Childhood adversities and the 5-HTTLPR polymorphism are involved in the aetiology of substance use disorders though findings exploring the existence of a gene-environment interaction were inconclusive.
Using the genotype data of 55 studies (7999 cases, 8264 controls, and 676 families or parent-offspring trios) published in the past 15 years, we have conducted comprehensive meta-analyses to examine the associations of the 5-HTTLPR and STin2 polymorphisms with substance use disorder.
SUD and NSUD disorders were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Health Disorders criteria using the Psychiatric Research Interview for Substance and Mental Disorders.Incidence Rates (IR) are presented.The 5-HTTLPR polymorphism was analyzed.Hardy-Weinberg equilibrium was studied.
We found three candidate genes associated with both BD and TUD (COMT, SLC6A3, and SLC6A4) and commonality analysis suggests that these genes interact in predisposing psychiatric and substance use disorders.
A total of 110 adult patients with ASD (n=61) or ADHD (n=49) with or without a lifetime history of SUD participated in a study in which we genotyped polymorphisms in five known candidate genes for (one of) the disorders, i.e. the 5HTTLPR in SLC6A4/5-HTT, rs1800497 (TaqIA C>T) in DRD2, rs7794745 in CNTNAP2, rs1843809 in TPH2, and rs6565113 in CDH13.
On the whole, our preliminary data suggest that the association between 5-HT transporter polymorphism and psycho-stimulant use may be mediated by mother-child relationship and parental attachment perception, both being environmental and genetic factors involved in the proneness to substance use disorders, particularly in aggressive-antisocial individuals.
Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with substance use disorders, particularly in the subjects with comorbid antisocial behavior, and with temperament and personality traits at risk for substance abuse.
Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased risk for substance use disorders, particularly in the subjects with more consistent aggressiveness and impulsiveness.