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.

Keywords:

• Aggressiveness
• anxiety
• benzodiazepine receptor
• impulsivity
• TSPO

Acknowledgments

The author is grateful to the national and international reseach partners, the participants of the ECPBHS, and to the whole ECPBHS Study Team.

Conflicts of interest

The author declares that there is no conflict of interest.

Data availability statement

The data that support the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

Additional information

Funding

This work was supported by grants from the European Union's Horizon 2020 research and innovation programmes under grant agreements no. 667302 (CoCA) and no. 728018 (Eat2beNICE) and European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 602805 (Aggressotype).

Notes on contributors

Mariliis Vaht

Mariliis Vaht, Research Fellow of Human Genomics at Institute of Genomics, University of Tartu, Estonia. PhD in psychology. Area of research: genetic and genomic factors in psychological traits and disorders using longitudinal population-based samples. The focus in main publications has been problematic alcohol use and aggressive behavior and also birth cohort effects in behavioral genetics.