Neurocan genome-wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans.

摘要: Alterations of the brain extracellular matrix (ECM) can perturb structure and function networks like hippocampus, a key region in human memory that is commonly affected psychiatric disorders. Here, we investigated potential effects genome-wide risk variant NCAN gene encoding ECM proteoglycan neurocan (rs1064395) on performance, hippocampal cortical morphology young, healthy volunteers. We assessed verbal performance two cohorts (N = 572, 302) found reduced recall allele (A) carriers across both cohorts. In 117 participants, performed functional magnetic resonance imaging using novelty-encoding task with visual scenes. Risk showed higher false alarm rates during recognition, accompanied by inefficiently increased left activation. To assess rs1064395 morphology, voxel-based morphometry 420 participants from four independent lower grey matter density ventrolateral rostral prefrontal cortex carriers. silico eQTL analysis revealed SNP linked not only to expression itself, but also neighbouring HAPLN4 gene, suggesting more complex effect composition. Our results suggest A associated hippocampus-dependent function, variation Considering well-documented dysfunction bipolar disorder schizophrenia, our may reflect an intermediate phenotype which contributes disease risk.