the MAOA gene, which is consistently associated with impulsive-aggressive personality traits, is not related to suicide but might induce violent methods in subjects with other suicide risk factors. Predominantly negative were the findings with any type of the serotonin receptors and inconsistent with catecholamine-synthesizing and -metabolizing enzymes or with the dopaminergic receptors. This paper reviews the status of current knowledge in this area, points to the weakness of the investigations and presents new approaches beyond the serotonergic system.

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

“…8,154 On the other hand, there appears to be some degree of specificity as no G Â E was identified for generalised anxiety disorder or anxiety symptoms. 15,34 While 5-HTTLPR genotype is not reliably directly associated with depression, 151 the more severe and multiple adverse outcomes including violent suicide, 155,156 suicide attempts among alcohol-dependent subjects 157 and comorbid alcohol dependence with depression 158,159 are directly associated with 5-HTTLPR s allele loading. Although a meta-analysis reported a weak association between 5-HTTLPR s allele and alcoholism per se, 158 this association was driven by samples with comorbid mental health problems.…”

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

“…Beyond this, the side effects of tryptophan depletion in humans also need to be assessed as this essential amino acid is the precursor for the neurotransmitter serotonin. In humans, depleted serotonin levels can lead to psychological disturbances and increased risk of suicide (114), which could negate any life extension effect of tryptophan restriction.…”

Serotonergic modulation of suicidal behaviour: integrating preclinical data with clinical practice and psychotherapy

“…the short (s) allele of the 5-HttLPR is associated with reduced serotonin transporter (5-Htt) protein availability and function (Canli and Lesch, 2007) compared with the long (L) form. the presence of at least one s allele has been proposed as a predictor of suicidal behaviour (Bondy et al 2006). Considering the different suicidal phenotypes, including a review of related meta-analyses, the s allele seems to be associated with impulsive and aggressive suicidal behaviours and completed suicide (Bondy et al 2000) and violent (Bayle et al 2003;Bellivier et al 2000;Courtet et al 2001) as well as repeated suicide attempts (Courtet et al 2004).…”