Early Detection of Risk Factors for Bipolar Mania

描述(由申请人提供)：这是一份R21申请，要求对成人发作的双相情感障碍的前驱症状(即躁狂前期)进行初步研究。试点工作被认为是证明双相情感障碍前驱概念的可行性的关键，这一概念仍然存在争议，研究也很少。被确认为前驱的受试者构成了双相情感障碍的新风险人群，这种群体基于早期阈值下临床体征和症状的存在，而不是更传统的根据家族病史选择受试者的遗传高风险方法。我们的研究小组是首批将临床高危(CHR)方法应用于精神分裂症干预的小组之一，目前该方法在整个领域得到了广泛采用。像精神分裂症一样，双相情感障碍是一种慢性的、高度虚弱的疾病，据推测有一个发展过程。因此，有人建议，专门为躁狂前期症状量身定做的CHR策略在改变病程方面可能是有效的。然而，与此同时，很明显，双相障碍在识别前驱期方面提出了独特的挑战。因此，必须进行广泛的先导性研究，使慢性阻塞性肺疾病的策略适应双相情感障碍的具体性质。拟议的为期两年的试点研究将包括四组青少年，每组40人，年龄从13岁到18岁不等。这些组包括：1)躁狂症高危人群(CHR-M)，以两种或两种以上阈值以下躁狂症状为特征的高危人群；2)年龄、性别和SES相匹配的患者对照组，包括在过去两年内被诊断为双相I型的青少年，3)临床精神分裂症高危青少年(CHR-SZ)，以及4)匹配的健康对照组。第三组和第四组将通过独立资助的RAP家长计划免费提供给拟议的应用程序，这是一项正在进行的关于青少年精神分裂症风险的研究。这项先导性研究的目标是：1)确定招募chr-M青少年样本的可行性；2)提供发育前驱体结构的初步横断面验证；3)进行短期6个月的随访，以确定选定的内表型和危险因素的稳定性；4)通过比较chr-M和chr-SZ受试者来评估双相情感障碍的特异性；5)初步确定短期(6个月)的临床结果。收集的数据是启动对双相先兆的更大规模的前瞻性研究的必要的第一步，从长远来看，也是启动有效的早期干预的关键第一步。公共卫生相关性：预防双相情感障碍将减轻个人和家庭的困难以及给社会造成的经济损失。这项自然主义的先导性研究为预防迈出了关键的第一步，提供了证据，证明临床和内表型危险因素可以在完全双相情感障碍发病之前被识别出来。对双相情感障碍高危个体的早期识别和研究将有助于阐明该疾病的神经发育基础，并导致有针对性的预防性干预。

DESCRIPTION (provided by applicant): This is an R21 application for a pilot study of the prodromal (i.e., pre-manic) phase of adult onset bipolar disorder. Pilot work is considered essential for demonstrating the viability of the prodromal concept in bipolar disorder, which remains controversial and little studied. Subjects identified as prodromal constitute a new risk population for bipolar disorder, one that is based on the presence of early subthreshold clinical signs and symptoms in contrast with the more traditional genetic high risk approach which selects subjects according to family history of illness. Our research group was among the first to apply a clinical high risk (CHR) approach to intervention in schizophrenia, now widely adopted throughout the field. Like schizophrenia, bipolar disorder is a chronic, highly debilitating illness with a presumed developmental course. It is thus proposed that a CHR strategy tailored specifically for the pre-mania prodrome might be effective in altering the course of illness. At the same time, however, it is clear that bipolar disorder presents unique challenges in the identification of a prodromal phase. It is therefore essential to do extensive pilot research to adapt the CHR strategy to the specific nature of the bipolar illness. The proposed two year pilot study will include four groups of 40 adolescents each, ranging in age from 13-18. These groups include: 1) CHR for Mania (CHR-M), the at-risk group of primary interest, characterized by two or more manic symptoms at subthreshold intensity, 2) a patient comparison group, matched for age, gender and SES, consisting of adolescents diagnosed with bipolar I within the previous two years, 3) adolescents at clinical high risk for schizophrenia (CHR-SZ), and 4) matched healthy controls. Groups 3 and 4 will be available, at no cost to the proposed application, through the independently funded RAP parent program, an ongoing study of adolescents at risk for schizophrenia. The goals of this pilot study are to: 1) establish feasibility in recruiting a sample of CHR-M adolescents; 2) provide preliminary cross-sectional validation of the developmental prodromal construct; 3) conduct short-term six-month follow-ups to establish the stability of selected endophenotypes and risk factors; 4) assess specificity to bipolar disorder by comparing CHR-M and CHR-SZ subjects and 5) preliminarily determine short term (6 month) clinical outcome. The data collected is the essential first step for launching a larger, prospective study of the bipolar prodrome and, in the long term, for initiating effective early intervention. PUBLIC HEALTH RELEVANCE: Prevention of bipolar disorder will relieve personal and family hardship and economic loss to society. This naturalistic pilot study represents a critical first step towards prevention by providing evidence that clinical and endophenotypic risk factors can be identified prior to the onset of full bipolar disorder. Early identification and study of individuals at high-risk for bipolar disorder will help elucidate the neurodevelopmental underpinnings of the disorder and lead to targeted preventative interventions.