Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior

Abstract

Suicidal behavior, which ranks among the top 10 causes of death worldwide, is an important public-health problem and a psychiatric disorder, which has been the subject of considerable study. Studies have shown association between the serotonin transporter (5-HTT) gene and suicidal behavior, although a proportion of alternative studies have produced contrary results both in terms of positive and negative findings, possibly reflecting inadequate statistical power and the use of different populations. Using the cumulative data from recent years in both European and, more particularly, Asian populations, this updated meta-analysis seeks to examine whether the aggregate data provide evidence of statistical significance, and to clarify the contradictory findings suggested by previous studies. It covers all published studies using multiple research methods up to January 2006. Compared with a previous meta-analysis, which found no association between the 5-HTTLPR polymorphism and suicidal behavior (P = 0.38), the current results (39 studies) suggest a significant association with a P-value of 0.0068 (overall odds ratio = 0.88 (0.8,0.97)), and supports the involvement of the brain 5-HTT in the pathogenesis of suicidal behavior.

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

“…This interpretation is in line with numerous reports of suicide being associated with S-allele of the serotonin transporter (5-HTT) promoter polymorphism. [43][44][45] The presence of this allele seems to reduce transcription efficiency for the 5-HTT gene leading to decreased 5-HTT expression and, consequently, decreased serotonin uptake and increased levels of serotonin. 46 The above suggestion, however, contradicts a more prominent hypothesis which regards the pathophysiology of suicide and depression as a deficiency in serotonergic neurotransmission caused by decreased levels of brain serotonin.…”

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.…”

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

“…As low central nervous system serotonin (5-HT) turnover is related to SB (Mann, 2003), serotonin-related genes have been the focus of several association studies (Courtet et al, 2005). Meta-analyses have confirmed the association of SB with variants in the serotonin transporter gene (5-HTT, or SLC6A4) (Li and He, 2007) and the tryptophan hydroxylase 1 gene (TPH1) (Bellivier et al, 2004). The genes encoding brain-derived neurotrophic factor (BDNF) and its receptor, the neurotrophic tyrosine kinase receptor type 2 (NTRK2) are also promising candidates as they are involved in the regulation and growth of 5-HT neurons .…”