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Catechol-O-methyltransferase Val(108/158)Met polymorphism affects fronto-limbic connectivity during emotional processing in bipolar disorder

Published online by Cambridge University Press:  03 February 2017

B. Vai ,
M. Riberto ,
S. Poletti ,
I. Bollettini ,
C. Lorenzi ,
C. Colombo  and
F. Benedetti
B. Vai*
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
M. Riberto
Affiliation:
IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy
S. Poletti
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
I. Bollettini
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
C. Lorenzi
Affiliation:
IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy
C. Colombo
Affiliation:
IRCCS Ospedale San Raffaele, Department of Clinical Neurosciences, Milan, Italy
F. Benedetti
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
*
⁎Corresponding author. Department of Clinical Neurosciences, Istituto Scientifico Ospedale San Raffaele, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy. Tel.: +39 02 264 331 56; fax: +39 02 264 332 65. E-mail address: [email protected] (B. Vai).
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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.

Keywords

Functional connectivityCOMTDepressionBipolarEmotion
Type
Original article
Information
European Psychiatry , Volume 41 , Issue 1 , March 2017 , pp. 53 - 59
Copyright
Copyright © European Psychiatric Association 2017

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