Hei Gangrui, Smith Robert C, Li Ranran, Ou Jianjun, Song Xueqing, Zheng Yingjun, He Yiqun, Arriaza Jen, Fahey Jed W, Cornblatt Brian, Kang Dongyu, Yang Ye, Huang Jing, Wang Xiaoyi, Cadenhead Kristin, Zhang Mimei, Davis John M, Zhao Jingping, Jin Hua, Wu Renrong
Department of Psychiatry, and National Clinical Research Center for Mental Disorders,the Second Xiangya Hospital of Central South University; China National Clinical Research Center on Mental Disorders; Hunan Medical Center for Mental Health, China National Technology Institute on Mental Disorders; Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan 410011, China.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China.
Schizophr Bull Open. 2022 Mar 7;3(1):sgac024. doi: 10.1093/schizbullopen/sgac024. eCollection 2022 Jan.
Cognitive symptoms are associated with significant dysfunction in schizophrenia. Oxidative stress and inflammation involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. The objective of this study was to determine the efficacy of sulforaphane on cognition dysfunction for patients with schizophrenia.
This double-blind randomized 22-week trial of patients with first-episode schizophrenia was conducted in four psychiatric institutions in China. Patients were randomized to three groups (two doses of sulforaphane vs. placebo) and symptomatic and cognitive assessments were completed at multiple times. The primary outcome measure was change in the MATRICS Composite score. The secondary outcomes were change in MATRICS Domain scores, PANSS Total Scores and change in side-effects.
A total of 172 patients were randomized and 151 patients had at least one follow up evaluation. There were no significant effects of sulforaphane, on the primary outcome, MATRICS overall composite score. However, on secondary outcomes, sulforaphane did significantly improve performance scores on MATRICS battery Domains of spatial working memory ( = 5.68, = 0.004), reasoning-problem solving ( = 2.82, = 0.063), and verbal learning ( = 3.56, = 0.031). There were no effects on PANSS symptom scores. Sulforaphane was well tolerated.
Although the primary outcome was not significant, improvement in three domains of the MATRICS battery, suggests a positive cognitive effect on some cognitive functions, which warrants further clinical trials to further assess whether sulforaphane may be a useful adjunct for treating some types of cognitive deficits in schizophrenia.
认知症状与精神分裂症的显著功能障碍相关。涉及组蛋白去乙酰化酶（HDAC）的氧化应激和炎症已被认为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。本研究的目的是确定萝卜硫素对精神分裂症患者认知功能障碍的疗效。
这项针对首发精神分裂症患者的双盲随机22周试验在中国的四家精神病机构进行。患者被随机分为三组（两种剂量的萝卜硫素与安慰剂组），并在多个时间点完成症状和认知评估。主要结局指标是MATRICS综合评分的变化。次要结局指标是MATRICS领域评分的变化、阳性和阴性症状量表（PANSS）总分以及副作用的变化。
共有172名患者被随机分组，151名患者至少进行了一次随访评估。萝卜硫素对主要结局指标MATRICS总体综合评分没有显著影响。然而，在次要结局指标方面，萝卜硫素确实显著提高了MATRICS成套测验中空间工作记忆领域（t = 5.68，P = 0.004）、推理 - 解决问题领域（t = 2.82，P = 0.063）和言语学习领域（t = 3.56，P = 0.031）的表现评分。对PANSS症状评分没有影响。萝卜硫素耐受性良好。
尽管主要结局不显著，但MATRICS成套测验三个领域的改善表明对某些认知功能有积极的认知作用，这值得进一步的临床试验来进一步评估萝卜硫素是否可能是治疗精神分裂症某些类型认知缺陷的有用辅助药物。
