Influence of the serotonin transporter gene polymorphism, cannabis and childhood sexual abuse on phenotype of bipolar disorder: A preliminary study

Abstract

Objective The gene coding for the 5-HT transporter ( 5-HTT) is considered as a candidate gene for bipolar disorder, either as a “vulnerability” or as a “modifying the phenotype” gene. Psychotic symptoms occur at least once in one bipolar patient out of two, the relevant risk factors being insufficiently understood. The gene × environment interaction approach offers the opportunity to disentangle the latter, including childhood sexual abuse and cannabis abuse. Methods We investigated the 5-HTTLPR of the 5-HTT gene (G) and the presence of childhood sexual abuse and cannabis comorbidity (E) in 137 bipolar patients with (versus without) lifetime psychotic symptoms. Results The short allele and cannabis abuse were significantly more frequent among patients with psychotic symptoms than in those without ( p = 0.01 and p = 0.004, respectively), while childhood sexual abuse was not. Complex interactions were found between presence of the short allele, cannabis abuse or dependence and childhood sexual abuse. Conclusions The short allele of the 5-HTTLPR polymorphism of the 5-HTT gene was a risk factor for psychotic symptoms in bipolar disorder in the present sample, directly but also indirectly, through the presence of cannabis abuse or dependence, as an exacerbating factor heightening psychotic symptoms.