title: Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function.
abstract: The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom. andreina.pauli@kcl.ac.uk
authors.forename: Andreina
authors.initials: A
authors.lastname: Pauli
authors.forename: Diana P
authors.initials: DP
authors.lastname: Prata
authors.forename: Andrea
authors.initials: A
authors.lastname: Mechelli
authors.forename: Marco
authors.initials: M
authors.lastname: Picchioni
authors.forename: Cynthia H Y
authors.initials: CH
authors.lastname: Fu
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Chaddock
authors.forename: Fergus
authors.initials: F
authors.lastname: Kane
authors.forename: Sridevi
authors.initials: S
authors.lastname: Kalidindi
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kravariti
authors.forename: Timothea
authors.initials: T
authors.lastname: Toulopoulou
authors.forename: Elvira
authors.initials: E
authors.lastname: Bramon
authors.forename: Muriel
authors.initials: M
authors.lastname: Walshe
authors.forename: Natascha
authors.initials: N
authors.lastname: Ehlert
authors.forename: Anna
authors.initials: A
authors.lastname: Georgiades
authors.forename: Robin
authors.initials: R
authors.lastname: Murray
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002352:Carrier Proteins / Q000235:genetics*; D004298:Dopamine / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004843:Epistasis, Genetic / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D047908:Intracellular Signaling Peptides and Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics; D014706:Verbal Learning
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018698:Glutamic Acid; D004298:Dopamine