Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients. (22nd April 2020)

• Record Type: Journal Article
• Authors: Katthagen, Teresa; Kaminski, Jakob; Heinz, Andreas; Buchert, Ralph; Schlagenhauf, Florian
• Is Part Of: Schizophrenia bulletin. Volume 46:Number 6(2020)
• Page Start: 1535
• Page End: 1546
• Publication Date: 2020-04-22
• Subjects: psychosis -- reinforcement learning -- computational psychiatry -- PET -- reversal learning -- fMRI; Schizophrenia -- Periodicals; Schizophrenia -- Research -- Periodicals; 616.898005
• DOI: 10.1093/schbul/sbaa055
• Languages: English
• ISSNs: 0586-7614

Abstract

Abstract: Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients ( n = 19) and healthy controls ( n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Ki cer ), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Ki cer . Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Ki cer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Ki cer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Ki cer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.