Brain functional abnormalities: a bridge between insulin signaling pathway gene polymorphisms and clinical cognition...

Obsessive-compulsive disorder (OCD) is a neurodevelopmental disorder, related to the central insulin signaling pathway. We investigate the relationship among central insulin signaling pathway gene polymorphisms/brain functional and clinical features in early-onset OCD(EO-OCD).

Candidate single nucleotide polymorphisms(SNPs) were genotyped and functional magnetic resonance imaging (FMRI) was performed EO-OCD and HCs. The MATRICS Consensus Cognitive Battery (MCCB) was used to evaluate those groups, and a mediating effect model to explore the relationship among polymorphisms-brain functional-clinical features in EO-OCD.

In EO-OCD, Rac GTPase-activating protein 1(RACGAP1) rs297941 was the key polymorphism to insulin signaling pathway. The amplitude of low-frequency fluctuation (ALFF) in right precuneus were greater in EO-OCD patients with an A allele than the GG genotype and the ALFF in right supramarginal and postcentral was decreased. The functional connectivity (FC) between right supramarginal and left/right supplementary motor areas, between right cerebellum and left angular of inferior parietal border, and between left angular and right cerebellum was enhanced in A allele. The mediating effect model showed rs297941 influenced information processing speed and obsessive thoughts through intermediary effects of ALFF in right postcentral and enhanced FC between left angular and right cerebellum.

Rs297941 was signiffcantly to EO-OCD. Abnormal FC/ALFF play a mediating role between rs297941 and information processing speed in EO-OCD.