The Relationship Between Frontostriatal Connectivity and Striatal Dopamine Function in Schizophrenia: An 18F-DOPA PET and Diffusion Tensor Imaging Study in Treatment Responsive and Resistant Patients

Abstract

ObjectiveStriatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefron-tal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connec-tivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We there-fore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC). MethodsTwenty-four patients with schizophrenia and twelve HC underwent [18F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant Kicer) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between Kicer and FA in each group were evaluated using Spearman's rho cor-relation coefficients. ResultsNon-TRS showed a negative correlation (r=-0.629, p=0.028) between connectivity of dorsolateral prefrontal cortex-associative striatum (DLPFC-AST) and dopamine synthesis capacity of associative striatum but this was not evident in TRS (r=-0.07, p=0.829) and HC (r=-0.277, p=0.384). ConclusionOur findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to pre-frontal cortex pathology localized to connectivity of DLPFC-AST in non-TRS, and also extend the hypothesis to suggest that different mechanisms underlie the pathophysiology of non-TRS and TRS.