Ross Randal G, Freedman Robert
Department of Psychiatry, University of Colorado Denver, Aurora, CO
Department of Psychiatry, University of Colorado Denver, Aurora, CO.
Schizophr Bull. 2015 Jul;41(4):824-34. doi: 10.1093/schbul/sbv054. Epub 2015 May 4.
Endophenotypes are disease-associated phenotypes that are thought to reflect the neurobiological or other mechanisms that underlie the more overt symptoms of a psychiatric illness. Endophenotypes have been critical in understanding the genetics, neurobiology, and treatment of schizophrenia. Because psychiatric illnesses have multiple causes, including both genetic and nongenetic risk factors, an endophenotype linked to one of the mechanisms may be expressed more frequently than the disease itself. However, in schizophrenia research, endophenotypes have almost exclusively been studied in older adolescents or adults who have entered or passed through the age of risk for the disorder. Yet, schizophrenia is a neurodevelopmental disorder where prenatal development starts a cascade of brain changes across the lifespan. Endophenotypes have only minimally been utilized to explore the perinatal development of vulnerability. One major impediment to the development of perinatally-useful endophenotypes has been the established validity criteria. For example, the criterion that the endophenotype be more frequently present in those with disease than those without is difficult to demonstrate when there can be a decades-long period between endophenotype measurement and the age of greatest risk for onset of the disorder. This article proposes changes to the endophenotype validity criteria appropriate to perinatal research and reviews how application of these modified criteria helped identify a perinatally-usable phenotype of risk for schizophrenia, P50 sensory gating, which was then used to propose a novel perinatal primary prevention intervention.
内表型是与疾病相关的表型，被认为反映了精神疾病更明显症状背后的神经生物学或其他机制。内表型在理解精神分裂症的遗传学、神经生物学和治疗方面至关重要。由于精神疾病有多种病因，包括遗传和非遗传风险因素，与其中一种机制相关的内表型可能比疾病本身更频繁地表现出来。然而，在精神分裂症研究中，几乎只在进入或已度过该疾病风险年龄的青少年或成年人中研究内表型。然而，精神分裂症是一种神经发育障碍，产前发育引发了贯穿一生的一系列大脑变化。内表型在探索围产期易感性发育方面的应用极少。围产期有用的内表型发展的一个主要障碍是既定的有效性标准。例如，当在内表型测量和疾病发病风险最高年龄之间可能存在数十年的间隔时，很难证明疾病患者比非患者更频繁出现内表型这一标准。本文提出了适用于围产期研究的内表型有效性标准的变化，并回顾了这些修改后的标准如何帮助识别精神分裂症围产期可用的风险表型——P50感觉门控，然后用它来提出一种新的围产期一级预防干预措施。
