Serotonin system gene polymorphisms are associated with impulsivity in a context dependent manner

Abstract

Impulsivity is a risk factor for adverse outcomes and characterizes several psychiatric disorders and risk for suicide. There is strong evidence that genetic variation influences individual differences in impulsivity, but the details are not yet understood. There is growing interest in better understanding the context dependency of genetic effects that is reflected in studies examining gender specificity, gene×environment interaction and epistasis (gene-gene interaction). In a cross-sectional study we examined whether polymorphisms in six serotonin system candidate genes and the experience of early life trauma (age 0-12) were associated with individual differences in impulsivity in a non-clinical sample of Caucasian university students (N=424). We specifically tested potential gender specific, gene-gene, and gene×environment (early life trauma) effects. In our main analyses with Barratt Impulsiveness Scale (BIS-11) total score, there were significant (i.e. p<.01 and False Discovery Rate <.10) interactions between (1) gender and TPH2 (rs1386483) genotype; (2) gender and HTR2A (rs6313) genotype; and epistatic interactions among (3) 5-HTTLPR and MAOA uVNTR; (4) 5-HTTLPR and rs6313 and (5) HTR1B (rs6296) and rs6313 genotypes. Our results strongly support the explicit investigation of context dependent genetic effects on impulsivity and may help to resolve some of the conflicting reports in the literature.

The impact of serotonin receptor 1A and 2A gene polymorphisms and interactions on suicide attempt and suicide risk in depressed patients with insufficient response to treatment – a European multicentre study

“…It has been supposed that complex behaviours, such as suicidal behaviour, likely show gene-gene interactions (Stoltenberg et al, 2012). Epistatic effects between genes of monoamines and GABA have been found previously in female suicide attempters (Fernández-Navarro et al, 2012).…”

Serotonin 5-HT2 Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

“…Several SNPs in the promoter or coding regions of the genes for 5-HT 2A R (HTR 2A ) and 5-HT 2C R (HTR 2C ) have been shown to associate with personality traits, psychiatric conditions, and response to psychiatric medications such as atypical antipsychotics and antidepressants. Impulsivity has been Cocaine, 5-HT 2 Receptors, and Dopamine associated with genotypes that predict reduced 5-HT function (Bjork et al, 2002;Bevilacqua et al, 2010;Stoltenberg et al, 2012;Bevilacqua and Goldman, 2013). The HTR 2A A(-1438)G SNP was associated with response inhibition in two specific behavioral tasks in normal subjects (Nomura et al, 2006) and impulsive behavior in bulimia (Bruce et al, 2005).The HTR 2A T10 2C SNP is associated with impulse control in cocaine-dependent subjects (Bjork et al, 2002).…”

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

“…Identification and validation of single nucleotide polymorphisms ( SNPs ) that predict impulsivity, cue reactivity or treatment success could also be useful in guiding prevention efforts (Ducci and Goldman, 2012). Impulsivity has been associated with genotypes that predict reduced 5-HT function (Bevilacqua, et al, 2010; Bevilacqua and Goldman, 2013; Bjork, et al, 2002; Stoltenberg, et al, 2012) and we have recently demonstrated that cocaine-dependent subjects who carry a SNP in the HTR2C (rs6318) (Lappalainen, et al, 1995) predicted to alter 5-HT 2C R functionality (Brasch-Andersen, et al, 2011; Kuhn, et al, 2004; Okada, et al, 2004; Walstab, et al, 2011), exhibit significantly higher attentional bias on the cocaine-word Stroop task. As convergent evidence links genotypes to phenotypes important in addictive processes, it will be possible to best understand the shared genetic liability for impulsivity and cue reactivity, and to integrate this information into more effective clinical care for afflicted patients.…”