Functional Connectivity and Associated Neuropeptides Variations in Treatment Resistant Schizophrenia Patients: Treatment Efficacy of add-on Sodium Benzoate
Although antipsychotic is effective for schizophrenia, however, still certain proportion of patients were not responsive to treatment. Treatment resistant schizophrenia (TRS) is accompanied by function decline and heavy burden. In recent decades, the biological mechanism of schizophrenia extended from dopamine theory to the role of glutamate system. This shift could be an alternative pathway to developing the treatment of TRS. Sodium benzoate (SB) could be an option as a glutamatergic agent for the patients with TRS. However, most evidence of SB is for treating patients with schizophrenia and other mental disorders but the evidence for treating patients with TRS is scarce. To predict the treatment response of SB will be an urgent topic in the future. Little is known about the precise medicine for treating patients with TRS. The present project will extend our pilot randomized clinical trial on SB for TRS. A total of 90 patients with TRS will be enrolled from three centers and will be assigned to 8 weeks of treatment with SB or placebo (2:1). A comprehensive battery of potential markers will be employed, including 1H- magnetic resonance spectroscopy (MRS), brain functional connectivity, genotyping, immune biomarkers, cognitive function, and clinical characteristics. The efficacy of SB on TRS will be confirmed in this project. Predictors for treatment response will be identified. Artificial intelligence algorithms will be used for probing the feasibility of precision medicine.
• Fulfil the DSM5 criteria for schizophrenia or schizoaffective disorder
• Research criteria for treatment resistance: little or no symptomatic response to multiple (at least two) antipsychotic treatment of an adequate duration (at least 6 weeks) and adequate doses (equivalent to at least 600 milliequivalent (meq)/day of chlorpromazine)
• 6 month period without remission (i.e. ≥4 item-score for the positive symptoms on PANSS scale , especially delusional thoughts, conceptual disorganisation, excitements, grandiosity, hallucinatory behaviour, excitement, persecution, and hostility)
• The persistence of illness was defined as a score of ≥4 (moderately ill) on the severity of illness subscale of the Clinical Global Impression scale (CGI-S), and a lack of stable period of good social occupational function.