Striatal dopamine synthesis in schizophrenia decreases from psychosis to psychotic remission

Schizophrenia frequently follows a chronic relapsing-remitting course, comprising alternating episodes with and without psychotic symptoms (hereafter: psychosis and psychotic remission). One potential neurobiological correlate of this course is aberrant dopamine synthesis and storage (DSS) in the striatum, which can be estimated by the 18F-DOPA positron emission tomography (PET) outcome kicer. We conducted a longitudinal study of state-related kicer changes in striatal subregions in medicated patients with multiple-episode schizophrenia. We hypothesised that striatal DSS in patients with schizophrenia decreases from psychosis to psychotic remission, with higher striatal DSS during psychosis and lower striatal DSS during psychotic remission, compared to healthy subjects. Additionally, we explored whether striatal DSS is associated with psychotic relapse after remission. 18F-DOPA PET scans and clinical assessments were conducted in 28 patients with schizophrenia at two timepoints, first during psychosis and second during early-to-moderate psychotic remission (6 weeks to 12 months after the first timepoint, 189±80 days between-scan interval), as well as in 21 healthy controls, assessed twice in a comparable time interval. The averaged influx constant kicer of the striatal subregions nucleus accumbens, caudate and putamen was calculated as a proxy for DSS, using voxel-wise Gjedde-Patlak modelling with a cerebellar reference region. Mixed-effects models and post hoc analyses were used to test for longitudinal changes in kicer and cross-sectional group differences. An exploratory clinical follow-up 12 months after the second scan was conducted to assess psychotic relapse, and post hoc ANCOVAs were used to test for differences in kicer at each session between relapsing and non-relapsing patients. Patients' kicer changes from psychosis to psychotic remission in caudate and nucleus accumbens differed significantly from assessments in healthy controls at comparable time points, with a significant longitudinal decrease of caudate kicer in patients. Furthermore, kicer in both caudate and accumbens was significantly lower in patients during early-to-moderate psychotic remission compared to controls, but no significant group difference was observed during psychosis. At the exploratory clinical follow-up, 32% of patients had experienced a psychotic relapse; they showed higher caudate kicer compared to non-relapsing patients during psychosis, with no difference during psychotic remission. These findings provide evidence for longitudinal changes of striatal, particularly caudate, DSS from psychosis to psychotic remission in medicated, multiple-episode schizophrenia patients, with lower caudate DSS during early-to-moderate psychotic remission but no aberrance during psychosis. The data indicate aberrant, fluctuating striatal dopamine synthesis across disorder states in schizophrenia.