Early Detection of Risk Factors for Bipolar Mania

描述（由申请人提供）：这是一项R21申请，用于前驱体（即，躁狂前期）阶段。试点工作被认为是必不可少的，以证明在双相情感障碍，这仍然是有争议的，很少研究前驱概念的可行性。被确定为前驱期的受试者构成了双相情感障碍的新风险人群，与根据家族病史选择受试者的更传统的遗传高风险方法相比，该风险人群基于早期阈下临床体征和症状的存在。我们的研究小组是第一个应用临床高风险（风险）方法干预精神分裂症的研究小组，现在已被广泛采用。像精神分裂症一样，双相情感障碍是一种慢性的、高度衰弱的疾病，有一个假定的发展过程。因此，建议一个专门为躁狂前前驱症状量身定制的治疗策略可能会有效地改变疾病的进程。然而，与此同时，很明显，双相情感障碍在确定前驱期方面提出了独特的挑战。因此，有必要进行广泛的试点研究，以适应双相情感障碍疾病的具体性质的治疗策略。这项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。这些团体包括：1）躁狂发作（CHR-M），主要关注的风险组，特征为阈值下强度的两种或更多种躁狂症状，2）患者对照组，年龄、性别和SES匹配，由过去两年内诊断为双相I型的青少年组成，3）精神分裂症临床高风险青少年（CHR-SZ），4）匹配的健康对照。第3组和第4组将通过独立资助的RAP父母计划提供，这是一项正在进行的对有精神分裂症风险的青少年的研究，对拟议的申请不收取任何费用。本试验研究的目的是：1）确定招募CHR-M青少年样本的可行性; 2）提供发育前驱期结构的初步横断面验证; 3）进行短期6个月随访，以确定选定的内表型和风险因素的稳定性; 4）通过比较CHR-M和CHR-SZ受试者来评估对双相情感障碍的特异性，以及5）初步确定短期（6个月）临床结果。收集的数据是开展双相前驱症状更大规模前瞻性研究的重要第一步，从长远来看，也是启动有效早期干预的重要第一步。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社会的经济损失。这项自然主义的试点研究代表了预防的关键第一步，提供了证据表明，临床和内表型风险因素可以在双相情感障碍发作前确定。早期识别和研究双相情感障碍的高危个体将有助于阐明该障碍的神经发育基础，并导致有针对性的预防干预。

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.