Tandon Rajiv, Keshavan Matcheri S, Nasrallah Henry A
University of Florida, 3706 Glin Circle, Tallahassee, FL 32309, United States.
Schizophr Res. 2008 Jul;102(1-3):1-18. doi: 10.1016/j.schres.2008.04.011. Epub 2008 Jun 2.
Although we have studied schizophrenia as a major disease entity over the past century, its causes and pathogenesis remain obscure. In this article, we critically review genetic and other epidemiological findings and discuss the insights they provide into the causes of schizophrenia. The annual incidence of schizophrenia averages 15 per 100,000, the point prevalence averages approximately 4.5 per population of 1000, and the risk of developing the illness over one's lifetime averages 0.7%. Schizophrenia runs in families and there are significant variations in the incidence of schizophrenia, with urbanicity, male gender, and a history of migration being associated with a higher risk for developing the illness. Genetic factors and gene-environment interactions together contribute over 80% of the liability for developing schizophrenia and a number of chromosomal regions and genes have been "linked" to the risk for developing the disease. Despite intensive research and spectacular advances in molecular biology, however, no single gene variation has been consistently associated with a greater likelihood of developing the illness and the precise nature of the genetic contribution remains obscure at this time. Environmental factors linked to a higher likelihood of developing schizophrenia include cannabis use, prenatal infection or malnutrition, perinatal complications, and a history of winter birth; the exact relevance or nature of these contributions is, however, unclear. How various genetic and environmental factors interact to cause schizophrenia and via which precise neurobiological mechanisms they mediate this effect is not understood. Etiological heterogeneity, complex patterns of gene-gene and gene-environment interaction, and inadequately elucidated schizophrenia pathophysiology are among the explanations invoked to explain our inadequate understanding of the etio-pathogenesis of schizophrenia. The ability to question some of our basic assumptions about the etiology and nature of schizophrenia and greater rigor in its study appear critical to improving our understanding about its causation.
尽管在过去一个世纪里我们一直将精神分裂症作为一种主要疾病实体进行研究，但其病因和发病机制仍不清楚。在本文中，我们批判性地回顾了遗传学及其他流行病学研究结果，并讨论了它们为精神分裂症病因提供的见解。精神分裂症的年发病率平均为每10万人中15例，时点患病率平均约为每1000人中4.5例，一生中患该病的风险平均为0.7%。精神分裂症具有家族聚集性，其发病率存在显著差异，城市化、男性以及有移民史与患该病的较高风险相关。遗传因素和基因 - 环境相互作用共同导致了超过80%的精神分裂症发病倾向，并且一些染色体区域和基因已被“关联”到患该病的风险。然而，尽管进行了深入研究且分子生物学取得了显著进展，但尚未发现单一基因变异与患该病的更高可能性始终相关，目前遗传因素的确切性质仍不清楚。与患精神分裂症可能性较高相关的环境因素包括使用大麻、产前感染或营养不良、围产期并发症以及冬季出生史；然而，这些因素的确切相关性或性质尚不清楚。各种遗传和环境因素如何相互作用导致精神分裂症以及它们通过哪些精确的神经生物学机制介导这种效应尚不清楚。病因异质性、基因 - 基因和基因 - 环境相互作用的复杂模式以及对精神分裂症病理生理学的阐释不足等，都是用来解释我们对精神分裂症病因发病机制理解不足的原因。对我们关于精神分裂症病因和本质的一些基本假设提出质疑以及在研究中更加严谨，对于提高我们对其病因的理解似乎至关重要。
