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Med."],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:sec id=\"S0033291710001431_sec_a001\"><jats:title>Background<\/jats:title><jats:p>The Met allele of the catechol-<jats:italic>O<\/jats:italic>-methyltransferase (COMT) valine-to-methionine (Val<jats:sup>158<\/jats:sup>Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala\u2013prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the<jats:italic>COMT<\/jats:italic>Val<jats:sup>158<\/jats:sup>Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291710001431_sec_a002\"><jats:title>Method<\/jats:title><jats:p>We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (<jats:italic>n<\/jats:italic>=40), MDD and anxiety disorders (<jats:italic>n<\/jats:italic>=22) or no psychiatric diagnosis (<jats:italic>n<\/jats:italic>=25) and 50 healthy controls.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291710001431_sec_a003\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Irrespective of clinical phenotype, the Val<jats:sup>158<\/jats:sup>allele was associated with greater amygdala activation and the Met<jats:sup>158<\/jats:sup>allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met<jats:sup>158<\/jats:sup>allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291710001431_sec_a004\" sec-type=\"conclusion\"><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that the<jats:italic>COMT<\/jats:italic>Val<jats:sup>158<\/jats:sup>Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met<jats:sup>158<\/jats:sup>allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291710001431","type":"journal-article","created":{"date-parts":[[2010,7,29]],"date-time":"2010-07-29T11:08:21Z","timestamp":1280401701000},"page":"779-788","source":"Crossref","is-referenced-by-count":47,"title":["The impact of the Val<sup>158<\/sup>Met catechol-<i>O<\/i>-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives"],"prefix":"10.1017","volume":"41","author":[{"given":"G.","family":"Lelli-Chiesa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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