CYP2C19 expression modulates affective functioning and hippocampal subiculum volume-a large single-center...

Area of Science:

• Neuroscience
• Pharmacogenomics
• Psychiatry

Background:

• Contradictory findings exist regarding CYP2C19 genotype, depressive symptoms, and hippocampus volume.
• Investigating these associations in a large, community-dwelling adult population is crucial.

Purpose of the Study:

• To examine CYP2C19 genotype-related behavioral and brain anatomy patterns.
• To determine associations between CYP2C19 metabolizer status and mood phenotypes.
• To investigate potential links with brain imaging indices, including hippocampus volume.

Main Methods:

• Utilized data from the large-scale Colaus|PsyCoLaus cohort (n=4152) and BrainLaus imaging cohort (n=1187).
• Employed comprehensive psychometry and advanced magnetic resonance imaging (MRI) techniques (diffusion and relaxometry).
• Statistical models tested associations between CYP2C19 metabolizer status and mood/imaging data.

Main Results:

• A significant association was found between CYP2C19 genotype and lifetime affective status, with higher functioning in poor metabolizers, primarily driven by female participants.
• No significant difference in total hippocampus volume was observed between poor metabolizers and other metabolizer groups.
• Poor metabolizers showed increased right subiculum volume within the hippocampus (pFDRcorrected=0.036).

Conclusions:

• The study supports an association between mood phenotype and CYP2C19 genotype.
• Evidence for widespread hippocampus volume differences related to CYP2C19 genotype was not found.
• A specific increase in right subiculum volume in poor metabolizers warrants further investigation.