Interaction Between Effects of Genes Coding for Dopamine and Glutamate Transmission on Striatal and Parahippocampal Function

Overview

Journal Hum Brain Mapp

Publisher Wiley

Specialty Neurology

Date 2012 Mar 23

PMID 22438288

Citations 6

Authors

Andreina Pauli

Diana P Prata

Andrea Mechelli

Marco Picchioni

Cynthia H Y Fu

Christopher A Chaddock

Fergus Kane

Sridevi Kalidindi

Colm McDonald

Eugenia Kravariti

Timothea Toulopoulou

Elvira Bramon

Muriel Walshe

Natascha Ehlert

Anna Georgiades

Robin Murray

David A Collier

Philip McGuire

Affiliations

Soon will be listed here.

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.

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