A genome‐wide supported psychiatric risk variant in NCAN influences brain function and cognitive performance in healthy subjects. Issue 1 (13th September 2014)

• Record Type: Journal Article
• Authors: Raum, Heidelore; Dietsche, Bruno; Nagels, Arne; Witt, Stephanie H.; Rietschel, Marcella; Kircher, Tilo; Krug, Axel
• Is Part Of: Human brain mapping. Volume 36:Issue 1(2015:Jan.)
• Page Start: 378
• Page End: 390
• Publication Date: 2014-09-13
• Subjects: Brain mapping -- Periodicals; 611.81
• DOI: 10.1002/hbm.22635
• Languages: English
• ISSNs: 1065-9471

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>The A allele of the single nucleotide polymorphism (SNP) rs1064395 in the <italic>NCAN</italic> gene has recently been identified as a susceptibility factor for bipolar disorder and schizophrenia. <italic>NCAN</italic> encodes neurocan, a brain‐specific chondroitin sulfate proteoglycan that is thought to influence neuronal adhesion and migration. Several lines of research suggest an impact of <italic>NCAN</italic> on neurocognitive functioning. In the present study, we investigated the effects of rs1064395 genotype on neural processing and cognitive performance in healthy subjects. Brain activity was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 110 healthy subjects who were genotyped for the <italic>NCAN</italic> SNP rs1064395. Participants additionally underwent comprehensive neuropsychological testing. Whole brain analyses revealed that <italic>NCAN</italic> risk status, defined as AA or AG genotype, was associated with a lack of task‐related deactivation in a large left lateral temporal cluster extending from the middle temporal gyrus to the temporal pole. Regarding neuropsychological measures, risk allele carriers demonstrated poorer immediate and delayed verbal memory performance when compared to subjects with GG genotype. Better verbal memory performance was significantly associated with greater deactivation of the left temporal cluster during the fMRI task in subjects with GG genotype. The current data demonstrate that common genetic variation in <italic>NCAN</italic> influences both neural processing and cognitive performance in healthy subjects. Our study provides new evidence for a specific genetic influence on human brain function. <italic>Hum Brain Mapp, 36:378–390, 2015</italic>. © <bold>2014 Wiley Periodicals, Inc.</bold></p> </abstract>