¹National Cheng Kung University, Institute of Clinical Medicine, Tainan, Taiwan, ²Chia-Yi Branch, Taichung Veterans General Hospital, Department of Psychiatry, Chia-Yi, Taiwan, ³National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Clinical Medicine Research Center, Tainan, Taiwan, ⁴National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Department of Psychiatry, Tainan, Taiwan, ⁵National Cheng Kung University and Academia Sinica, Taiwan International Graduate Program in Interdisciplinary Neuroscience, Taipei, Taiwan, ⁶College of Medicine, National Cheng Kung University, Institute of Behavioral Medicine, Tainan, Taiwan

Background: Glutamatergic system has been proposed as a potential therapeutic mechanism for patients with treatment resistant schizophrenia (TRS) whose treatment response is poor to the dopaminergic agents. Sodium benzoate (SB) is a D-amino acid oxidase inhibitor, could be a treatment choice for schizophrenia via glutamatergic system.

Aims & Objectives: The aims of present study are to test whether SB will bring symptoms improvement and benefit effect on the cognitive function among patients with TRS, and to probe the association between the concentration of glutamate in the anterior cingulate cortex and the effect of SB treatment.

Method: A total of 18 patients with TRS were randomly assigned to 6-week treatment with SB (N = 12) or placebo (N = 6). The symptoms (PANSS) severity and cognitive function (working memory, sustained attention) were probed at the baseline, week 2, and week 6. The glutamate concentration was probed by the proton magnetic resonance spectroscopy (1H-MRS) with 1.5T scanner.

Results: Reductions on the positive (week 2: Z = 2.46, P = 0.01; week 6: Z = 2.24, P = 0.03), negative (week 2: Z = 2.16, P = 0.03), and general (week 2: Z = 2.08, P = 0.04; week 6: Z = 2.81, P = 0.01) symptoms were found at week 2 and week 6 among patients receiving SB. For patients receiving placebo, the reductions of symptoms (positive and negative) were found only at week 6. The improvement of the working memory (Week 2: Z = 2.25, P = 0.03; week 6: Z = 2.14, P = 0.03) and attention (week 2: Z = 2.05, P = 0.04; week 6: Z = 2.49, P = 0.01) was found in SB subgroup. The glutamate concertation at the baseline is positively related with the reduction of negative symptoms (r = 0.72, p = 0.04) at the week 2 among patients receiving SB.

Discussion & Conclusions: The efficacy of SB for the earlier response of schizophrenia was found. The 1H-MRS glutamate concentration might be a predictor for treating with SB for patients with TRS.