TY - JOUR
T1 - The effects of gender and catechol O-methyltransferase (COMT) Val108/158Met polymorphism on emotion regulation in velo-cardio-facial syndrome (22q11.2 deletion syndrome)
T2 - An fMRI study
AU - Coman, Ioana L.
AU - Gnirke, Matthew H.
AU - Middleton, Frank A.
AU - Antshel, Kevin M.
AU - Fremont, Wanda
AU - Higgins, Anne Marie
AU - Shprintzen, Robert J.
AU - Kates, Wendy R.
N1 - Funding Information:
This work was supported in part by the following grants to Dr. Kates: NIH R01 MH64824 , the National Alliance for Research in Schizophrenia and Depression (NARSAD) , and the Hendricks Foundation at SUNY Upstate Medical University . We thank Gwen Tillapaugh-Fay, Kelly Wallace, and Chris McCarthy for assisting with the fMRI data acquisition.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/11
Y1 - 2010/11
N2 - Velo-cardio-facial 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 gender-moderated 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-by-gender 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 did. 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.
AB - Velo-cardio-facial 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 gender-moderated 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-by-gender 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 did. 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.
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U2 - 10.1016/j.neuroimage.2010.01.094
DO - 10.1016/j.neuroimage.2010.01.094
M3 - Article
C2 - 20123031
AN - SCOPUS:77956228863
SN - 1053-8119
VL - 53
SP - 1043
EP - 1050
JO - NeuroImage
JF - NeuroImage
IS - 3
ER -