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Prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism

Published online by Cambridge University Press:  08 February 2008

P. Roussos ,
S. G. Giakoumaki ,
M. Rogdaki ,
S. Pavlakis ,
S. Frangou  and
P. Bitsios
P. Roussos
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Crete, Heraklion, Greece
S. G. Giakoumaki
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Crete, Heraklion, Greece Section of Neurobiology of Psychosis, Institute of Psychiatry, London, UK
M. Rogdaki
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Crete, Heraklion, Greece
S. Pavlakis
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Crete, Heraklion, Greece Royal Free and University College Medical School, Department of Clinical Sciences, University College London, UK
S. Frangou
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Crete, Heraklion, Greece
P. Bitsios*
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Crete, Heraklion, Greece Section of Neurobiology of Psychosis, Institute of Psychiatry, London, UK
*
*Address for correspondence: Dr P. Bitsios, Department of Psychiatry and Behavioural Sciences, Faculty of Medicine, PO Box 2208, University of Crete, Heraklion 71003, Crete, Greece. (Email: [email protected])
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Abstract

Background

Recent evidence suggests that dopamine (DA) agonist-induced disruption of prepulse inhibition (PPI) depends on basal PPI values, in a manner that suggests an inverted U-shaped relationship between PPI and prefrontal DA levels. This is the first study to examine possible genetic determinants of PPI and the catechol O-methyltransferase (COMT) Val158Met polymorphism, the main catabolic pathway of released DA in the prefrontal cortex (PFC).

Method

PPI was measured in 93 healthy males presented with 75-dB and 85-dB prepulses at 60-ms and 120-ms prepulse–pulse intervals. Subjects were grouped according to their COMT status into a Val/Val, a Val/Met and a Met/Met group.

Results

ANOVAs showed that at all prepulse and interval conditions, Val/Val individuals had the lowest PPI, Met/Met the highest, and Val/Met were intermediate.

Conclusions

These results suggest that PPI is regulated by DA neurotransmission in the PFC and its levels depend on the COMT Val158Met gene polymorphism. These findings enhance the value of the PPI paradigm in examining individual variability of early information processing in healthy subjects and psychiatric disorders associated with changes in PFC DA activity and attentional deficits such as schizophrenia.

Keywords

COMThealthyprepulse inhibitionVal158Met polymorphism
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 11 , November 2008 , pp. 1651 - 1658
Copyright
Copyright © 2008 Cambridge University Press

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