Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Victoria, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, 161 Barry Street, Carlton South, Victoria 3053, Australia; Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Victoria, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, 161 Barry Street, Carlton South, Victoria 3053, Australia; IMPACT Strategic Research Centre, Deakin University, School of Medicine, Barwon Health, P.O. Box 291, Geelong 3220, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, 3052 Parkville, Australia.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:69-75. doi: 10.1016/j.pnpbp.2014.10.002. Epub 2014 Oct 12.
Schizophrenia is a chronic and often debilitating disorder in which stage of illness appears to influence course, outcome, prognosis and treatment response. Current evidence suggests roles for oxidative, neuroinflammatory, neurotrophic, apoptotic, mitochondrial and glutamatergic systems in the disorder; all targets of N-acetyl cysteine (NAC). A double blind, placebo controlled trial suggested NAC to be beneficial to those diagnosed with schizophrenia. The current manuscript aims to investigate duration of the illness as a key factor that may be modulating the response to NAC in the participants who took part in the study. A sample of 121 participants were randomised in a double fashion to 24 weeks (placebo=62; NAC=59). Clinical and functional variables were collected over the treatment period. Duration of the illness at baseline was grouped into <10 years, 10-<20 years and >20 years. Mixed Model Repeated Measures Analysis was used to explore the effect of illness duration on response to treatment with NAC. A significant interaction between duration of the illness and response to treatment with NAC was consistently found for positive symptoms and functional variables, but not for negative or general symptoms or for side effect related outcomes. The pattern of changes suggests that this mediator effect of duration of illness in response to treatment is more evident in those participants with 20 years or more of illness duration. Our results suggest a potential advantage of adjunctive NAC over placebo on functioning and positive symptoms reduction in those patients with chronic schizophrenia. This has potential for suggesting stage specific treatments.
精神分裂症是一种慢性且常使人衰弱的疾病，疾病阶段似乎会影响病程、结果、预后和治疗反应。目前的证据表明，氧化、神经炎症、神经营养、细胞凋亡、线粒体和谷氨酸能系统在该疾病中起作用；这些都是 N-乙酰半胱氨酸（NAC）的作用靶点。一项双盲、安慰剂对照试验表明，NAC 对被诊断为精神分裂症的患者有益。本手稿旨在研究疾病持续时间作为一个关键因素，可能会调节参与研究的参与者对 NAC 的反应。121 名参与者被随机分为双盲 24 周（安慰剂=62；NAC=59）。在治疗期间收集了临床和功能变量。将基线时的疾病持续时间分为<10 年、10-<20 年和>20 年。混合模型重复测量分析用于探索疾病持续时间对 NAC 治疗反应的影响。在阳性症状和功能变量方面，始终发现疾病持续时间与 NAC 治疗反应之间存在显著的交互作用，但在阴性或一般症状或与副作用相关的结果方面则没有。变化模式表明，在疾病持续时间超过 20 年的参与者中，这种疾病持续时间对治疗反应的中介效应更为明显。我们的结果表明，在慢性精神分裂症患者中，辅助 NAC 比安慰剂在功能和阳性症状减轻方面具有潜在优势。这为提出特定阶段的治疗方法提供了潜力。
