State University of New York at Binghamton.
Dev Psychopathol. 2013 Nov;25(4 Pt 2):1347-57. doi: 10.1017/S0954579413000655.
The endophenotype is central to modern developmental psychopathology studies. It is used in studies seeking to connect the genetic substrates of the panoply of major mental disorders with processes, tapped by laboratory and other assessment measures, in the genotype to a behavior/psychopathology pathway. Proposed originally by Gottesman and Shields (1972; Shields & Gottesman, 1973) 41 years ago, the endophenotype concept has gained widespread traction in psychopathology research since the Gottesman and Gould (2003) review. Other concepts broadly related to the endophenotype notion have also generated discussion in experimental and developmental psychopathology research. One is the intermediate phenotype, a concept proffered as a putative alternative formulation to the endophenotype. Another concept in this intellectual vein is biomarker. The terms endophenotype, intermediate phenotype, and biomarker have often been used interchangeably in the psychiatric literature, yielding conceptual confusion. However, these three terms are not fungible. The recent Research Domain Criteria proposal from the National Institute of Mental Health has emphasized selected underlying processes thought to be of developmental etiologic significance to psychopathology. These selected processes will be the focus of energetic future research efforts, many of which will make use of the endophenotype and biomarker research paradigms. In this context, the concepts of endophenotype, intermediate phenotype, and biomarker are examined critically and contrasted in terms of meaning, intention, clarity, and intellectual history. This analysis favors use of the endophenotype concept in genetically informed laboratory and neuroscience studies of psychopathology. The term intermediate phenotype is perhaps best restricted to its originally defined meaning in genetics. Biomarker is used to denote objectively measured biological antecedents or consequences of normal or pathogenic processes or a physiologic response to a therapeutic intervention.
内表型是现代发展心理病理学研究的核心。它被用于研究，旨在将多种主要精神障碍的遗传基质与通过实验室和其他评估措施获得的、连接基因型与行为/精神病理学途径的过程联系起来。该概念最初由 Gottesman 和 Shields（1972；Shields & Gottesman，1973）于 41 年前提出，自 Gottesman 和 Gould（2003）的综述以来，在内表型概念已在精神病理学研究中得到广泛应用。其他与内表型概念广泛相关的概念也在实验和发展心理病理学研究中引起了讨论。一个是中间表型，这是作为内表型的替代假设提出的概念。另一个与这一概念有关的概念是生物标志物。在精神病学文献中，内表型、中间表型和生物标志物这三个术语经常互换使用，导致概念混淆。然而，这三个术语并不具有相同的含义。最近，美国国家心理健康研究所的研究领域标准提案强调了被认为对精神病理学具有发展病因学意义的选定潜在过程。这些选定的过程将成为未来研究的重点，其中许多研究将利用内表型和生物标志物研究范式。在这种情况下，批判性地检查了内表型、中间表型和生物标志物的概念，并从意义、意图、清晰度和知识历史等方面进行了对比。这项分析有利于在遗传信息丰富的精神病理学实验室和神经科学研究中使用内表型概念。中间表型这个术语最好保留在其在遗传学中的最初定义。生物标志物用于表示正常或致病过程的客观测量的生物学前因或后果，或对治疗干预的生理反应。
