1. ¹Laboratório de Farmacogenética, ICB, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil
2. ²Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil
3. ³Departamento de Morfologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil
4. ⁴Grupo de Pesquisa em Neuropsiquiatria Clínica e Molecular, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil

Correspondence: Professor H Correa, Departamento de Morfologia–ICB, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 312280-901 Belo Horizonte-MG, Brazil. E-mail: correa@task.com.br

SIR – The potential role of the functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) in suicidal behavior has been a matter of controversy. Since suicidal behavior is a complex, multideterminated phenomenon, we hypothesized that the conflicting results may be explained by differences in characterization of suicide attempts. Thus, a detailed phenotypic characterization of the suicide attempt is of major interest given that a biological factor could play a major role in some categories of suicidal behavior (eg violent or impulsive or more lethal or repetitive ones) but not in every one. We have previously found an association between lower serotonergic function and suicidal behavior in major depressed¹ and schizophrenic patients.² Thus, to test this hypothesis we investigated the 5-HTTLPR polymorphism in a well-characterized sample of in-patients, subgrouped according to lifetime suicide behavior characteristics and in a sample of healthy controls.

Patients with consecutive admissions, diagnosed according to the DSM-IV criteria based on a structured interview,³ with recurrent major depression (n=106) or schizophrenia (n=131) were enrolled. Healthy controls, without history of suicide, (n=75, staff or faculty members) were interviewed and were free of psychiatric illness, with no familial history of axis I psychiatric disorder up to first-degree relatives.

Suicide history was assessed using a semistructured interview^1,2 and a review of medical records. At least one close relative member was interviewed. This is important because a significant degree of past suicidal behavior may not be recorded during routine clinical assessment.⁴ Furthermore, we evaluated, for the most lethal lifetime suicide attempt; the lethality, using the Lethality Rating Scale (LRS), scored 0–8,^1,2 with a score of 3 or greater as a cutoff point; the intention with the Suicide Intent Scale (SIS);⁵ and the methods, classified as nonviolent (drug overdose) or violent (cutting beyond a superficial scratch, jumping from a height, shooting, hanging).

Differences in genotype were calculated by ² test. Difference between groups was tested with Student's t-test. Odds ratio with 95% confidence intervals was calculated using Wolf's method. Tests were two-tailed and results significant when P0.05.

Genotyping was performed as previously reported.⁶ There was no significant difference among healthy controls, schizophrenic and depressed patients in genotypic frequencies (²=0.544, d.f.=4, P=0.969) or in demographic parameters (sex, age, race). They were not in Hardy-Weinberg equilibrium (controls, ²=12.6; d.f.=2; P=0.002; schizophrenic patients; ²=8.64; d.f.=2, P=0.013 and depressed patients, ²=7.31, d.f.=2, P=0.026).

We grouped S-carriers together (LS+SS genotypes) in view of the fact that the S-allele acts in a nearly dominant way.⁷ S-carriers (n=123) exhibited no significant difference when compared to LL-carriers (n=114) concerning diagnosis, demographic (age, sex distribution, race) or sociocultural parameters (scholarship, number of children, marital status). Our data show that a greater number of S-carriers (n=60) than patients carrying the LL-genotype (n=33) attempted suicide (²=9.76, d.f.=1, P=0.002). Moreover, these patients attempted suicide more frequently (number of suicide attempts per attempter, 1.88 1.1 vs 1.61.1: t=2.97, P=0.008; respectively for S-carriers and LL-carriers). S-carriers had greater LSR scores (>2) and used violent means more frequently (Table 1). Suicidal intention was also greater in patients carrying the S-allele (17.534.46 vs 14.44.7: t=3.18, P=0.001). In S-carriers, LL-carriers as reference, the odds ratio were 2.34 (95% CI (1.32–4.15)), 2.44 (95% CI (0.93–6.53)) and 3.97 (95% CI(1.37–11.91)), respectively, to number of suicide attempts, lethality greater than 2 and violent suicide attempt.

Table 1 - Suicidal behavior characteristics in patients subgrouped by genotypes.

Full table

Our most important finding was the association between the S-allele with suicidal behavior. Indeed, these data are remarkable because they are independent of the clinical diagnosis and also the demographic and sociocultural parameters investigated.

Brazilian population is very heterogeneous and the genotypic distribution of both patients and controls were not in Hardy–Weinberg's equilibrium. Ethnic origin (African-Brazilian and Caucasian-Brazilian) was not different among the studied groups. However, as recently shown, race as determined by physical evaluation is a poor predictor of genomic African ancestry in Brazil, and an ethnic stratification bias cannot be completely excluded.⁸

In our study, S-carriers not only made more suicide attempts over time, but they also displayed an enhancement of some aspects of the suicidal gesture like violence, lethality and intent. Investigation of the association of this allele in a larger sample of suicide attempters, investigating other dimensions like impulsivity and hostility and its relation with suicidal behavior are needed to better elucidate this point.