Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function

Pauli, Andreina; Prata, Diana P.; Mechelli, Andrea; Picchioni, Marco; Fu, Cynthia H.Y.; Chaddock, Christopher A.; Kane, Fergus; Kalidindi, Sridevi; McDonald, Colm; Kravariti, Eugenia; Toulopoulou, Timothea; Bramon, Elvira; Walshe, Muriel; Ehlert, Natascha; Georgiades, Anna; Murray, Robin; Collier, David A.; McGuire, Philip (2013). Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function. Human brain mapping, 34(9), pp. 2244-2258. Wiley-Blackwell 10.1002/hbm.22061

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Psychiatric Neurophysiology (discontinued)

UniBE Contributor:

Pauli, Andreina

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1065-9471

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Daniela Zurkinden

Date Deposited:

09 Apr 2014 11:45

Last Modified:

09 Apr 2014 11:45

Publisher DOI:

10.1002/hbm.22061

PubMed ID:

22438288

URI:

https://boris.unibe.ch/id/eprint/46022

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