Altered reward functions in patients on atypical antipsychotic medication in line with the revised dopamine hypothesis of schizophrenia

• Published in: Psychopharmacologia Vol. 206; no. 1; pp. 121 - 132
• Main Authors: Walter, Henrik, Kammerer, Hannes, Frasch, Karel, Spitzer, Manfred, Abler, Birgit
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.09.2009; Springer; Springer Nature B.V
• Subjects: Adult; Adult and adolescent clinical studies; Antipsychotic Agents - pharmacology; Antipsychotic Agents - therapeutic use; Basal Ganglia - physiopathology; Benzodiazepines - pharmacology; Benzodiazepines - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain; Dopamine - metabolism; Female; Gyrus Cinguli - physiopathology; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Neuropharmacology; Neurosciences; Neurotransmitters; NMR; Nuclear magnetic resonance; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Prefrontal Cortex - physiopathology; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Psychotropic drugs; Reward; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - physiopathology; Schizophrenic Psychology; Schizophrenia; fMRI; Dopamine; Positive and negative symptoms; Reward; Atypical antipsychotic; Olanzapine; Neuroleptic; Psychotropic; Serotonine receptor; Psychosis; Negative symptom; Mesolimbic pathway; Antagonist; Positive symptom; FMRI; Human; Drug; Dopamine antagonist; Serotonin antagonist; Exploration; Catecholamine; Nuclear magnetic resonance imaging; Thienobenzodiazepine derivatives; Symptomatology; D2 Dopamine receptor; Neurotransmitter; Comparative study; Functional imaging
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-009-1586-4

Objective To study the mesolimbic dopamine system during expectation and receipt or omission of rewards in partially remitted patients with schizophrenia treated with the atypical antipsychotic olanzapine. Methods We studied 16 patients with a current episode of schizophrenia, all treated with the atypical drug olanzapine, and 16 healthy subjects using functional magnetic resonance imaging. Subjects performed a delayed incentive paradigm with monetary rewards. Results During reward expectation, both, patients with schizophrenia and healthy control subjects, showed activation of the ventral striatum and midbrain in the vicinity of the ventral tegmental area. Significant categorical group differences emerged in the anterior cingulate cortex with only healthy controls showing increasing activation with increasing reward. In the patients, activation of this region was inversely correlated with positive symptoms. During outcome, both, patients with schizophrenia and healthy controls, showed activation of the ventral striatum and the mesial prefrontal cortex. Significant categorical group differences emerged in the right ventrolateral prefrontal cortex for the salience contrast with healthy controls showing a U-shaped activation curve, i.e., higher activation for either omission or receipt of reward compared to no reward. Conclusions Our findings partially support the current concept of dopaminergic dysfunction in schizophrenia, suggesting a rather hyperactive mesolimbic dopamine system and reduced prefrontal activation, at least in partially remitted patients treated with atypical antipsychotics.