• Chen Zhang, Xinyu Fang, Peifen Yao, Yemeng Mao, Jun Cai, Yi Zhang, Meijuan Chen, Weixing Fan, Wei Tang, and Lisheng Song.
• Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zhangchen645@gmail.com.
• Psychoneuroendocrinology. 2017 Jul 1; 81: 138-143.

ObjectiveThere is accumulating evidence indicating that long-term treatment with second-generation antipsychotics (SGAs) results in metabolic syndrome (MetS) and cognitive impairment. This evidence suggests an intrinsic link between antipsychotic-induced MetS and cognitive dysfunction in schizophrenia patients. Olanzapine is a commonly prescribed SGA with a significantly higher MetS risk than that of most antipsychotics. In this study, we hypothesized that olanzapine-induced MetS may exacerbate cognitive dysfunction in patients with schizophrenia.MethodsA sample of 216 schizophrenia patients receiving long-term olanzapine monotherapy were divided into two groups, MetS and non-MetS, based on the diagnostic criteria of the National Cholesterol Education Program's Adult Treatment Panel III. We also recruited 72 healthy individuals for a control group. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha) were measured by an enzyme-linked immunosorbent assay for 108 patients and 47 controls.ResultsAmong the 216 schizophrenia patients receiving olanzapine monotherapy, MetS was found in 95/216 (44%). Patients with MetS had more negative symptoms, higher total scores in PANSS (Ps<0.05) and lower immediate memory, attention, delayed memory and total scores in RBANS (Ps<0.01). Stepwise multivariate linear regression analysis revealed that increased glucose was the independent risk factor for cognitive dysfunction (t=-2.57, P=0.01). Patients with MetS had significantly lower BDNF (F=6.49, P=0.012) and higher TNF-alpha (F=5.08, P=0.026) levels than those without MetS. There was a negative correlation between the BDNF and TNF-alpha levels in the patients (r=-0.196, P=0.042).ConclusionOur findings provide evidence suggesting that the metabolic adverse effects of olanzapine may aggravate cognitive dysfunction in patients with schizophrenia through an interaction between BDNF and TNF-alpha.Copyright © 2017 Elsevier Ltd. All rights reserved.

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