Abstract
Increasing evidence suggests that inflammation contributes to the etiology and progression of schizophrenia. Molecules that initiate inflammation, such as virus- and toxin-induced cytokines, are implicated in neuronal degeneration and schizophrenia-like behavior. Using therapeutic agents with anti-inflammatory or neurotrophic effects may be beneficial for treating schizophrenia. One hundred healthy controls and 95 Han Chinese patients with schizophrenia were tested in this double-blind study. Their PANSS scores, plasma interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and brain-derived neurotrophic factor (BDNF) levels were measured before and after pharmacological treatment. Pretreatment, plasma levels of IL-1β and TNF-α were significantly higher in patients with schizophrenia than in controls, but plasma BDNF levels were significantly lower. Patients were treated with the atypical antipsychotic risperidone (Risp) only or with Risp+ dextromethorphan (DM). PANSS scores and plasma IL-1β levels significantly decreased, but plasma TNF-α and BDNF levels significantly increased after 11 weeks of Risp treatment. Patients in the Risp+ DM group showed a greater and earlier reduction of symptoms than did those in the Risp-only group. Moreover, Risp+ DM treatment attenuated Risp-induced plasma increases in TNF-α. Patients with schizophrenia had a high level of peripheral inflammation and a low level of peripheral BDNF. Long-term Risp treatment attenuated inflammation and potentiated the neurotrophic function but also produced a certain degree of toxicity. Risp+ DM was more beneficial and less toxic than Risp-only treatment.
Clinical Trial Registration: Protocol Record: HR-93-50; Trial Registration number: NCT01189006; URL: http://www.clinicaltrials.gov
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Acknowledgments
This study was supported in part by the grant DOH95-TD-I-111-004 from the Taiwan Ministry of Health (to RBL), the Taiwan National Science Council NSC98-2627-B-006-017 (to RBL) and by a grant from the National Cheng Kung University Project to Promote Academic Excellence and Develop a World-Class Research Center, Taiwan.
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Chen, SL., Lee, SY., Chang, YH. et al. Inflammation in Patients with Schizophrenia: The Therapeutic Benefits of Risperidone Plus Add-On Dextromethorphan. J Neuroimmune Pharmacol 7, 656–664 (2012). https://doi.org/10.1007/s11481-012-9382-z
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DOI: https://doi.org/10.1007/s11481-012-9382-z