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: Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent. METHOD: Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons. RESULTS: At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophrenia patients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r=-0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018). CONCLUSIONS: White matter deficits were validated in the present study by a relatively large sample of medication naive and first episode schizophrenia patients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies.