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Effects of the DAT 3’UTR VNTR Genotype on Brain Function in Healthy Subjects and Patients with Schizophrenia

Published online by Cambridge University Press:  16 April 2020

D.P. Prata
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
A. Mechelli
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
C. Fu
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
M. Picchioni
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
F. Kane
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
S. Kalidindi
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
C. Mcdonald
Affiliation:
Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Ireland
E. Kravariti
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
T. Toulopoulou
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
F. Saeedzadeh-Sardahaee
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
R. Murray
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
D. Collier
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK
P. Mcguire
Affiliation:
Psychological Medicine, Institute of Psychiatry, London, UK

Abstract

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Aims:

To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:

  1. 1. determine the extent to which this is altered in schizophrenia and

  2. 2. use a verbal fluency paradigm.

This is relevant since:

  1. 1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and

  2. 2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.

Method:

Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.

Results:

The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.

Conclusion:

Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.

Type
P02-09
Copyright
Copyright © European Psychiatric Association 2009
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