Pole for Innovation in Neuropsychiatry, Institut de Recherche (IDR) Servier, 78290 Croissy-sur-Seine, France.
Inserm, U836, Physiopathologie du cytosquelette, Grenoble Institut des Neurosciences, 38700 Grenoble, France.
Nat Rev Drug Discov. 2016 Jul;15(7):485-515. doi: 10.1038/nrd.2016.28. Epub 2016 Mar 4.
Despite a lack of recent progress in the treatment of schizophrenia, our understanding of its genetic and environmental causes has considerably improved, and their relationship to aberrant patterns of neurodevelopment has become clearer. This raises the possibility that 'disease-modifying' strategies could alter the course to - and of - this debilitating disorder, rather than simply alleviating symptoms. A promising window for course-altering intervention is around the time of the first episode of psychosis, especially in young people at risk of transition to schizophrenia. Indeed, studies performed in both individuals at risk of developing schizophrenia and rodent models for schizophrenia suggest that pre-diagnostic pharmacotherapy and psychosocial or cognitive-behavioural interventions can delay or moderate the emergence of psychosis. Of particular interest are 'hybrid' strategies that both relieve presenting symptoms and reduce the risk of transition to schizophrenia or another psychiatric disorder. This Review aims to provide a broad-based consideration of the challenges and opportunities inherent in efforts to alter the course of schizophrenia.
尽管精神分裂症的治疗在近期没有取得进展,但我们对其遗传和环境病因的理解已经有了很大的提高,并且它们与神经发育异常模式的关系也变得更加清晰。这就提出了一种可能性,即“疾病修正”策略可能会改变这种使人衰弱的疾病的进程和结果,而不仅仅是缓解症状。改变病程的一个有希望的窗口期是在精神病首次发作前后,特别是在有向精神分裂症转化风险的年轻人中。事实上,在有发展为精神分裂症风险的个体和精神分裂症啮齿动物模型中进行的研究表明,在诊断前进行药物治疗和心理社会或认知行为干预,可以延缓或减轻精神病的出现。特别引人关注的是那些既能缓解现有症状,又能降低向精神分裂症或其他精神障碍转化风险的“混合”策略。本综述旨在广泛考虑改变精神分裂症病程所固有的挑战和机遇。