The Relationship Between Frontostriatal Connectivity and Striatal Dopamine Function in Schizophrenia: An18F-DOPA PET and Diffusion Tensor Imaging Study in Treatment Responsive and Resistant Patients

Sangho Shin, Wi Hoon Jung, Robert McCutcheon, Mattia Veronese, Katherine Beck, Jae Sung Lee, Yun Sang Lee, Oliver D. Howes, Euitae Kim*, Jun Soo Kwon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
30 Downloads (Pure)

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 Ki cer) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between Ki cer 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. Psychiatry Investig 2022;19(7):570-579.

Original languageEnglish
Pages (from-to)570-579
Number of pages10
JournalPsychiatry Investigation
Volume19
Issue number7
DOIs
Publication statusPublished - 21 Jul 2022

Keywords

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

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