The effect of genome-wide supported variants in CACNA1C and NRGN on functional correlates of episodic memory encoding and retrieval

Abstract

Objective: Genetic studies implicated variation in NRGN and CACNA1C as a susceptibility locus for bipolar disorder, schizophrenia and major depression. Method: We investigated the influence of the CACNA1C single nucleotide polymorphism (SNP) rs1006737 and rs12807809 of NRGN on functional correlates of episodic memory encoding and retrieval. Brain activation was measured with functional magnetic resonance imaging (fMRI) during an episodic memory encoding and retrieval task in 94 healthy individuals who were genotyped for both variants. Results: In the fMRI experiment, while there were no differences in behavioral performance, neural activation-mainly in the superior frontal gyrus and inferior and middle temporal gyrus – was associated with CACNA1C genotype during encoding and retrieval. For NRGN, differential brain activation was evident in the anterior cingulate cortex for the encoding and posterior cingulate regions during retrieval. Conclusions: Our data suggest that both variants influence the neural systems related to memory processes: Brain activations during encoding and retrieval of new material might compensate for otherwise insufficient performance. These findings are in line with results of imaging studies in affective disorder and schizophrenia. It may explain some of the brain activation variation found in these disorders and healthy subjects.