Early Detection of Risk Factors for Bipolar Mania

描述（由申请人提供）：这是一份R21申请，用于成人发作双相情感障碍前驱期（即躁狂前期）的试点研究。试点工作被认为是必要的证明可行性的前驱症状的概念在双相情感障碍，这仍然是有争议的，很少研究。被确定为前驱的受试者构成了新的双相情感障碍风险人群，这是基于早期阈下临床体征和症状的存在，与更传统的根据家族史选择受试者的遗传高风险方法形成对比。我们的研究小组是最早将临床高风险（CHR）方法应用于精神分裂症干预的研究小组之一，该方法现已在整个领域广泛采用。与精神分裂症一样，双相情感障碍是一种慢性、高度衰弱的疾病，有一个假定的发展过程。因此，建议专门为躁狂症前前驱量身定制的CHR策略可能有效地改变病程。然而，与此同时，很明显，双相情感障碍在前驱期的识别方面提出了独特的挑战。因此，必须进行广泛的试点研究，以使CHR战略适应双相情感障碍的具体性质。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。这些组包括：1)躁狂症CHR （CHR- m)，主要关注的高危组，以两种或两种以上阈下强度的躁狂症状为特征；2)患者对照组，年龄、性别和社会经济地位相匹配，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家长项目（一项正在进行的针对有精神分裂症风险的青少年的研究）免费提供给拟议的申请。本初步研究的目的是：1)确定招募CHR-M青少年样本的可行性；2)对发展性前驱结构提供初步的横断面验证；3)进行为期6个月的短期随访，确定所选内表型和危险因素的稳定性；4)通过比较cr - m和cr - 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）临床结果。收集的数据是开展更大规模的双相前驱症状前瞻性研究的重要第一步，从长远来看，是开展有效的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和社会的经济损失。这项自然主义的初步研究为预防提供了关键的第一步，提供了临床和内源性危险因素可以在完全双相情感障碍发病之前确定的证据。早期识别和研究双相情感障碍高危个体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.