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The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis

Published online by Cambridge University Press:  02 July 2009

A. Dutt*
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
C. McDonald
Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Republic of Ireland
E. Dempster
MRC, Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK
D. Prata
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Shaikh
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
I. Williams
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
K. Schulze
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
N. Marshall
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Walshe
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Allin
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
D. Collier
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
R. Murray
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
E. Bramon
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
*Address for correspondence: A. Dutt, MRCPsych, Division of Psychological Medicine and Psychiatry P063, Institute of Psychiatry, King's College London, De Crespigny Park, LondonSE5 8AF, UK. (Email:



Morphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis.


A total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family.


The results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes.


Abnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.

Original Articles
Copyright © Cambridge University Press 2009

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The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis
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