Project Details
Projekt
Striatal dopamine in psychosis and psychotic remission and its relevance for cognitive difficulties in schizophrenia: a longitudinal 18FDOPA PET/fMRI hybrid imaging study
Subject Area
Biological Psychiatry
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 491096247
This proposal is about the longitudinal assessment of patients with schizophrenia and healthy controls with simultaneous 18F-DOPA-PET and resting-state functional MRI. It addresses four questions: (i) Is striatal aberrant dopamine synthesis capacity (DSC) course-sensitive in schizophrenia, i.e., increased during psychosis and decreased during psychotic remission? (ii) Does the course of aberrant striatal DSC link with patients’ cognitive difficulties? (iii) Is this relationship mediated by specific patterns of aberrant functional connectivity of ongoing brain activity in patients? (iv) Does simultaneous PET/MRI have the potential to improve PET-based DSC measurement? Ad (i): Previous PET studies have consistently reported that dopamine transmission in the striatum is increased in patients with schizophrenia. The most robust finding is increased DSC in the dorsal striatum during psychosis. However, recent evidence has indicated that such elevation is not present during phases of psychotic remission. However, it remains unclear whether striatal DSC changes are caused by disorder course (i.e., psychotic episodes vs. phases of psychotic remission) or rather by antipsychotic medication. To address this issue, we propose a longitudinal study in which striatal DSC will be measured by 18F-DOPA-PET twice within the same group of patients with schizophrenia – once during psychosis and once after remission of psychosis – and healthy control subjects. To investigate potential medium-term dose-dependent effects of antipsychotic medication, we will include patients both without and with antipsychotic medication in variable doses.Ad (ii): Additionally, we plan to use this experimental design to investigate the relationship between altered striatal DSC and cognitive difficulties in patients with schizophrenia (e.g., impaired cognitive flexibility). Based on previous cross-sectional evidence in patients, we expect an inverted U-shaped association between cognitive flexibility and striatal DSC: both elevated and decreased DSC lead to impaired cognitive flexibility, with optimal cognitive function at some ‘intermediate’ DSC. Ad (iii): Focusing on simultaneously assessed blood oxygenation level-dependent (BOLD) signals – a proxy for neural activity – in the whole brain, we plan to study whether specific patterns of intrinsic functional connectivity of ongoing BOLD fluctuations mediate effects of altered striatal DSC both on cognitive and psychotic symptoms. As mediators we expect impaired intrinsic functional connectivity between distinct cortical networks and thalamus.Ad (iv): Finally, we intend to use the simultaneous acquisition of PET and MRI data to improve 18F-DOPA-PET-based DSC measurement. Specifically, we plan to improve the physiological definition of our DSC metric (kicer) by using an image-derived arterial input function (IDAIF) based on perfusion MRI for absolute quantitation of tracer uptake.
DFG Programme
Research Grants
Co-Investigators
Professor Dr. Stefan Leucht; Professorin Dr. Sibylle Ilse Ziegler
