title: Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli.
abstract: BACKGROUND
  Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing.
  
  
  METHODS
  A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence.
  
  
  RESULTS
  We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing.
  
  
  CONCLUSIONS
  Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.
authors.affiliation: Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Lo Bianco
authors.forename: G
authors.initials: G
authors.lastname: Blasi
authors.forename: P
authors.initials: P
authors.lastname: Taurisano
authors.forename: A
authors.initials: A
authors.lastname: Di Giorgio
authors.forename: F
authors.initials: F
authors.lastname: Ferrante
authors.forename: G
authors.initials: G
authors.lastname: Ursini
authors.forename: L
authors.initials: L
authors.lastname: Fazio
authors.forename: B
authors.initials: B
authors.lastname: Gelao
authors.forename: R
authors.initials: R
authors.lastname: Romano
authors.forename: A
authors.initials: A
authors.lastname: Papazacharias
authors.forename: G
authors.initials: G
authors.lastname: Caforio
authors.forename: L
authors.initials: L
authors.lastname: Sinibaldi
authors.forename: T
authors.initials: T
authors.lastname: Popolizio
authors.forename: C
authors.initials: C
authors.lastname: Bellantuono
authors.forename: A
authors.initials: A
authors.lastname: Bertolino
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism / Q000503:physiopathology; D000704:Analysis of Variance; D001931:Brain Mapping; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004644:Emotions / Q000502:physiology*; D005149:Facial Expression; D005260:Female; D007839:Functional Laterality; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D035781:Siblings
chemical_list: D002394:Catechol O-Methyltransferase; D004298:Dopamine