Early Detection of Risk Factors for Bipolar Mania

及早发现双相躁狂的危险因素

• 批准号: 7471872
• 负责人: BARBARA A. CORNBLATT
• 金额: $ 19.62万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7471872
• 关键词: Adolescent; Adopted; Adult; Affect; Affective; Age; Anxiety; Area; Attenuated; Biological; Bipolar Disorder; Characteristics; Child; Chronic; Chronic Disease; Circadian Rhythms; Clinical; Cognitive deficits; Complex; DSM-IV; Data; Detection; Deterioration; Development; Diagnosis; Disease; Early Diagnosis; Early Intervention; Early identification; Economics; Evolution; Family; Family history of; Funding; Future; Gender; Genes; Genetic; Goals; Grant; Impairment; Incipient Schizophrenia; Individual; Intervention; Lead; Literature; Manic; Measures; Medicine; Mental Depression; Modeling; Nature; Neurocognitive Deficit; Outcome; Parents; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Pilot Projects; Platelet Factor 4; Population; Prevention; Prevention program; Prospective Studies; Psychiatry; Psychopathology; Public Health; Purpose; Range; Recruitment Activity; Relative (related person); Research; Research Project Grants; Risk; Risk Factors; Role; Sampling; Schizophrenia; Score; Severity of illness; Signs and Symptoms; Societies; Specificity; Staging; Symptoms; Testing; Time; Validation; Work; base; clinically relevant; comparison group; concept; cost; depressive symptoms; design; endophenotype; executive function; experience; follow-up; interest; programs; prospective; success; trait; trend; volunteer

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.

描述（由申请人提供）：这是对成人双相情感障碍前驱（即，前动物）阶段进行试验研究的R21应用。试验工作对于证明双相情感障碍的前驱概念的生存能力被认为是必不可少的，而双相情感障碍的生存能力仍然有争议且研究很少。被识别为前沿的受试者构成了躁郁症的一种新的风险人群，该风险基于早期阈值临床体征和症状的存在，与更传统的遗传高风险方法相反，该方法根据疾病的家族史选择受试者。我们的研究小组是最早采用临床高风险方法（CHR）方法来干预精神分裂症的人之一，该精神分裂症现在在整个领域广泛采用。像精神分裂症一样，双相情感障碍是一种慢性，高度令人衰弱的疾病，并具有推测的发育过程。因此，有人提出，专门针对狂热前虫的量身定制的CHR策略可能有效地改变了疾病。然而，同时很明显，双相情感障碍在鉴定前阶段时提出了独特的挑战。因此，必须进行广泛的试点研究以使CHR策略适应双相疾病的特定性质。拟议的两年试点研究将包括四组40个青少年，年龄在13-18岁之间。这些组包括：1）CHR的躁狂（CHR-M），这是高风险的主要兴趣组，其特征是在亚阈值强度下的两个或多个躁狂症状，2）一个患者比较组，与年龄，性别和SES相匹配，由在前两年内被诊断为双极i的青少年，在临床高风险中，schiz-s piltize chorthe chr s schiz-s chornize schiz-s Chrs chr and Chr and Chr and Chr s schizz）（3）。第3和第4组将通过独立资助的RAP父母计划无需支付拟议申请，这是对有精神分裂症风险的青少年的持续研究。这项试验研究的目标是：1）确定招募CHR-M青少年样本的可行性； 2）提供发育前驱构建体的初步横截面验证； 3）进行短期六个月的随访，以建立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受试者评估对躁郁症的特异性，5）初步确定短期（6个月）临床结果。收集到的数据是对躁郁症前瞻性进行更大的前瞻性研究的重要第一步，从长远来看，进行了有效的早期干预。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对社会的经济损失。这项自然主义的试点研究是通过提供证据表明可以在完全双相情感障碍发作之前确定临床和内表型危险因素的证据，这是迈向预防的关键第一步。早期鉴定和研究高风险的双相情感障碍将有助于阐明该疾病的神经发育基础，并导致针对性的预防干预措施。