Haller Chiara S, Padmanabhan Jaya L, Lizano Paulo, Torous John, Keshavan Matcheri
Department of Psychology, Harvard University 33 Kirkland street, Cambridge, MA 02138 USA ; Department of Psychiatry, Beth Israel Deaconess Medical Center 330 Brookline Avenue, Boston, MA 02215 USA.
Division of Public Psychiatry, Massachusetts Mental Health Center 75 Fenwood Road, Boston, MA 02115 USA ; Department of Psychiatry, Beth Israel Deaconess Medical Center 330 Brookline Avenue, Boston, MA 02215 USA.
F1000Prime Rep. 2014 Jul 8;6:57. doi: 10.12703/P6-57. eCollection 2014.
Schizophrenia is a highly disabling disorder whose causes remain to be better understood, and treatments have to be improved. However, several recent advances have been made in diagnosis, etiopathology, and treatment. Whereas reliability of diagnosis has improved with operational criteria, including Diagnostic and Statistical Manual of Mental Disorders, (DSM) Fifth Edition, validity of the disease boundaries remains unclear because of substantive overlaps with other psychotic disorders. Recent emphasis on dimensional approaches and translational bio-behavioral research domain criteria may eventually help move toward a neuroscience-based definition of schizophrenia. The etiology of schizophrenia is now thought to be multifactorial, with multiple small-effect and fewer large-effect susceptibility genes interacting with several environmental factors. These factors may lead to developmentally mediated alterations in neuroplasticity, manifesting in a cascade of neurotransmitter and circuit dysfunctions and impaired connectivity with an onset around early adolescence. Such etiopathological understanding has motivated a renewed search for novel pharmacological as well as psychotherapeutic targets. Addressing the core features of the illness, such as cognitive deficits and negative symptoms, and developing hypothesis-driven early interventions and preventive strategies are high-priority goals for the field. Schizophrenia is a severe, chronic mental disorder and is among the most disabling disorders in all of medicine. It is estimated by the National Institute of Mental Health (NIMH) that 2.4 million people over the age of 18 in the US suffer from schizophrenia. This illness typically begins in adolescence and derails the formative goals of school, family, and work, leading to considerable suffering and disability and reduced life expectancy by about 20 years. Treatment outcomes are variable, and some people are successfully treated and reintegrated (i.e. go back to work). Despite the effort of many experts in the field, however, schizophrenia remains a chronic relapsing and remitting disorder associated with significant impairments in social and vocational functioning and a shortened lifespan. Comprehensive treatment entails a multi-modal approach, including psychopharmacology, psychosocial interventions, and assistance with housing and financial sustenance. Research to date suggests a network of genetic, neural, behavioral, and environmental factors to be responsible for its development and course. This article aims to summarize and explain recent advancements in research on schizophrenia, to suggest how these recent discoveries may lead to a better understanding and possible further development of effective therapies, and to highlight the paradigm shifts that have taken place in our understanding of the diagnosis, etiopathology, and treatment.
精神分裂症是一种致残性很强的疾病,其病因仍有待深入了解,治疗方法也有待改进。然而,近年来在诊断、病因病理学和治疗方面已取得了一些进展。虽然随着包括《精神疾病诊断与统计手册》(DSM)第五版在内的操作性标准的出台,诊断的可靠性有所提高,但由于与其他精神障碍存在实质性重叠,该疾病边界的有效性仍不明确。最近对维度方法和转化生物行为研究领域标准的重视,最终可能有助于朝着基于神经科学的精神分裂症定义迈进。现在认为精神分裂症的病因是多因素的,多个小效应和较少的大效应易感基因与多种环境因素相互作用。这些因素可能导致神经可塑性在发育过程中发生改变,表现为一系列神经递质和神经回路功能障碍以及连接受损,发病时间大约在青春期早期。这种病因病理学认识促使人们重新寻找新的药理学和心理治疗靶点。针对该疾病的核心特征,如认知缺陷和阴性症状,并制定基于假设的早期干预和预防策略,是该领域的首要目标。精神分裂症是一种严重的慢性精神障碍,是所有医学疾病中致残性最强的疾病之一。据美国国立精神卫生研究所(NIMH)估计,美国18岁以上的人群中有240万人患有精神分裂症。这种疾病通常始于青春期,打乱了学业、家庭和工作等成长目标,导致巨大的痛苦和残疾,并使预期寿命缩短约20年。治疗结果因人而异,有些人得到了成功治疗并重新融入社会(即重返工作岗位)。然而,尽管该领域的许多专家付出了努力,精神分裂症仍然是一种慢性复发和缓解性疾病,与社会和职业功能的显著损害以及寿命缩短有关。综合治疗需要采取多模式方法,包括心理药理学、心理社会干预以及住房和经济维持方面的援助。迄今为止的研究表明,遗传、神经、行为和环境因素网络是其发展和病程的原因。本文旨在总结和解释精神分裂症研究的最新进展,提出这些最新发现如何可能导致对有效治疗方法有更好的理解和可能的进一步发展,并强调在我们对诊断、病因病理学和治疗的理解中发生的范式转变。