>Background: Dysbindin, encoded by risk factor gene DTNBP1, is downregulated in cortex and hippocampus of schizophrenia subjects and modulates copper (required for monoamine metabolism and myelination). >Methods: The current study used Western blot analysis to compare protein levels of copper transporters ATP7A and CTR1, and dysbindin in postmortem substantia nigra in schizophrenia subjects (n = 15) and matched controls (n = 12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off- (n = 4) or on-medication (n = 11) or (2) treatment response: treatment resistant (n = 6) or treatment responsive (n = 4). >Results: The combined schizophrenia group exhibited decreased CTR1 levels (a decrease of 42.6%, P = .0003) versus controls. When subdivided by medication status, this decrease was observed in medicated (a decrease of 39.5%, P = .007) and unmedicated subjects (a decrease of 52.9%, P = .001) versus controls. ATP7A levels were decreased in unmedicated subjects versus medicated subjects (a decrease of 38.3%, P = .007) and controls (a decrease of 35.3%, P = .017). Decreased CTR1 levels were also observed in responsive schizophrenia subjects versus controls (a decrease of 47.1%, P = .007) when subdivided by treatment response. Protein levels of dysbindin were not significantly different for any of the analyses. Correlational analyses and comparison of correlation coefficients revealed no significant relationships between CTR1 and dysbindin in any group. However, a positive relationship between ATP7A and dysbindin was observed in unmedicated subjects (r = .997, P = .003) that was significantly different from medicated subjects (r = −.190, P = .575, CC: P = .007) and controls (r = .180, P = .557, CC: P = .003). >Conclusion: These results indicate disrupted nigral copper homeostasis in schizophrenia subjects that is partially rescued by antipsychotic treatment. Genetic variation and region-specific protein expression of DTNBP1 may be related but require further analysis.
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