The effects of gender and Catechol O-Methyltransferase (COMT) Val108/158Met polymorphism on emotion regulation in Velo- Cardio-Facial Syndrome (22q11.2 Deletion Syndrome): a fMRI study

Velocardiofacial syndrome (VCFS) is caused by a micro-deletion of over 40 genes at the q11.2 locus of chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. COMT, one of the genes located in the deleted region, has been considered as a major candidate gene for genetic susceptibility in psychiatric diseases. Its functional polymorphism Val108/158Met has been shown to affect prefrontal function and working memory and has been associated with emotional dysregulation. We utilized a functional magnetic resonance imaging (fMRI) event-related paradigm to asses COMT genotype and gendermoderated effects on the neural activation that are elicited by viewing emotionally salient images charged with pleasant, unpleasant, and neutral content. Since estrogen down-regulates COMT activity resulting in lower COMT activity in women than men, we hypothesized an allele-bygender interaction effect on neural activation. Participants included 43 VCFS individuals (Val/ Male=9, Val/Female=17, Met/Male=9, Met/Female=8). We observed a gender effect on processing positive emotions, in that girls activated the cingulate gyrus more than boys. We further observed a significant gender-by-allele interaction effect on neural function specific to the frontal lobe during the processing of pleasant stimuli, and specific to limbic regions during the processing of unpleasant stimuli. Our results suggest that in VCFS, the effect of the COMT Val108/158Met polymorphism is moderated by gender during the processing of emotional stimuli and could contribute to the understanding of the way in which this COMT polymorphism affects vulnerability to neuropsychiatric disorders. © 2010 Elsevier Inc. All rights reserved. *Corresponding author: Phone: 315-464-3296; Fax: 315-464-3263; [email protected]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Neuroimage. Author manuscript; available in PMC 2011 November 15. Published in final edited form as: Neuroimage. 2010 November 15; 53(3): 1043–1050. doi:10.1016/j.neuroimage.2010.01.094. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript