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.
authors.affiliation: Department of Psychiatry and Psychotherapy, CCM, Charité University Medicine, Berlin, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Puls
authors.forename: J
authors.initials: J
authors.lastname: Mohr
authors.forename: J
authors.initials: J
authors.lastname: Wrase
authors.forename: J
authors.initials: J
authors.lastname: Priller
authors.forename: J
authors.initials: J
authors.lastname: Behr
authors.forename: W
authors.initials: W
authors.lastname: Kitzrow
authors.forename: N
authors.initials: N
authors.lastname: Makris
authors.forename: H C
authors.initials: HC
authors.lastname: Breiter
authors.forename: K
authors.initials: K
authors.lastname: Obermayer
authors.forename: A
authors.initials: A
authors.lastname: Heinz
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology*; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017774:Long-Term Potentiation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics
chemical_list: D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; D018698:Glutamic Acid; D002394:Catechol O-Methyltransferase; D004298:Dopamine