The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

G. Lelli-Chiesa, M.J. Kempton, J. Jogia, R. Tatarelli, P. Girardi, J. Powell, D.A. Collier, S. Frangou

Research output: Contribution to journalArticlepeer-review


Background - The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal 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 COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.
Method - 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 (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.
Results - Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met 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 Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.
Conclusions - Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

Original languageEnglish
Pages (from-to)779-788
Number of pages10
JournalPsychological Medicine
Issue number4
Early online date29 Jul 2010
Publication statusPublished - Apr 2011

Bibliographical note

Copyright © Cambridge University Press 2010


  • anxiety disorders
  • sadness
  • major depressive disorder
  • genetic
  • facial affect
  • COMT
  • bipolar disorder

Fingerprint Dive into the research topics of 'The impact of the Val<sup>158</sup>Met catechol-<em>O</em>-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives'. Together they form a unique fingerprint.

Cite this