The dopamine D2 receptor gene DRD2 and the nicotinic acetylcholine receptor gene CHRNA4 interact on striatal gray matter volume: evidence from a genetic imaging study.

Dopaminergic activity is modulated by acetylcholine with relevance for cognitive functioning, as shown by pharmacological work in a rodent model. In humans, the two transmitter systems' joint effort on cognition has been described on the molecular genetic level: DRD2 rs6277, a single nucleotide polymorphism (SNP) on the dopamine D2 receptor gene and CHRNA4 rs1044396, a SNP on the nicotinic acetylcholine receptor gene interact on visuo-spatial and phonological working memory. The present study uses structural MRI and voxel based morphometry to extend this behavioral work to an intermediate phenotype on the neural level. We found significantly reduced gray matter volume in the right putamen in carriers of the DRD2 C/C and CHRNA4 T/T groups. This genotype combination has previously proven to be beneficial for working memory capacity. Results are in line with the idea that the two genes jointly influence the gating signals from subcortical structures to the prefrontal cortex.