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Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli

Published online by Cambridge University Press:  23 May 2012

L. Lo Bianco ,
G. Blasi ,
P. Taurisano ,
A. Di Giorgio ,
F. Ferrante ,
G. Ursini ,
L. Fazio ,
B. Gelao ,
R. Romano  and
A. Papazacharias
...Show all authors
L. Lo Bianco
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy Psychiatric Unit, Department of Mental Health, United Hospitals of Ancona, Polytechnic University of Marche, Italy
G. Blasi
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
P. Taurisano
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
A. Di Giorgio
Affiliation:
Psychiatric Liaison Service, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy
F. Ferrante
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
G. Ursini
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
L. Fazio
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
B. Gelao
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
R. Romano
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
A. Papazacharias
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
G. Caforio
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
L. Sinibaldi
Affiliation:
Mendel Lab, IRCSS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy
T. Popolizio
Affiliation:
Section of Neuroradiology, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy
C. Bellantuono
Affiliation:
Psychiatric Unit, Department of Mental Health, United Hospitals of Ancona, Polytechnic University of Marche, Italy
A. Bertolino*
Affiliation:
Psychiatric Neuroscience Group, Department of Psychiatry and Neurology, University of Bari, Italy
*
*Address for correspondence: A. Bertolino, Ph.D., Dipartimento di Scienze Neurologiche e Psichiatriche, Università degli Studi di Bari, Piazza Giulio Cesare, 11, 70124, Bari, Italy. (Email: a.bertolino@psichiat.uniba.it)
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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.

Keywords

COMTemotion processinggenetic vulnerabilityschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 2 , February 2013 , pp. 279 - 292
Copyright
Copyright © Cambridge University Press 2012

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