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

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

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
Pages (from-to)	126-36
Number of pages	11
Journal	Biological Psychology
Volume	79
Issue number	1
DOIs	https://doi.org/10.1016/j.biopsycho.2008.03.001
Publication status	Published - Sep 2008

Keywords

Adult
Alcoholism
Alleles
Catechol O-Methyltransferase
Dopamine
Female
Genetic Variation
Genotype
Glutamic Acid
Hippocampus
Humans
Image Processing, Computer-Assisted
Long-Term Potentiation
Magnetic Resonance Imaging
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Psychiatric Status Rating Scales
Receptors, Metabotropic Glutamate
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

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10.1016/j.biopsycho.2008.03.001

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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",

year = "2008",

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doi = "10.1016/j.biopsycho.2008.03.001",

language = "English",

volume = "79",

pages = "126--36",

journal = "Biological Psychology",

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T1 - Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients

AU - Puls, I

AU - Mohr, J

AU - Wrase, J

AU - Priller, J

AU - Behr, J

AU - Kitzrow, W

AU - Makris, N

AU - Breiter, H C

AU - Obermayer, K

AU - Heinz, A

PY - 2008/9

Y1 - 2008/9

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.

KW - Adult

KW - Alcoholism

KW - Alleles

KW - Catechol O-Methyltransferase

KW - Dopamine

KW - Female

KW - Genetic Variation

KW - Genotype

KW - Glutamic Acid

KW - Hippocampus

KW - Humans

KW - Image Processing, Computer-Assisted

KW - Long-Term Potentiation

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Psychiatric Status Rating Scales

KW - Receptors, Metabotropic Glutamate

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1016/j.biopsycho.2008.03.001

DO - 10.1016/j.biopsycho.2008.03.001

M3 - Article

C2 - 18423838

VL - 79

SP - 126

EP - 136

JO - Biological Psychology

JF - Biological Psychology

SN - 0301-0511

IS - 1

ER -

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

Abstract

Keywords

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