The impact of dystrobrevin-binding protein 1 (DTNBP1) on neural correlates of episodic memory encoding and retrieval

Abstract

Episodic memory impairment is a frequently reported symptom in schizophrenia. It has been shown to be associated with reduced neural activity of the hippocampus and prefrontal cortex. Given the high heritability of schizophrenia the question arises if alterations in brain activity are modulated by susceptibility genes and might be detectable in healthy risk allele carriers. The present study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 (P1578) of the dystrobrevin-binding protein 1 (DTNBP1) on brain activity in 84 healthy subjects assessed by functional magnetic resonance imaging (fMRI) while they performed an episodic memory task comprising encoding and retrieval of faces. During encoding, the group of risk allele carriers (n = 29) showed enhanced neural activity in the left middle frontal gyrus (BA 11) and bilaterally in the cuneus (BA 17, 7) when compared with the nonrisk carrier group (n = 55). During retrieval, the risk group (compared to the non risk group) showed increased right hemispheric neural activity comprising the medial frontal gyrus (BA 9), inferior frontal gyrus (BA 9), and inferior parietal lobule (BA 40). Since there were no behavioral performance differences, increased neural activity of the risk group might be interpreted as a correlate of higher effort or differing cognitive strategies in order to compensate for a genetically determined slight cognitive deficit. Interestingly, the laterality of increased prefrontal activity is in accordance with the well known hemispheric encoding/retrieval asymmetry (HERA) model of episodic memory. © 2009 Wiley-Liss, Inc.