Gould T D, Gottesman I I
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH, HHS, Bethesda, MD 20892, USA.
Genes Brain Behav. 2006 Mar;5(2):113-9. doi: 10.1111/j.1601-183X.2005.00186.x.
Endophenotypes are quantifiable components in the genes-to-behaviors pathways, distinct from psychiatric symptoms, which make genetic and biological studies of etiologies for disease categories more manageable. The endophenotype concept has emerged as a strategic tool in neuropsychiatric research. This emergence is due to many factors, including the modest reproducibility of results from studies directed toward etiologies and appreciation for the complex relationships between genes and behavior. Disease heterogeneity is often guaranteed, rather than simplified, through the current diagnostic system; inherent benefits of endophenotypes include more specific disease concepts and process definitions. Endophenotypes can be neurophysiological, biochemical, endocrine, neuroanatomical, cognitive or neuropsychological. Heritability and stability (state independence) represent key components of any useful endophenotype. Importantly, they characterize an approach that reduces the complexity of symptoms and multifaceted behaviors, resulting in units of analysis that are more amenable to being modeled in animals. We discuss the benefits of more direct interpretation of clinical endophenotypes by basic behavioral scientists. With the advent of important findings regarding the genes that predispose to psychiatric illness, we are at an important crossroads where, without anthropomorphizing, animal models may provide homologous components of psychiatric illness, rather than simply equating to similar (loosely analogized) behaviors, validators of the efficacy of current medications or models of symptoms. We conclude that there exists a need for increased collaboration between clinicians and basic scientists, the result of which should be to improve diagnosis, classification and treatment on one end and to increase the construct relevance of model organisms on the other.
内表型是基因到行为途径中的可量化成分，有别于精神症状，这使得对疾病类别的病因进行遗传和生物学研究更易于管理。内表型概念已成为神经精神疾病研究中的一种战略工具。这一概念的出现得益于多种因素，包括针对病因的研究结果再现性一般，以及对基因与行为之间复杂关系的认识。通过当前的诊断系统，疾病异质性往往得以保证而非简化；内表型的内在优势包括更具体的疾病概念和过程定义。内表型可以是神经生理、生化、内分泌、神经解剖、认知或神经心理方面的。遗传性和稳定性（状态独立性）是任何有用的内表型的关键组成部分。重要的是，它们描述了一种降低症状和多方面行为复杂性的方法，从而产生更适合在动物中建模的分析单元。我们讨论了基础行为科学家对临床内表型进行更直接解读的益处。随着有关易患精神疾病基因的重要发现的出现，我们正处于一个重要的十字路口，即不进行拟人化的情况下，动物模型可能提供精神疾病的同源成分，而不仅仅等同于相似（松散类比）的行为、当前药物疗效的验证或症状模型。我们得出结论，临床医生和基础科学家之间需要加强合作，其结果一方面应改善诊断、分类和治疗，另一方面应提高模式生物的构建相关性。
