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Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome

Published online by Cambridge University Press:  10 May 2007

T. van Amelsvoort ,
J. Zinkstok ,
M. Figee ,
E. Daly ,
R. Morris ,
M. J. Owen ,
K. C. Murphy ,
L. De Haan ,
D. H. Linszen  and
B. Glaser
...Show all authors
T. van Amelsvoort*
Affiliation:
Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands
J. Zinkstok
Affiliation:
Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands
M. Figee
Affiliation:
Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands
E. Daly
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
R. Morris
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
M. J. Owen
Affiliation:
Department of Psychological Medicine, Cardiff University, Cardiff, UK
K. C. Murphy
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
L. De Haan
Affiliation:
Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands
D. H. Linszen
Affiliation:
Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands
B. Glaser
Affiliation:
Department of Psychological Medicine, Cardiff University, Cardiff, UK
D. G. M. Murphy
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
*
*Address for correspondence: T. van Amelsvoort, M.D., Department of Psychiatry, Academic Medical Centre, Tafelbergweg 25, 1105 BC, Amsterdam, The Netherlands. (Email: [email protected])
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Abstract

Background

Velo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (Val158Met) affecting enzyme activity. Here, we investigated the effect of COMT Val158Met polymorphism on brain anatomy and cognition in adults with VCFS.

Method

The COMT Val158Met polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery.

Results

After corrections for multiple comparisons Val-hemizygous subjects, compared with Met-hemizygotes, had a significantly larger volume of frontal lobes. Also, Val-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found.

Conclusions

COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.

Keywords

COMTVCFS22q11MRIcognition
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 1 , January 2008 , pp. 89 - 100
Copyright
Copyright © Cambridge University Press 2007

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