内表型方法在精神疾病研究中的应用

Application of Endophenotype Approach in Psychiatric Research

精神疾病在很大程度上受到遗传的影响，而对疾病的遗传学研究却没有得到一致的结论，内表型正是在这一背景下提出。内表型是可以通过生化测试或显微镜检查发现的内在的表现型，即内表型不是很明显的、外在的而是微观的、内在的，内表型比疾病的外在表现更接近疾病的生物学基础，更少受到外在因素的影响，因而通过内表型来研究疾病的遗传基因有着显着的优势。现有的精神疾病诊断和分类标准都是以临床症状和行为描述为基础的，缺少生物学基础，基于内表型的分析对建立疾病的诊断和分类的生物学基础是非常重要的。内表型可以是神经生理的，生物化学的，神经解剖的，认知的，神经心理学的测量。作为内表型需要满足与疾病共同存在，可遗传、状态独立，在家庭中和疾病共分离，在病人未发病亲属中比一般人群的比率要高等标准。该文在介绍了内表型的概念，说明了内表型的原理，优点与用处，以及作为内表型需要满足的标准之后，进而以几种常见的精神疾病（多动症、精神分裂症、抑郁症）为例说明了目前认知内表型研究的进展，其中反应抑制和工作记忆可以作为多动症的内表型，注意，言语记忆和工作记忆可以作为精神分裂症和抑郁症的内表型，文章回顾了它们作为内表型所满足的标准的相关文献。最后对内表型的研究做出了展望。

The identification of genes that contribute to a susceptibility to psychiatric disorders has been elusive using conventional genetic approaches. One problem to gene finding is that we cannot identify carriers of genes in the absence of manifest symptoms. Also， psychiatric diagnoses are likely to be heterogeneous in that not all people with the same diagnosis carry the same susceptibility genes. A new direction that appears encouraging is the identification of neurobiological or neurobehavioral characteristics associated with schizophrenia， or endophenotypes， that may be more closely linked to gene expression. Endophenotypes are internal phenotypes discovered by a “biochemical test or microscopic examination”， they are not the obvious and external but the microscopic and internal， endophenotypes are more approach the biological basis than the external manifestations， less affected by other factors so it has obvious advantages in studying the genetics of psychiatric disease. And the present diagnostic and classification systems are based on clinical manifestations and behavioral disease. And the present diagnostic and classification systems are based on clinical manifestations and behavioral descriptions， lack of biological basis， the endophenotype approach is of great importance in establishing the neurobiological basis of diagnostic and classification systems. Endophenotypes can be neurophysiologic， biochemical， neuroanatomical， cognitive， and neuropsychological measures. To be an andophenotype， it must fulfill some criteria：associate with the disease， heritable， stable or state-independent， cosegragate in the family， endophenotypes should have a higher rate in nonpsychotic relatives than in general population. The paper introduced the concept of endophenotype， illustrated its rational， advantages and usefulness， and the criteria that must be fulfilled， then take three common psychiatric diseases as examples to demonstrate the research development of endophenotypes， e.g.， response inhibition and working memory as endophenotypes of attention deficit╱hyperactivity disorder， attention， verbal memory and working memory as endophenotypes of schizophrenia and depression. At last， it points out the future directions of endophenotype research.