Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients

I. Puls; J. Mohr; J. Wrase; J. Priller; J. Behr; W. Kitzrow; N. Makris; H. C. Breiter; K. Obermayer; A. Heinz

doi:10.1016/j.biopsycho.2008.03.001

Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients

I. Puls, J. Mohr, J. Wrase, J. Priller, J. Behr, W. Kitzrow, N. Makris, H. C. Breiter, K. Obermayer, A. Heinz^*

^*Corresponding author for this work

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Several genes of the dopaminergic and glutamatergic neurotransmitter systems have been found to be associated with alcohol disease and related intermediate phenotypes. Here, we evaluated genetic variants of the catechol-O-methyltransferase (COMT) and the metabotropic glutamate receptor 3 (mGluR3) genes in alcohol-dependent patients and their association with volumetric measurements of brain structures. By combined analysis of imaging data and genotyping results, large numbers of variables are produced that overstrain conventional statistical methods based on tests for group differences. Limitations in assessment of epistatic effects and multiple testing problems are encountered. Therefore, we introduce a novel method for detecting associations between a set of genetic markers and phenotypical measurements based on machine learning techniques. Hippocampal volume was found to be associated with epistatic effects of the COMT-mGluR3 genes in alcohol-dependent patients but not in controls. These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease.

Original language	English (US)
Pages (from-to)	126-136
Number of pages	11
Journal	Biological Psychology
Volume	79
Issue number	1
DOIs	https://doi.org/10.1016/j.biopsycho.2008.03.001
State	Published - Sep 2008

Funding

We are grateful to all patients and control subjects for their study participation. We also thank Anne Beck for assistance with the figure design. This work was funded by the Bernstein Center for Computational Neuroscience Berlin (BMBF grant 01GQ0411) and the Deutsche Forschungsgemeinschaft (He 2597-4-3). Quantitative phenotype information from the MGH Phenotype–Genotype Project was supported by a grant (DABK39-03-C-0098) from the Office of National Drug Control Policy, Counterdrug Technology Assessment Center (ONDCP-CTAC), Washington, DC.

Keywords

Alcohol addiction
COMT
Dopamine
Glutamate
Hippocampal volume
Machine learning
P-SVM
Variable selection
mGluR3

ASJC Scopus subject areas

Neuropsychology and Physiological Psychology
General Neuroscience

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10.1016/j.biopsycho.2008.03.001

Cite this

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title = "Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients",

abstract = "Several genes of the dopaminergic and glutamatergic neurotransmitter systems have been found to be associated with alcohol disease and related intermediate phenotypes. Here, we evaluated genetic variants of the catechol-O-methyltransferase (COMT) and the metabotropic glutamate receptor 3 (mGluR3) genes in alcohol-dependent patients and their association with volumetric measurements of brain structures. By combined analysis of imaging data and genotyping results, large numbers of variables are produced that overstrain conventional statistical methods based on tests for group differences. Limitations in assessment of epistatic effects and multiple testing problems are encountered. Therefore, we introduce a novel method for detecting associations between a set of genetic markers and phenotypical measurements based on machine learning techniques. Hippocampal volume was found to be associated with epistatic effects of the COMT-mGluR3 genes in alcohol-dependent patients but not in controls. These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease.",

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author = "I. Puls and J. Mohr and J. Wrase and J. Priller and J. Behr and W. Kitzrow and N. Makris and Breiter, {H. C.} and K. Obermayer and A. Heinz",

note = "Funding Information: We are grateful to all patients and control subjects for their study participation. We also thank Anne Beck for assistance with the figure design. This work was funded by the Bernstein Center for Computational Neuroscience Berlin (BMBF grant 01GQ0411) and the Deutsche Forschungsgemeinschaft (He 2597-4-3). Quantitative phenotype information from the MGH Phenotype–Genotype Project was supported by a grant (DABK39-03-C-0098) from the Office of National Drug Control Policy, Counterdrug Technology Assessment Center (ONDCP-CTAC), Washington, DC. ",

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AU - Priller, J.

AU - Behr, J.

AU - Kitzrow, W.

AU - Makris, N.

AU - Breiter, H. C.

AU - Obermayer, K.

AU - Heinz, A.

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N2 - Several genes of the dopaminergic and glutamatergic neurotransmitter systems have been found to be associated with alcohol disease and related intermediate phenotypes. Here, we evaluated genetic variants of the catechol-O-methyltransferase (COMT) and the metabotropic glutamate receptor 3 (mGluR3) genes in alcohol-dependent patients and their association with volumetric measurements of brain structures. By combined analysis of imaging data and genotyping results, large numbers of variables are produced that overstrain conventional statistical methods based on tests for group differences. Limitations in assessment of epistatic effects and multiple testing problems are encountered. Therefore, we introduce a novel method for detecting associations between a set of genetic markers and phenotypical measurements based on machine learning techniques. Hippocampal volume was found to be associated with epistatic effects of the COMT-mGluR3 genes in alcohol-dependent patients but not in controls. These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease.

AB - Several genes of the dopaminergic and glutamatergic neurotransmitter systems have been found to be associated with alcohol disease and related intermediate phenotypes. Here, we evaluated genetic variants of the catechol-O-methyltransferase (COMT) and the metabotropic glutamate receptor 3 (mGluR3) genes in alcohol-dependent patients and their association with volumetric measurements of brain structures. By combined analysis of imaging data and genotyping results, large numbers of variables are produced that overstrain conventional statistical methods based on tests for group differences. Limitations in assessment of epistatic effects and multiple testing problems are encountered. Therefore, we introduce a novel method for detecting associations between a set of genetic markers and phenotypical measurements based on machine learning techniques. Hippocampal volume was found to be associated with epistatic effects of the COMT-mGluR3 genes in alcohol-dependent patients but not in controls. These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease.

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Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients

Abstract

Funding

Keywords

ASJC Scopus subject areas

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