Abstract

Akt2 Gene is Associated with Anxiety and Neuroticism in Humans

Lucia Engeli, Marcel Delahaye, Stefan Borgwardt, Jurgen Gallinat, Daniel Muller, Marc Walter, Undine E Lang and Johannes Beck

Background: The exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of the highly associated anxiety and depressive disorders have not been identified. Akt2 is a key protein in the Phosphatidylinositide-3 (PI3K)/ Glycogen Synthase 3 kinase (GSK3) signaling pathway. This pathway is involved in Brain-Derived Neurotropic Factor (BDNF) signaling, fear memory, mood stabilization and action of several antidepressant drugs. In this study, we examined whether Akt2 Single Nuclear Polymorphisms (SNP) are associated with anxiety and depression associated personality traits.

Methods: Four hundred and sixty-three healthy participants completed a self-rating scale for anxiety traits (Spielberger Trait-Anxiety Inventory, STAI) and depressive personality traits (NEO-FFI). Four SNPs of the Akt2 gene (rs7247515, rs3730256, rs892118, rs11671439) were examined. Results: The ANCOVA showed that the dependent variable anxiety trait score was significantly affected by all four genotypes. The anxiety state score was a significant covariate in three genotypes. Neuroticism was influenced by three of the four examined genotypes.

Conclusion: We found a connection between different genotypes of the Akt2 gene and personality traits concerning anxiety and depression. These findings may be of importance for the understanding of the pathophysiology of depressive and anxiety disorders. Furthermore, Akt2 might be a potential novel therapeutic target in the treatment of those devastating mood disorders.