Variation rs6971 in the Translocator Protein Gene (TSPO) Is Associated with Aggressiveness and Impulsivity but Not with Anxiety in a Population-Representative Sample of Young Adults

Abstract

Expression of the 18-kDa translocator protein (TSPO), originally identified as a peripheral benzodiazepine receptor, has been found to be altered in several psychiatric disorders. A common single nucleotide polymorphism (rs6971) in the TSPO gene leads to an amino acid substitution, Ala147Thr, which dramatically alters the affinity with which TSPO binds drug ligands. As cholesterol also binds TSPO in the same transmembrane domain, it is suggested that this substitution may impair the ability of TSPO to bind or import cholesterol, and hence may affect steroid synthesis and hypothalamic-pituitary-adrenal function. The analysis was carried out on older birth cohort (n = 655) of the longitudinal Estonian Children Personality, Behavior and Health Study sample. Anxiety, aggressive behavior, impulsiveness, and history of stressful life events were self-reported in various data collection waves. Psychiatric assessment of lifetime prevalence of anxiety disorders was carried out at 25 years of age by experienced clinical psychologists. TSPO rs6971 was genotyped in all participants. TSPO rs6971 was not associated with self-reported levels of anxiety or lifetime prevalence of anxiety disorders. However, participants homozygous for the minor A allele displayed the highest aggressiveness and dysfunctional impulsivity scores. The positive, adaptive aspect of impulsivity was sensitive to stressful life events, as the AA genotype was associated with functional impulsivity only when the participants had experienced a low number of stressful life events during childhood. TSPO rs6971 polymorphism may be related to development of aggressiveness and impulsivity by adulthood, regardless of the participants’ gender.