Background
There is growing evidence that the gene catechol-O-methyltransferase (COMT) is involved
in the etiopathogenesis of schizophrenia. This study sought to clarify the effects
of the COMT Val158Met polymorphism on brain structure, function, and risk of developing schizophrenia
in a well-characterized cohort of individuals at high risk of schizophrenia for familial
reasons.
Methods
In a sample of 78 people at high genetic risk of schizophrenia, the risk of progression
to schizophrenia associated with the COMT Val allele was estimated. The relationship
of the Val allele to brain structure and function was investigated using structural
magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI)
data collected on the high-risk subjects before their disease outcome was known.
Results
The COMT Val allele increased the risk of schizophrenia in this cohort in a dose-dependent
manner. Subjects with the COMT Val allele had reduced gray matter density in anterior
cingulate cortex. In addition, there was evidence of increased activation in lateral
prefrontal cortex and anterior and posterior cingulated, with increasing sentence
difficulty in those with the COMT Val allele despite a similar level of performance.
Conclusions
The COMT Val allele is associated with an increased risk of schizophrenia in subjects
at increased familial risk, in whom it has demonstrable effects on prefrontal brain
structure and function. These patterns of altered brain structure and function have
previously been associated with schizophrenia in this and other samples.
Key Words
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Article info
Publication history
Published online: October 04, 2006
Accepted:
May 23,
2006
Received in revised form:
May 11,
2006
Received:
March 9,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
