title: Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis--Preliminary fMRI findings.
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.
authors.affiliation: Department of Psychiatry, Helsinki University and Helsinki University Central Hospital, Välskärinkatu 12, P.O Box 590, 00029 HUS, Finland; Department of Neuroscience and Biomedical engineering and Advanced Magnetic Imaging Centre, Aalto NeuroImaging, Aalto University School of Science, P.O Box 13000, 00076 AALTO, Finland. Electronic address: raijtu@neuro.hut.fi.
authors.forename: Tuukka T
authors.initials: TT
authors.lastname: Raij
authors.affiliation: Department of Neuroscience and Biomedical engineering and Advanced Magnetic Imaging Centre, Aalto NeuroImaging, Aalto University School of Science, P.O Box 13000, 00076 AALTO, Finland; Department of Health, Mental Health Unit, National Institute for Health and Welfare, Helsinki, P.O. Box 30, 00271 Helsinki, Finland; Institute of Behavioural Sciences, Siltavuorenpenger 1-5, P.O. Box 9, 00014 University of Helsinki, Helsinki, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Mäntylä
authors.affiliation: Department of Psychiatry, Helsinki University and Helsinki University Central Hospital, Välskärinkatu 12, P.O Box 590, 00029 HUS, Finland; Department of Health, Mental Health Unit, National Institute for Health and Welfare, Helsinki, P.O. Box 30, 00271 Helsinki, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Kieseppä
authors.affiliation: Department of Health, Mental Health Unit, National Institute for Health and Welfare, Helsinki, P.O. Box 30, 00271 Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Suvisaari
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D016022:Case-Control Studies; D003702:Delusions / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005387:Finland; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D011699:Putamen / Q000187:drug effects* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotics; Default mode network; Delusion; Functional magnetic resonance imaging; Medial temporal lobe; Psychosis; Salience network; Striatum