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The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.

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Cognitive impairment is a central aspect of schizophrenia (SCZ) that occurs at the onset of the disease and is related to poor social function and outcome in patients with SCZ. Recent literatures have revealed repetitive transcranial magnetic stimulation (rTMS) to be one of the efficient medical interventions for cognitive impairments. However, no study has been conducted to investigate the treatment effectiveness of 20 Hz rTMS with neuronavigation system administered to the left dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. In this randomized, double-blind and sham-controlled study, 56 patients were enrolled in 20 Hz rTMS (n = 28) or sham stimulation (n = 28) over left DLPFC for 8 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to measure the cognitive function at baseline and after 8 weeks of rTMS treatment. The positive and negative syndrome scales (PANSS) was performed to assess the clinical symptoms at baseline, after 2-week treatment, 4-week treatment, 6-week treatment, and 8-week treatment. Totally, 15 subjects (seven in active group and eight in sham group) dropped out during the trial and the main findings were from completed 41 patients. At 2 weeks, 4 weeks, and 6 weeks, there were no significant differences in PANSS total score and subscores between the sham and treatment groups. At 8 weeks, the 20 Hz rTMS significantly increased the immediate memory score compared with the sham. Furthermore, the improvement in the immediate memory score was correlated with the decrease in the excitement factor score of the patients with SCZ. Our results suggest that 20 Hz rTMS appears to be an effective treatment for improving the cognitive performance and reducing the clinical symptoms of patients with SCZ.

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