Psychiatry Investig.  2022 Jul;19(7):570-579. 10.30773/pi.2022.0033.

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

Affiliations
  • 1Department of Psychiatry, Korea University Ansan Hospital, Ansan, Republic of Korea
  • 2Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
  • 3Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
  • 4Department of Psychology, Gachon University, Seongnam, Republic of Korea
  • 5Psychiatric Imaging, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
  • 6Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
  • 7Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
  • 8Department of Brain & Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea

Abstract


Objective
Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore 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).
Methods
Twenty-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 correlation coefficients.
Results
Non-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).
Conclusion
Our findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal 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.

Keyword

Schizophrenia; Treatment-resistant; Dopamine; PET; Diffusion tensor imaging
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