title: Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning.
abstract: Working memory deficits are found in different psychiatric populations and are most pronounced in schizophrenia. There is preliminary evidence from pharmacological studies that the verbal and visuospatial subcomponents of working memory are subject to differential neurotransmitter modulation. Here, we investigated the impact of well-known polymorphisms of the dopamine transporter gene (SLC6A3, DAT) and the catechol-O-methyl-transferase gene (COMT) as well as the serotonin transporter gene (SLC6A4, 5-HTT) on these specific working memory subcomponents in a mixed sample of patients and healthy individuals. Twenty healthy subjects and 80 patients diagnosed with schizophrenia, bipolar I disorder, or obsessive-compulsive disorder underwent genotyping for the DAT variable number of tandem repeats (VNTR), the COMT val/met-, and the 5-HTT promoter length polymorphism (5-HTTLPR) and neuropsychological testing using a battery of well-characterized, brain circuit-specific working memory tasks. DAT genotype revealed a significant and selective effect on visuospatial working memory, while there was no effect on verbal working memory functioning. 5-HTT genotype, by contrast, exerted a significant and selective effect on verbal working memory task performance. COMT genotype did not show any influence on either working memory domain. The results of the present study provide evidence for a differential impact of genetic polymorphisms of the dopaminergic and serotonergic systems on verbal and visuospatial working memory functioning. Together with prior evidence suggesting the existence of subgroups of schizophrenia patients exhibiting isolated deficits in only one working memory domain, this finding further supports the idea of endophenotypically and pathophysiologically distinct subgroups of schizophrenia with implications for personalized therapeutic approaches.
authors.affiliation: Department of Psychiatry, Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Centre, Georg August University, Goettingen, Germany. david.zilles@med.uni-goettingen.de
authors.forename: David
authors.initials: D
authors.lastname: Zilles
authors.forename: Jobst
authors.initials: J
authors.lastname: Meyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider-Axmann
authors.forename: Savira
authors.initials: S
authors.lastname: Ekawardhani
authors.forename: Eva
authors.initials: E
authors.lastname: Gruber
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology / Q000235:genetics; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D009771:Obsessive-Compulsive Disorder / Q000150:complications / Q000235:genetics; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000150:complications / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014706:Verbal Learning / Q000502:physiology*; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase