Huang Jing, Chen AnMei, Jin Hua, Liu Fangkun, Hei Gangrui, Teng Ziwei, Xiao Jingmei, Wu Renrong, Zhao Jingping, Davis John M, Shao Ping, Smith Robert C
Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, P. R. China.
Columbia University Mailman School of Public Health, New York, New York.
J Clin Psychiatry. 2025 Jan 20;86(1):24m15272. doi: 10.4088/JCP.24m15272.
There are few established treatments for negative symptoms in schizophrenia, which persist in many patients after positive symptoms are reduced. Oxidative stress, inflammation, and epigenetic modifications involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. We conducted a 24-week, double-blind, placebo-controlled study, in Hunan, China, to assess the effect of high-dose sulforaphane (Nutramax extra strength sulforaphane tablets glucoraphanin content 30 mg/ tablet) on reducing negative symptoms in antipsychotic-treated patients with schizophrenia. Participants were recruited from August 2020 to August 2022 and met criteria for schizophrenia. Participants were randomly assigned (2:1) to receive antipsychotics plus sulforaphane (1,700 mg Avmacol Extra Strength sulforaphane daily) or antipsychotics plus placebo for 24 weeks. Fifty-three patients treated with sulforaphane and 24 patients treated with placebo who had at least 1 postintervention clinical scale evaluation were analyzed. The primary outcome measure was change in the Positive and Negative Syndrome Scale (PANSS) negative symptoms. Sulforaphane-treated patients showed a significantly greater decrease in PANSS negative symptom total score ( = .01) and PANSS negative factor score ( = .02) than placebo-treated patients, with the most prominent difference occurring at 24 weeks ( ≤ .001) with a large effect size at this time point ( = 0.8). Sulforaphane's effect on decreasing negative symptoms was not mediated by changes in scores of depression or cognitive factors on the PANSS. The results of this study suggest that add-on high-dose sulforaphane may reduce negative symptoms in patients with schizophrenia. The clinical significance of this reduction in negative symptoms needs further evaluation. ClinicalTrials.gov identifier: NCT04521868.
精神分裂症的阴性症状几乎没有成熟的治疗方法，在许多患者中，阳性症状减轻后阴性症状仍会持续存在。氧化应激、炎症以及涉及组蛋白脱乙酰酶（HDAC）的表观遗传修饰与精神分裂症的病理生理学有关。萝卜硫素具有抗氧化特性，是一种HDAC抑制剂。我们在中国湖南进行了一项为期24周的双盲、安慰剂对照研究，以评估高剂量萝卜硫素（纽崔莱超强萝卜硫素片，萝卜硫苷含量30毫克/片）对减少接受抗精神病药物治疗的精神分裂症患者阴性症状的效果。参与者于2020年8月至2022年8月招募，符合精神分裂症标准。参与者被随机分配（2:1）接受抗精神病药物加萝卜硫素（每天1700毫克奥麦可超强萝卜硫素）或抗精神病药物加安慰剂，为期24周。对53名接受萝卜硫素治疗和24名接受安慰剂治疗且至少有1次干预后临床量表评估的患者进行了分析。主要结局指标是阳性和阴性症状量表（PANSS）阴性症状的变化。与安慰剂治疗的患者相比，萝卜硫素治疗的患者在PANSS阴性症状总分（P = 0.01）和PANSS阴性因子得分（P = 0.02）上的下降幅度明显更大，最显著的差异出现在24周时（P ≤ 0.001），此时效应量较大（Cohen's d = 0.8）。萝卜硫素对减少阴性症状的作用不是由PANSS上抑郁或认知因子得分的变化介导的。本研究结果表明，添加高剂量萝卜硫素可能会减少精神分裂症患者的阴性症状。这种阴性症状减少的临床意义需要进一步评估。ClinicalTrials.gov标识符：NCT04521868。
