Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients. Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also studied. Results: HOMA-IR and serum levels of GSSG and NO were significantly higher in SZ patients than in healthy controls (P < 0.001), while the serum levels of SOD were significantly lower than in healthy controls (P < 0.001). HOMA-IR, GSSG and NO levels were significantly correlated to the total cognitive function scores of the patient group (r = -0.345,-0.369,-0.444, respectively, P < 0.05). But these factors were not co-related to the cognitive functions in the healthy control group. And, levels of SOD, UA were not associated with the total cognitive function scores in both the patient and the healthy control groups. NO was positively correlated with general pathological and the total score in the PANSS, and was negatively correlated with six cognitive domains (r = -0.316 to -0.553, P < 0.05). Conclusions: The levels of insulin resistance and oxidative stress are elevated, and correlated with the severity of cognitive impairment in drug-naive, first-episode SZ patients. Treatment approaches targeting on reducing insulin resistance and oxidative stress may improve cognitive function in SZ patients.

Purpose: Effective treatment options for negative symptoms and cognitive impairment in patients with schizophrenia are still to be developed. The present study was to examine potential benefits of repetitive transcranial magnetic stimulation (rTMS) to improve negative symptoms and cognition in this patient population. Methods: The study was a 4-week, randomized, double-blind sham-controlled trial. Patients with schizophrenia were treated with adjunctive 20-Hz rTMS for 4 weeks or sham condition to the left dorsolateral prefrontal cortex (DLPFC). Negative symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative symptom scale (PANSS) negative subscale at baseline and week 4. Cognitive function was measured using the MATRICS Consensus Cognitive Battery (MCCB) at the same two time points. In addition, possible moderators for rTMS treatment efficacy were explored. Results: Sixty patients (33 in the treatment group, 27 in the sham group) completed the study. There was a significant decrease in negative symptoms after 4-week rTMS treatment as measured by the SANS total score and the PANSS negative symptom subscale score. However, there was no significant improvement in cognition with rTMS treatment. Stepwise multiple linear regression analysis suggested that the baseline severity of positive symptoms may predict poorer improvement in negative symptoms at week 4. Conclusion: Twenty-Hz rTMS stimulation over left DLPFC as an adjunctive treatment might be beneficial in improving negative symptoms of schizophrenia. Future studies with a longer treatment duration and a larger sample size are needed. Clinical trial ID: NCT01940939.

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota-gut-brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naive first episode schizophrenia. Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points. Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's < 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's < 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors. Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naive, first episode schizophrenia. The clinical implications of our findings were discussed.