Association of altered CuZn superoxide dismutase and cognitive impairment in schizophrenia patients with tardive dyskinesia

• Schizophrenia patients with TD had lower CuZnSOD activity than those without TD.
• Oxidative stress in TD patients was confirmed by additional markers in a subgroup.
• Patients with TD experienced greater cognitive impairment than those without TD.
• CuZnSOD was negatively associated with attention index in either TD or non-TD group.
• Oxidative stress may contribute to both TD development and cognitive impairment.

Free radical-mediated abnormalities may contribute to the development of tardive dyskinesia (TD) and specific aspects of schizophrenia symptomatology such as cognitive deficits. Superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, was found to be abnormal in TD. While most of previous studies focused on the manganese isoform located in mitochondria, this study investigated the activities of isoform CuZnSOD present in the plasma. We recruited 113 male chronic patients with TD (n = 43) and without TD (n = 70) meeting DSM-IV criteria for schizophrenia, and 84 male control subjects. We examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), CuZnSOD activity for both the patient and control groups along with total antioxidant status (TAS) and malondialdehyde (MDA) levels in a subset of the cohort. Positive and Negative Symptom Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were assessed in the patient group. Our results showed lower CuZnSOD activity and TAS levels, but higher MDA levels in patients with TD than those without TD (all p < 0.05). Patients with TD had lower RBANS subscales of Visuospatial/Constructional (p < 0.05) and attention (p < 0.01) than those without TD. Multiple regression analysis showed that in either TD or non-TD group, CuZnSOD was an independent contributor to the attention index of RBANS (both p < 0.05). These results implicated that TD patients suffered greater oxidative stress and cognitive dysfunction than non-TD patients. Oxidative stress could contribute to both TD development and cognitive impairment.