Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis-Preliminary fMRI findings.

Psychiatry Res. 2015 Jun 30;

Authors: Raij TT, Mäntylä T, Kieseppä T, Suvisaari J

Abstract
The dopamine theory proposes the relationship of delusions to aberrant signaling in striatal circuitries that can be normalized with dopamine D2 receptor-blocking drugs. Localization of such circuitries, as well as their upstream and downstream signaling, remains poorly known. We collected functional magnetic resonance images from first-episode psychosis patients and controls during an audiovisual movie. Final analyses included 20 patients and 20 controls; another sample of 10 patients and 10 controls was used to calculate a comparison signal-time course. We identified putamen circuitry in which the signal aberrance (poor correlation with the comparison signal time course) was predicted by the dopamine theory, being greater in patients than controls; correlating positively with delusion scores; and correlating negatively with antipsychotic-equivalent dosage. In Granger causality analysis, patients showed a compromised contribution of the cortical salience network to the putamen and compromised contribution of the putamen to the default mode network. Results were corrected for multiple comparisons at the cluster level with primary voxel-wise threshold p<0.005 for the salience network contribution, but liberal primary threshold p<0.05 was used in other group comparisons. If replicated in larger studies, these findings may help unify and extend current hypotheses on dopaminergic dysfunction, salience processing and pathogenesis of delusions.

PMID: 26184459 [PubMed - as supplied by publisher]