Genetic variation in schizophrenia-risk-gene dysbindin 1 modulates brain activation in anterior cingulate cortex and right temporal gyrus during language production in healthy individuals.

ABSTRACT

Genetic variation in dysbindin 1 (DTNBP1) gene region tagged by SNP rs1018381 exhibits a linkage with cognitive deficits in patients with schizophrenia and healthy subjects. Language production deficits are core features of schizophrenia with more impairment in semantic than lexical verbal fluency tasks. We investigated the link between brain activation and DTNBP1 SNP rs1018381 during semantic verbal fluency task in a German healthy population. 46 healthy subjects genotyped for SNP rs1018381 status were divided in heterozygous risk-allele carriers (T/C) and homozygous non-carriers (C/C). Neural correlates of semantic verbal fluency were investigated with functional magnetic resonance imaging (fMRI). Stronger right hemispherical brain activation in anterior cingulate gyrus (BA 24), superior (BA 22, 38) and middle (BA 21) temporal gyrus was observed in the carriers compared to non-carriers. Brain activations occurred in the absence of task performance differences. No significant correlations were found between personality traits and brain activation differences. The results point to an influence of genetic variation in DTNBP1 gene region tagged by SNP rs1018381 on neural correlates of language production. Carriers may exhibit higher processing efforts to reach the same behavioural performance as non-carriers as reflected in activation of schizophrenia-related regions.