Early Intervention for Youth At-Risk for Bipolar Disorder

对有双相情感障碍风险的青少年进行早期干预

• 批准号: 10189024
• 负责人: TINA R GOLDSTEIN
• 金额: $ 66.44万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10189024
• 关键词: Adolescence; Adolescent; Adult; Advisory Committees; Affect; Affective; Age; Area; Behavior; Biological; Biological Markers; Bipolar Disorder; Brain Diseases; Categories; Cellular Phone; Child; Chronic; Chronic Disease; Circadian Dysregulation; Circadian Rhythms; Clinical; Clinical assessments; Communities; Data; Data Collection; Development; Dimensions; Disease; Early Intervention; Evidence based intervention; Evidence based treatment; Exhibits; Family; Family member; Feedback; Health Care Costs; Impairment; Individual; Intake; Intervention; Investigational Therapies; Manic; Measurable; Measures; Mediating; Meta-Analysis; Methods; Mood Disorders; Moods; Morbidity - disease rate; National Institute of Mental Health; Onset of illness; Outcome; Outcome Study; Parents; Participant; Pathway interactions; Patient Self-Report; Pattern; Prevention; Prevention approach; Psychopathology; Public Health; Randomized; Recording of previous events; Reporting; Research; Risk; Risk Factors; Role; Secure; Severity of illness; Signal Transduction; Sleep; Sleep disturbances; Strategic Planning; Stress; Suicide; Symptoms; Telephone; Testing; Time; Visit; Youth; actigraphy; anxiety symptoms; base; circadian; confirmatory trial; cost effective; cost effective measures; depressive symptoms; diaries; early experience; early onset; efficacious intervention; efficacy evaluation; functional disability; healthy lifestyle; high risk; high risk population; implementation science; improved; indicated prevention; innovation; modifiable risk; novel strategies; offspring; portability; preempt; prevent; primary outcome; programs; psychiatric symptom; randomized trial; response; social; substance use; suicide rate; telehealth; theories; tool; treatment adherence; treatment optimization; treatment response; young adult

Project Summary The most potent risk factor for the development of bipolar disorder (BP) is a first-degree family member with the illness; individuals with family history typically experience early BP onset and severe course. Up to 25% of offspring of parents with BP (OBP) develop BP by young adulthood. Using longitudinal data from the Pittsburgh Bipolar Offspring Study (BIOS MH60952), we developed a clinical tool (“risk calculator”) that reliably predicts an individual OBP’s 5-year risk for BP using a subset of demographic and clinical variables. This innovation offers the ideal opportunity to identify OBP at greatest risk and deliver indicated preventive interventions. Yet, to date, there is no evidence-based intervention for OBP who have not already developed mood disorder. Per the experimental therapeutics framework, promising approaches should be informed by, and target, factors that cause and sustain illness. Evidence suggests the pathway to develop BP among biologically vulnerable youth involves sleep and circadian disturbances. We adapted Interpersonal and Social Rhythm Therapy (IPSRT), an evidence-based treatment for BP adults that helps stabilize sleep/ circadian patterns, for adolescent OBP. In an open pilot and subsequent R34 randomized trial (MH091177), we established a preliminary efficacy signal for IPSRT with OBP. Our data further indicate IPSRT, but not Community Treatment Referral (CTR), engages and alters the hypothesized mechanism of action--sleep/ circadian disturbance, although practical barriers impacted treatment attendance. This proposal represents a vital next step in this program of research: a confirmatory efficacy trial of IPSRT delivered via telehealth for OBP (age 12-18, n=120) at elevated risk for BP onset via risk calculator score. All participants receive a baseline clinical assessment of psychiatric symptoms and sleep disturbance (via objective and subjective methods), followed by a feedback session. Youth are then randomized to receive 8 sessions of IPSRT or a manualized Healthy Lifestyle Behaviors Program (HL) delivered via secure videoconference to enhance attendance and reach. As clinically indicated, youth are offered CTR for any psychiatric symptoms/disorders identified at intake. Primary outcome domains over 18 months include subthreshold mania and affective lability--2 potent near-term predictors of BP in OBP that are themselves associated with morbidity and impairment. We will also further investigate the hypothesized mechanism underlying IPSRT-sleep/circadian disruption--across levels of analysis using reliable, cost-effective methods (actigraphy and daily diary ratings), and the contribution of interpersonal stress to sleep/circadian disruptions. Application of Implementation Science methods throughout maximizes ultimate scalability and feasibility if efficacious. We will also examine whether passive cellphone sensing may serve as a portable, cost-effective measure of mechanisms and outcomes to enhance ultimate dissemination. Research in this area has the potential to prevent, delay, or ameliorate the progression of this chronic and devastating illness in those at highest risk.

项目摘要 发展为双相情感障碍（BP）的最有力的危险因素是一级家庭成员， 有家族史的人通常会经历早期BP发作和严重的病程。高达25% 的BP（OBP）父母的后代在成年早期患上BP。使用纵向数据从 匹兹堡双极子代研究（BIOS MH 60952），我们开发了一种临床工具（“风险计算器”）， 使用人口统计学和临床变量的子集可靠地预测个体OBP的5年BP风险。 这项创新提供了理想的机会，以确定OBP的最大风险，并提供指示的预防 干预措施。然而，到目前为止，还没有证据为基础的干预OBP谁还没有发展 情绪障碍根据实验治疗学框架，有希望的方法应该被告知， 和目标，导致和维持疾病的因素。有证据表明， 生理脆弱的青少年包括睡眠和昼夜节律紊乱。我们调整了人际关系， 社交节律疗法（IPSRT），一种针对BP成人的循证治疗，有助于稳定睡眠/ 青少年OBP的昼夜节律模式。在一项开放性初步试验和随后的R34随机试验（MH 091177）中， 我们建立了IPSRT与OBP的初步疗效信号。我们的数据进一步表明IPSRT，但不是 社区治疗转诊（CTR），参与并改变了假设的作用机制-睡眠/ 昼夜节律紊乱，尽管实际障碍影响了治疗出勤率。该提案代表 这项研究计划的下一步是：通过远程医疗提供IPSRT的确证性疗效试验， OBP（年龄12-18岁，n=120）通过风险计算器评分，BP发作风险升高。所有参与者都会收到一份 精神症状和睡眠障碍的基线临床评估（通过客观和主观 方法），然后是反馈会议。然后，青少年被随机接受8次IPSRT或 通过安全的视频会议提供手册化的健康生活方式行为方案， 出席和到达。如有临床指征，青少年可接受CTR治疗任何精神症状/障碍 在接收时识别。超过18个月的主要结果领域包括阈下躁狂和情感性躁狂。 不稳定性--OBP中BP的2个有效的近期预测因子，其本身与发病率相关， 损伤我们还将进一步研究IPSRT-睡眠/昼夜节律的假设机制 中断--使用可靠的、具有成本效益的方法（活动记录仪和每日日记）进行跨级别分析 评分），以及人际压力对睡眠/昼夜节律中断的贡献。的应用 实施科学方法在整个最大限度地提高最终的可扩展性和可行性，如果有效。我们 还将研究被动式手机传感是否可以作为一种便携式，具有成本效益的措施， 加强最终传播的机制和成果。这一领域的研究有可能 预防、延迟或改善这种慢性和毁灭性疾病在高危人群中的进展。