Schizophrenia:a classic battle ground of nature versus nurture debate

精神分裂症:基因与环境交互作用的典型范例

Much has been learned about the etiology and pathogenesis of schizophrenia since the term was first used by Eugene Bleuler over a century ago to describe one of the most important forms of major mental illness to affect mankind.Both nature and nurture feature prominently in our understanding of the genesis of the overall risk of developing schizophrenia.We now have a firm grasp of the broad structure of the genetic architecture and several key environmental risk factors have been identified and delineated.However,much of the heritability of schizophrenia remains unexplained and the reported environmental risk factors do not explain all the variances not attributable to genetic risk factors.The biggest problem at present is that our understanding of the causal mechanisms involved is still in its infancy.In this review,we describe the extent and limits of our knowledge of the specific genetic/constitutional and non-genetic/environmental factors that contribute to the overall risk of schizophrenia.We suggest novel methods may be required to understand the almost certainly immensely complex multi-level causal mechanisms that contribute to the generation of the schizophrenia phenotype.

自从Eugene Bleuler于一个多世纪前以schizophrenia(精神分裂症)命名人类一种最重要的精神疾病以来,有关精神分裂症的发病机制一直是医学研究的重点之一.现今人们大多认为遗传和环境因素对精神分裂症的发病都具有重要的作用,也对一些重要的风险基因和环境因素有了一定的了解.然而,仍有很多精神分裂症的遗传因素并不清晰,且已知的环境风险因素并不能完全解释遗传因素以外的发病原因.究其根本在于我们对精神分裂症发病机制的理解仍然十分浅显.本文对目前已知的精神分裂症的遗传及环境风险因素加以阐述,并对一些有助于理解精神分裂症复杂病因的新方法与研究范式进行了展望.