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Dopaminerge Mechanismen von Störungen des Belohnungslernens und Arbeitsgedächtnisses bei schizophrenen Patienten

Antragsteller Professor Dr. Florian Schlagenhauf, seit 10/2018
Fachliche Zuordnung Biologische Psychiatrie
Förderung Förderung von 2012 bis 2023
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 204208448
 
Erstellungsjahr 2023

Zusammenfassung der Projektergebnisse

We utilized a multimodal imaging approach to examine fundamental cognitive functions, including reward learning, belief updating, and working memory, in patients with schizophrenia versus controls. During reward learning, unmedicated schizophrenia patients exhibited diminished signaling in the ventral striatal reward prediction error (RPE) compared to controls, which correlated with increased negative symptoms. While dopamine synthesis capacity was not significantly different between groups in our sample, its levels in the associative striatum correlated with the intensity of positive symptoms in the patient group. This suggested that reward learning mechanisms are connected to negative symptoms, whereas a heightened striatal dopaminergic activity might be linked to positive symptoms. Computational modeling using Hierarchical Bayesian learning models was used to describe belief updating processes. We found that schizophrenia patients misinterpreted environmental changes, which was related to executive functioning. In an online study, we found that individuals with mild psychotic tendencies formed less accurate beliefs based on fewer past experiences. Schizophrenia patients displayed reduced working memory function and reduced DLPFC activation. The relationship between DLPFC activation and glutamate levels was contingent upon medication, with unmedicated patients revealing a positive correlation. Meta-analytic evidence suggested that glutamate levels in the DLPFC may be affected by medication status with elevated levels in drug-naïve patients, hinting at a potential compensatory response for NMDAR dysfunction. Accessible and economical markers of dopaminergic neurotransmission, such as neuromelanin-sensitive Magnetic Resonance Imaging (NMRI), displayed increased signals in psychosis spectrum patients. This may help to further investigate associations between dopaminergic dysfunction in patients and cognitive functions.

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