Interaction between catechol-O-methyltransferase (COMT) Val 158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli

L. Lo Bianco, G. Blasi, P. Taurisano, A. Di Giorgio, F. Ferrante, G. Ursini, L. Fazio, B. Gelao, R. Romano, A. Papazacharias, G. Caforio, L. Sinibaldi, T. Popolizio, C. Bellantuono, A. Bertolino

Research output: Contribution to journalArticle

13 Citations (Scopus)

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. Method 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.

Original languageEnglish
Pages (from-to)279-292
Number of pages14
JournalPsychological Medicine
Volume43
Issue number2
DOIs
Publication statusPublished - Feb 2013

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Catechol O-Methyltransferase
Schizophrenia
Genotype
Emotions
Siblings
Dopamine
Brain
Brain Diseases
Amygdala
Prefrontal Cortex
Healthy Volunteers
Magnetic Resonance Imaging
Phenotype
Enzymes
Genes

Keywords

  • COMT
  • emotion processing
  • genetic vulnerability
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology

Cite this

Interaction between catechol-O-methyltransferase (COMT) Val 158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli. / Lo Bianco, L.; Blasi, G.; Taurisano, P.; Di Giorgio, A.; Ferrante, F.; Ursini, G.; Fazio, L.; Gelao, B.; Romano, R.; Papazacharias, A.; Caforio, G.; Sinibaldi, L.; Popolizio, T.; Bellantuono, C.; Bertolino, A.

In: Psychological Medicine, Vol. 43, No. 2, 02.2013, p. 279-292.

Research output: Contribution to journalArticle

Lo Bianco, L, Blasi, G, Taurisano, P, Di Giorgio, A, Ferrante, F, Ursini, G, Fazio, L, Gelao, B, Romano, R, Papazacharias, A, Caforio, G, Sinibaldi, L, Popolizio, T, Bellantuono, C & Bertolino, A 2013, 'Interaction between catechol-O-methyltransferase (COMT) Val 158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli', Psychological Medicine, vol. 43, no. 2, pp. 279-292. https://doi.org/10.1017/S0033291712001134
Lo Bianco, L. ; Blasi, G. ; Taurisano, P. ; Di Giorgio, A. ; Ferrante, F. ; Ursini, G. ; Fazio, L. ; Gelao, B. ; Romano, R. ; Papazacharias, A. ; Caforio, G. ; Sinibaldi, L. ; Popolizio, T. ; Bellantuono, C. ; Bertolino, A. / Interaction between catechol-O-methyltransferase (COMT) Val 158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli. In: Psychological Medicine. 2013 ; Vol. 43, No. 2. pp. 279-292.
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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. Method 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.",
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AU - Di Giorgio, A.

AU - Ferrante, F.

AU - Ursini, G.

AU - Fazio, L.

AU - Gelao, B.

AU - Romano, R.

AU - Papazacharias, A.

AU - Caforio, G.

AU - Sinibaldi, L.

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N2 - 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. Method 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.

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