Elsevier

Biological Psychiatry

Volume 55, Issue 10, 15 May 2004, Pages 1023-1030
Biological Psychiatry

Original article
Association between serotonin transporter gene promoter polymorphism and suicide: results of a meta-analysis

https://doi.org/10.1016/j.biopsych.2004.02.006Get rights and content

Abstract

Background

There is strong evidence supporting a role for serotonin system dysfunction in the pathology of suicidal behavior. Many studies have examined the association between a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR) and suicide but have yielded inconsistent results. Our goal here, by analyzing the cumulative data from primary literature, was to determine conclusively whether there is an association.

Methods

Three meta-analyses were performed. One compared the 5-HTTLPR polymorphism between suicidal subjects and normal control subjects; another compared suicide attempters with nonattempters of the same psychiatric diagnoses; the last one compared either violent or nonviolent suicidal subjects with normal control subjects.

Results

We found no association between 5-HTTLPR polymorphism and suicidal behavior (p = .379). When we compared subjects with the same psychiatric diagnoses, the genotypes carrying the s allele were significantly more frequent in suicide attempters than in nonattempters (p = .004). In addition, the s allele was associated with violent suicide (p = .0001) but not with nonviolent suicide (p = 1.00).

Conclusions

Our results provide significant evidence supporting the association of the s allele of 5-HTTLPR polymorphism with suicidal behavior in the psychiatric population, also with violent suicide. These support a role for decreased serotonin transporter function in the vulnerability to suicide in a select population.

Section snippets

Literature search

To identify studies eligible for this meta-analysis, we conducted a computerized search (MEDLINE) using the following key words: “(serotonin transporter gene OR serotonin transporter OR 5-HTT)” AND “(suicide OR suicidal behavior).” We also used reference lists from identified articles and reviews to find additional articles not indexed by MEDLINE. In-press articles in psychiatric journals were also examined.

Inclusion criteria

Only those studies examining the 5-HTTLPR polymorphism were included in the current

Results

Through the literature search and selection based on the inclusion criteria, 25 studies were found (Baca-Garcia et al., 2002, Bayle et al., 2003, Bellivier et al., 2000, Bondy et al., 2000, Campi-Azevedo et al., 2003, Chong et al., 2000, Courtet et al., 2001, Courtet et al., 2003, Du et al., 1999, Du et al., 2001, Faludi et al., 2000, Fitch et al., 2001, Geijer et al., 2000, Gorwood et al., 2000, Ho et al., 2000, Hranilovic et al., 2003, Joiner et al., 2002, Mann et al., 2000, Ohara et al., 1998

Discussion

Suicide is a common comorbidity with psychiatric diseases. During past decades, despite much progress in the treatment of most of the common psychiatric diseases, there has been relatively little change in suicide rates. This reflects a paucity of understanding of the neurobiological bases of this complex behavioral trait. In this study, through analyzing its association with the 5-HTTLPR polymorphism by meta-analytic methods, we attempted to understand the contribution of a genetically altered

Acknowledgements

GT is supported partly by National Institute of Mental Health grants P50 MH60450 and R01 MH51290, and grants from the International Rett Syndrome Foundation, the National Alliance for Research on Schizophrenia and Depression, and the Stanley Foundation. P-YL is supported by Chang Gung Memorial Hospital, Taiwan.

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