Increased Striatal and Reduced Prefrontal Cerebral Blood Flow in Clinical High Risk for Psychosis

Increased striatal dopaminergic activity and decreased prefrontal functioning have been reported in individuals at clinical high risk (CHR) for psychosis. Abnormal metabolic rate might affect resting-state cerebral blood flow (rCBF) in the respective regions. Here, we examined if striatal and prefrontal rCBF differ between patients with CHR, first-episode psychosis (FEP), chronic schizophrenia-spectrum disorder (SZ) and controls. Two cohorts with a total of 122 participants were included and analyzed separately: 32 patients with SZ and 31 healthy controls (HC) from the University Hospital of Psychiatry, and 59 patients from the Bern Early Recognition and Intervention Center (29 with CHR, 12 with FEP, and 18 clinical controls [CC]). Ultra-high risk criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes, basic symptom criteria with the Schizophrenia Proneness Instrument. rCBF was measured with pseudo-continuous arterial spin labeling 3T-Magnetic Resonance Imaging. Striatal rCBF was significantly increased and prefrontal rCBF significantly decreased in the SZ group compared to HC group and in the CHR and FEP groups compared to CC group. Striatal rCBF correlated significantly with positive symptom scores in SZ and CHR. An inverse correlation between striatal and frontal rCBF was found in controls (HC, CC), but not in patient groups (SZ, FEP, CHR). This is the first study to demonstrate increased neuronal activity within the striatum, but reduced prefrontal activity in patients with CHR, FEP, and SZ compared to the respective controls. Our results indicate that alterations in striatal and prefrontal rCBF are reflecting metabolic abnormalities preceding the onset of frank psychosis.