1. ¹Laboratory for Psychophysiology and Functional Imaging, Department of Psychiatry, University of Würzburg, Würzburg, Bavaria, Germany
2. ²Department of Psychiatry, University of Münster, Münster, Germany
3. ³Department of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg (Saar), Germany

Correspondence: Dr AJ Fallgatter, Laboratory for Psychophysiology and Functional Imaging, Department of Psychiatry and Psychotherapy, University of Wuerzburg, Füchsleinstr. 15, Würzburg, Bavaria 97080, Germany. Tel: +49 931 201 77100, Fax: +49 931 201 77550; E-mail: Fallgatter_A@klinik.uni-wuerzburg.de

Received 3 May 2005; Revised 20 September 2005; Accepted 2 November 2005; Published online 11 January 2006.

Abstract

DTNBP1 (dysbindin) is one of the several putative schizophrenia genes supported by association, neuroanatomical, and cellular studies. These suggest an involvement of DTNBP1 in the prefrontal cortex and cognitive functions mediated by interaction with neurotransmitter systems, in particular glutamate. The influence of DTNBP1 gene variation on prefrontal brain function at the systemic neurophysiological level, though, has not been characterized. The NoGo-anteriorization (NGA) as an event-related potential (ERP) measure elicited during the continuous performance test (CPT) has been established as a valid neurophysiological parameter for prefrontal brain function in healthy individuals and patients with schizophrenias. In the present study, we therefore investigated the influence of eight dysbindin gene variants on the NGA as a marker of prefrontal brain function in 48 healthy individuals. Two DTNBP1 polymorphisms previously linked to schizophrenia (P1765 and P1320) were found associated with changes in the NGA. Post hoc analysis showing an influence of genetic variation at these loci on the Go centroid and frontal amplitudes suggest that this might be due to modification of the execution of motor processes by the prefrontal cortex. This is the first report on a role of DTNBP1 gene variation for prefrontal brain function at a systemic neurophysiological level in healthy humans. Future studies will have to address the relevance of this observation for patients with schizophrenias.