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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 ,
C. McDonald ,
E. Dempster ,
D. Prata ,
M. Shaikh ,
I. Williams ,
K. Schulze ,
N. Marshall ,
M. Walshe  and
M. Allin
...Show all authors
A. Dutt*
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
C. McDonald
Affiliation:
Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Republic of Ireland
E. Dempster
Affiliation:
MRC, Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK
D. Prata
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Shaikh
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
I. Williams
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
K. Schulze
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
N. Marshall
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Walshe
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Allin
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
D. Collier
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
R. Murray
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
E. Bramon
Affiliation:
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, London SE5 8AF, UK. (Email: [email protected])
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Abstract

Background

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.

Method

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.

Results

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.

Conclusions

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.

Keywords

Bipolarendophenotypesgeneshippocampusschizophreniaventricles
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 11 , November 2009 , pp. 1783 - 1797
Copyright
Copyright © Cambridge University Press 2009

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