Elsevier

Journal of Psychiatric Research

Volume 61, February 2015, Pages 52-56
Journal of Psychiatric Research

ABCB1 gene polymorphisms and violent suicide attempt among survivors

https://doi.org/10.1016/j.jpsychires.2014.12.005Get rights and content

Highlights

  • The T allele in the three most common ABCB1 SNPs was most frequent among individuals who dead by using violent suicide methods.

  • Present result show a higher frequency of suicide attempters using violent methods among ABCB1 haplotype (1236TT-2677TT-3435 TT) carriers.

  • This ABCB1 haplotype increased the risk more than three times among women attempting a violent suicide for the first time.

Abstract

Introduction

Those suicide attempters that choose violent methods dramatically diminish the possibility of survival. Completed suicide using violent means, which is common among first-time suicide attempters, was recently found to be more likely among T allele carriers in the three most common ABCB1 SNPs, encoding for P-gp. Thus, this study examined, for the first time, whether these ABCB1 SNPs were associated with the use of violent means among survivors of a suicide attempt.

Material and methods

Suicide attempters (n = 578, 87.4% women; of whom 16.6% committed a violent intent) were genotyped for exonic SNPs in the ABCB1 (C1236T, G2677T/A, C3435T). The relations of the three genotypes and of the TTT haplotype with the use of a violent suicide method were evaluated separately. The impact of confounds on these variables was controlled.

Results

A higher frequency (p = 0.02) of suicide attempters using violent methods was found among those carrying the ABCB1 haplotype (1236TT-2677TT-3435TT). Since gender and number of previous suicide attempts were identified as confounds, the relation was tested in the subset of women who were first-time attempters or second- and more-time attempters. The ABCB1 haplotype increased the risk more than three times in those women attempting a violent suicide for the first time (OR = 3.6; CI95%: 1.08–12.09; p = 0.04).

Discussion

The ABCB1 haplotype (1236TT-2677TT-3435TT) was related to the use of a violent suicide attempt method. Genotyping for these three ABCB1 SNPs may be helpful to detect people at risk of first suicide intents using violent methods.

Introduction

Suicidal behavior is a major public health problem and remains one of the leading causes of death especially in the western world. Many psychiatrists (50–70%) report having lost at least one patient to suicide (Alexander et al., 2000, Courtenay and Stephens, 2001, Chemtob et al., 1988), like other mental health professionals (Linke et al., 2002). WHO estimates that about 1.53 million people will die from suicide worldwide in 2020 and 10–20 times more people will attempt suicide (WHO, 1999).

The term “suicide attempt” covers a very broad array of self-injurious behaviors from highly lethal or violent to others with a small risk of physical harm. Those suicide attempters that use violent methods involving firearms, drowning, deep-cutting, jumping or hanging represent a sub-population of major interest. Violent suicide attempters show characteristics that appear closer to those of suicide completers than to the rest of suicide attempters (Giner et al., 2014), probably because they have an increased risk of eventual suicide completion (Runeson et al., 2010). For example, among the most common violent methods of suicide in men and women are hanging, or manual strangulation or suffocation (Biddle et al., 2008), which present an estimated fatality rate of over 70% (Gunnell et al., 2005).

While suicide appears preventable by increasing safety measures or reducing access to methods, it poses a challenge when occurs in private households with everyday items (Bennewith et al., 2005) making it unpredictable; hence it is essential to identify biomarkers for the subset of suicide attempters characterized by the choice of violent methods. Moreover, as the vast majority of completed suicides occur on the very first attempt (Isometsa and Lonnqvist, 1998), providing markers of violent suicidal behavior in subjects without a past history of suicide attempts would be crucial in establishing prevention strategies. This is in agreement with the research agenda of The National Action Alliance for Suicide Prevention that specifically proposes to identify and target subgroups at greatest risk (Pringle et al., 2013). In keeping with this strategy, since the seminal works of Asberg et al., in 1976 (Asberg et al., 1976), several studies have tried to identify different biomarkers associated with the risk of violent suicidal behavior in relation to neuropsychological impairment (Jollant et al., 2005), aggressive behavior (Lindqvist et al., 2011), fetal and childhood development (Blasco-Fontecilla et al., 2013), genetics (Courtet et al., 2001), etc.

Completed suicide using violent means has been recently associated with the ABCB1 gene (Boiso Moreno et al., 2013) encoding for the transporter P glicoprotein (P-gp). P-gp is relevant for the transport of clinically useful drugs and xenobiotics but also of endogenous substances (lipids, steroids, peptides, bilirrubine, glucocorticoids) across the blood brain barrier. It protects against the entrance of toxic substances in the CNS and favors their elimination transporting them into the gut, urine, bile, etc. (Hodges et al., 2011). Therefore, given the role of P-gp in the exogenous and endogenous metabolism, it has the potential to influence both drug treatment response and behavior, which may support its implication in violent suicidal behavior.

A higher frequency of the T allele at the three most common genetic variants of ABCB1 (C1236T, G2677T/A, C3435T) was found among individuals who committed suicide as compared with non-suicidal deaths (natural, accident or undetermined with the exception of intoxications). This association of the T allele with suicide was even more significant for the subpopulation of individuals who had used a violent method (hanging, strangulation, suffocation, gunshot, jumping from heights, and cutting), and for males too, although males were overrepresented comprising 76% of the sample (Boiso Moreno et al., 2013).

The 2677T allele in the ABCB1 gene has been also associated with increased suicidal ideation during antidepressant treatment in outpatients with a diagnosis of major depression (Perroud et al., 2011), independently of the type of the drug used during the study. Suicidal ideation is one of the symptoms for depression, which is one of the psychiatric illnesses reported to carry the strongest risk for suicide (Qin, 2011). Consistently, carriers of the ABCB1 haplotype 1236T-3435T were more frequently found among a large population of Japanese patients with Major Depression than in healthy controls (Fujii et al., 2012). Additionally, the ABCB1 1236T allele has been associated with increased levels of depression among individuals with a moderate depressive episode (Lin et al., 2011).

In the light of above information suggesting that carrying the T allele in the C1236T, G2677T/A, C3435T ABCB1 polymorphisms may increase the risk for completing a suicide of a violent nature as shown in a Swedish forensic population (Boiso Moreno et al., 2013), we have examined, for the first time, whether the T allele is related to the violence of the suicide attempt. Furthermore, since the T allele has been also associated with psychiatric conditions, especially with depression, the present study will control for the potential effect of these and other confounds like history of suicide attempts potentially associated with both variables of interest.

Section snippets

Material and methods

Survivors of a suicide attempt (n = 578; 87.4% women) with a mean age of 37.2 (±12.1; range 18–74) were evaluated in a specialized unit of the Montpellier University Hospital. Of the total sample, 50% reported university studies. Marital status was mostly single (40.5%), married (34.5%), and divorced (16.2%). The majority of the present population of suicide attempters had multiple DSM-IV Axis I mental disorders as assessed by the Mini-International Neuropsychiatric Interview (MINI) or

Evaluation of suicide

Of the total, 96 (16.6%) performed a violent suicide attempt. The present suicide attempt was the first one for 208 (35.9%), and the second for 165 (28.5%), whereas the rest had attempted more than two times. Almost half of the population (n = 264; 45.7%) had family history of suicide.

Evaluation of ABCB1 SNPs

The ABCB1 SNPs of the present population were not in H-W-E (Table 1). Furthermore, no associations were found between carriers of the T allele in each of these SNPs and the use of a violent suicide method.

The

Discussion

The present study shows a relationship between violent suicide attempts and genetic variation in the ABCB1 gene. In particular, the use of a violent suicide attempt method appears more frequent among those carrying the haplotype 1236TT-2677TT-3435TT and less frequently used by those that do not carry the T allele at these SNPs. This finding is of major relevance since violent suicide attempters present an increased risk of lethality (Gunnell et al., 2005) and suicide completion (Runeson et al.,

Role of the funding source

All of the authors were salaried by their institution at time of manuscript preparation. None of the authors received compensation for authorship of the manuscript.

Author contributions

*SG with IJ and PC wrote the clinical protocol, created the clinical database, oversaw collection of the data, and critically revised of the manuscript. EPLL with AD, MEGN and ALL performed the genetic and data analyses, and wrote the first draft, draft review and revision of the manuscript.

*All authors have approved the final version of the manuscript.

Conflict of interest

None has competing interests to declare.

Acknowledgments

This work was supported in part by Union Europea Fondo Social Europeo (FEDER/FSE) and Gobierno de Extremadura Consejería de Economía, Competitividad e Innovación (IB13186 and PD10199). CHU Montpellier (PHRC UF 7653), Agence Nationale de la Recherche (ANR NEURO 2007 “GENESIS”).

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