中国科学院心理研究所机构知识库

导致精神分裂症的原因一直以来都是世界级科学难题.因为精神分裂症的发病机制受到基因、环境与表观遗传等多种因素的动态影响.介于基因型与表型之间的内表型,为探讨精神分裂症的发病机制提供了一个整合的途径.本文综述了自2003年内表型概念提出以来的主要文献,分别就精神分裂症内表型的定义、意义、几种潜在内表型这三个方面进行评述,给精神分裂症内表型的研究绘制一个轮廓,揭示其对我们深入了解精神分裂症发病机制的意义.

The aetiology of schizophrenia has been a challenge in science for a long time. Genes play an important role in the aetiology of schizophrenia since the heritability of schizophrenia was found to be 44%–87%. But the identification of genes alone could not answer all the questions in the pathogenesis of schizophrenia. According to previous studies, there are 1–3 main genes, along with 5 minor genes that work together to influence disease onset. Moreover, schizophrenia is such a complex disorder that is affected by a variety of factors such as dynamic environment and epigenetic factors in addition to genetics. However, endophenotype could bridge the gap between genotype and phenotype, which offers an integrated way to investigate the pathogenesis of schizophrenia. Robust endophenotypes may allow the identification of genes downstream by linkage analysis. We have reviewed the literature since 2003 when the concept of endophenotype was first proposed. This review summarized and discussed the endophenotype approach in the context of schizophrenia in three main parts: the definition and criteria of an endophenotype, the implications of endophenotypes and potential endophenotypes in schizophrenia. First, we reviewed the most updated definition of endophenotype. Second, we reviewed the implication of endophenotypes in discerning the pathogenesis of schizophrenia. Third, we reviewed several potential endophenotypes of schizophrenia, including both traditional cognitive endophenotypes and newer cognitive endophenotypes, such as neurological soft signs, brain structure and functional connectivity. For the traditional cognitive endophenotypes, we reviewed their effect sizes in discriminating between patients with schizophrenia and healthy controls as well as their heritability. For the newer cognitive endophenotypes, however, more studies about their effect sizes and heritability are needed so that the meta-analysis studies could be conducted and provide data with more power to show the validation and usefulness of these endophenotypes. This information would help researchers select cognitive tasks more effectively. Several studies on neurological soft signs in schizophrenia have emerged recently. The effect sizes of the neurological soft sign between the patients and healthy control, the patients and non-psychotic first degree relatives were provided in the literature. Although twins studies have estimated the heritability range of neurological soft signs, more linkage studies are needed to investigate the genes downstream and how these associations affect the onset of schizophrenia. Brain structure and functional connectivity endophenotypes show generally high heritability in patients with schizophrenia, but the brain regions reported vary between studies. More studies are needed to reach a consensus on the specific brain regions with large effect size and heritability. Brain structure and functional connectivity are important endophenotypes because they are associated not only with brain function, but also with the biological neural mechanisms, which may promote our understanding of the aetiology of schizophrenia. Future research directions were further discussed.