title: 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.
abstract: 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.
  
  
  METHODS
  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 Met158 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.
authors.affiliation: Section of Neurobiology of Psychosis, Institute of Psychiatry, King's College London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Lelli-Chiesa
authors.forename: M J
authors.initials: MJ
authors.lastname: Kempton
authors.forename: J
authors.initials: J
authors.lastname: Jogia
authors.forename: R
authors.initials: R
authors.lastname: Tatarelli
authors.forename: P
authors.initials: P
authors.lastname: Girardi
authors.forename: J
authors.initials: J
authors.lastname: Powell
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
authors.forename: S
authors.initials: S
authors.lastname: Frangou
mesh_terms: D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000503:physiopathology*; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D004292:Dominance, Cerebral / Q000235:genetics / Q000502:physiology; D004644:Emotions / Q000502:physiology*; D005149:Facial Expression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology; D010100:Oxygen / Q000097:blood*; D010364:Pattern Recognition, Visual / Q000502:physiology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011930:Reaction Time / Q000502:physiology; D055815:Young Adult
chemical_list: D002394:Catechol O-Methyltransferase; D010100:Oxygen