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Effects of a CACNA1C genotype on attention networks in healthy individuals

Published online by Cambridge University Press:  16 November 2010

M. Thimm ,
T. Kircher ,
T. Kellermann ,
V. Markov ,
S. Krach ,
A. Jansen ,
K. Zerres ,
T. Eggermann ,
T. Stöcker  and
N. J. Shah
...Show all authors
M. Thimm*
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany
T. Kircher
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany
T. Kellermann
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany
V. Markov
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany
S. Krach
Affiliation:
Section of Brain Imaging, Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany
A. Jansen
Affiliation:
Section of Brain Imaging, Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany
K. Zerres
Affiliation:
Institute of Human Genetics, RWTH Aachen University, Germany
T. Eggermann
Affiliation:
Institute of Human Genetics, RWTH Aachen University, Germany
T. Stöcker
Affiliation:
Institute of Neuroscience and Medicine 4, Jülich, Germany
N. J. Shah
Affiliation:
Institute of Neuroscience and Medicine 4, Jülich, Germany
M. M. Nöthen
Affiliation:
Institute of Human Genetics, University of Bonn, Germany Department of Genomics, Life and Brain Center, University of Bonn, Germany
M. Rietschel
Affiliation:
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany
S. H. Witt
Affiliation:
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany
K. Mathiak
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany
A. Krug
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany
*
*Address for correspondence: Dr M. Thimm, Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany. (Email: mthimm@ukaachen.de)
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Abstract

Background

Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be over-represented in patients with psychosis, including schizophrenia, bipolar disorder and major depressive disorder. In these disorders, attention deficits are among the main cognitive symptoms and have been related to altered neural activity in cerebral attention networks. The particular effect of CACNA1C on neural function, such as attention networks, remains to be elucidated.

Method

The current event-related functional magnetic resonance imaging (fMRI) study investigated the effect of the CACNA1C gene on brain activity in 80 subjects while performing a scanner-adapted version of the Attention Network Test (ANT). Three domains of attention were probed simultaneously: alerting, orienting and executive control of attention.

Results

Risk allele carriers showed impaired performance in alerting and orienting in addition to reduced neural activity in the right inferior parietal lobule [Brodmann area (BA) 40] during orienting and in the medial frontal gyrus (BA 8) during executive control of attention. These areas belong to networks that have been related to impaired orienting and executive control mechanisms in neuropsychiatric disorders.

Conclusions

Our results suggest that CACNA1C plays a role in the development of specific attention deficits in psychiatric disorders by modulation of neural attention networks.

Keywords

Alertingexecutive controlfMRIgenetic imagingorientingpsychiatric disorder
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 7 , July 2011 , pp. 1551 - 1561
Copyright
Copyright © Cambridge University Press 2010

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