Effects of DARPP-32 Genetic Variation on Prefrontal Cortex Volume and Episodic Memory Performance

Despite evidence of a fundamental role of DARPP-32 in integrating dopamine and glutamate signaling, studies examining gene coding for DARPP-32 in relation to neural and behavioral correlates in humans are scarce. Post mortem findings suggest genotype specific expressions of DARPP-32 in the dorsal frontal lobes. Therefore, we investigated the effects of genomic variation in DARPP-32 coding on frontal lobe volumes and episodic memory. Volumetric data from the dorsolateral (DLPFC), and visual cortices (VC) were obtained from 61 younger and older adults (♀54%). The major homozygote G, T, or A genotypes in single nucleotide polymorphisms (SNPs: rs879606; rs907094; rs3764352, the two latter in complete linkage disequilibrium), at the DARPP-32 regulating PPP1R1B gene, influenced frontal gray matter volume and episodic memory (EM). Homozygous carriers of allelic variants with lower DARPP-32 expression had an overall larger prefrontal volume in addition to greater EM recall accuracy after accounting for the influence of age. The SNPs did not influence VC volume. The genetic effects on DLPFC were greater in young adults and selective to this group for EM. Our findings suggest that genomic variation maps onto individual differences in frontal brain volumes and cognitive functions. Larger DLPFC volumes were also related to better EM performance, suggesting that gene-related differences in frontal gray matter may contribute to individual differences in EM. These results need further replication from experimental and longitudinal reports to determine directions of causality.