title: Catechol-O-methyltransferase Val(108/158)Met polymorphism affects fronto-limbic connectivity during emotional processing in bipolar disorder.
abstract: Catechol-O-methyltransferase (COMT) inactivates catecholamines, Val/Val genotype was associated to an increased amygdala (Amy) response to negative stimuli and can influence the symptoms severity and the outcome of bipolar disorder, probably mediated by the COMT polymorphism (rs4680) interaction between cortical and subcortical dopaminergic neurotransmission. The aim of this study is to explore how rs4680 and implicit emotional processing of negative emotional stimuli could interact in affecting the Amy connectivity in bipolar depression. Forty-five BD patients (34 Met carriers vs. 11 Val/Val) underwent fMRI scanning during implicit processing of fearful and angry faces. We explore the effect of rs4680 on the strength of functional connectivity from the amygdalae to whole brain. Val/Val and Met carriers significantly differed for the connectivity between Amy and dorsolateral prefrontal cortex (DLPFC) and supramarginal gyrus. Val/Val patients showed a significant positive connectivity for all of these areas, where Met carriers presented a significant negative one for the connection between DLPFC and Amy. Our findings reveal a COMT genotype-dependent difference in corticolimbic connectivity during affective regulation, possibly identifying a neurobiological underpinning of clinical and prognostic outcome of BD. Specifically, a worse antidepressant recovery and clinical outcome previously detected in Val/Val patients could be associated to a specific increased sensitivity to negative emotional stimuli.
authors.affiliation: IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy; CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy; Department of Human Studies, Libera Università Maria Ss. Assunta, Roma, Italy. Electronic address: b.vai@hotmail.it.
authors.forename: B
authors.initials: B
authors.lastname: Vai
authors.affiliation: IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Riberto
authors.affiliation: IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy; CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Poletti
authors.affiliation: IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy; CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Bollettini
authors.affiliation: IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Lorenzi
authors.affiliation: IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Colombo
authors.affiliation: IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy; CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Benedetti
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism; D001714:Bipolar Disorder / Q000235:genetics / Q000523:psychology; D001931:Brain Mapping / Q000379:methods; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D063132:Connectome / Q000379:methods; D004644:Emotions / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D011569:Psychiatric Status Rating Scales
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Bipolar; COMT; Depression; Emotion; Functional connectivity