Family-Focused Therapy as Early Treatment for Youth at Risk for Bipolar Disorder

青少年双相情感障碍（BD）与显著的功能障碍、治疗抵抗和高公共卫生费用相关。最近对双相障碍前驱形式的研究已经确定了症状性危险因素，这些因素增加了遗传易感儿童发展为双相障碍I或II的机会。我们研究的长期目标是降低风险青年患双相障碍的可能性或延缓双相障碍的完全表达。第一阶段（R34）的目的是开发和测试一种基于手册的早期心理教育干预——以家庭为中心的治疗（FFT）——以确定是否有必要进行大规模的早期干预试验，并进行更长的随访。FFT包括心理教育、沟通增强训练和解决问题技能训练，已被发现与药物治疗结合在预防双相障碍成人和青少年复发和稳定症状方面是有效的。本研究包括两个阶段，将在两个地点进行：科罗拉多大学（主要申请人地点；D. Miklowitz， PI）和斯坦福大学（次要地点；K. Chang, Co-PI）。在第一阶段，我们将确定12名年龄在9-17岁的推定前驱双相障碍儿童，他们符合高风险的研究标准（即，有一级亲属患有双相I或II型障碍，并符合未另行指定的双相障碍标准，循环精神障碍，或伴有轻躁狂症状的重度抑郁症）。在第一阶段，我们将为有双相障碍风险的儿童开发一份为期4个月、12个阶段的FFT手册，测试治疗师的忠实度量表，并根据临床医生和消费者的反馈以迭代的方式修改手册。我们将检查消费者对干预的接受程度，以及高危儿童症状和功能的前后变化（抑郁和躁狂评分，青少年纵向间隔随访的精神状态），为期一年。在第二阶段，我们将随机分配40名高风险儿童进行新手工FFT或常规治疗（TAU）比较。所有需要药物治疗的儿童都将按照最佳实践指南从研究精神科医生那里接受药物治疗。第二阶段的参与者将接受为期一年的检查，以检验FFT比TAU在降低躁狂和抑郁症状的严重程度、增加良好度过的时间、延迟首次躁狂、混合型或轻躁发作、改善功能、减少父母的痛苦和增加儿童获得适当心理健康服务的机会方面更有效的假设。数据分析方案强调混合效应回归和生存分析模型。第二阶段有40名参与者，在假设预期损耗率的情况下，可以很好地检测到大中型效应。试点试验将产生一份最终的治疗手册，该手册应可输出到其他治疗地点。它将产生目标结果的人群变异性估计，作为治疗的功能，这应该为开展更大规模的早期干预试验提供信息。首席研究员/项目主管：Miklowitz， David J。

Bipolar disorder (BD) in youth is associated with significant impairments in functioning, treatment-resistance, and high public health costs. Recent research on prodromal forms of BD have identified symptomatic risk factors which increase the chances that genetically predisposed children will develop BD I or II disorder. The long-term goal of our research is to reduce the likelihood of or delay the full expression of BD among at-risk youth. The aim of this first phase (R34) is to develop and test a manual-based early psychoeducational intervention - family-focused treatment (FFT) - to determine if a large-scale early intervention trial with longer follow-up is warranted. FFT, consisting of psychoeducation, communication enhancement training, and problem-solving skills training, has been found to be effective in combination with pharmacotherapy in preventing recurrences and stabilizing the symptoms of adults and adolescents with BD. The present study consists of two phases and will be conducted at two sites: the University of Colorado (primary applicant site; D. Miklowitz, PI) and Stanford University (secondary site; K. Chang, Co-PI). In Phase I, we will identify 12 children aged 9-17 with putative prodromal BD who meet study criteria for high risk (i.e., have a first-degree relative with bipolar I or II disorder and meet criteria for BD not otherwise specified, cyclothymia, or major depressive disorder with hypomanic symptoms). In phase I, we will develop a manual for a 4-month, 12-session version of FFT for children at risk for BD, test therapist fidelity scales, and revise the manual in an iterative fashion in response to clinician and consumer feedback. We will examine consumer acceptance of the intervention and pre/post changes in the symptoms and functioning of the at-risk children (depression and mania scores, psychiatric status on the Adolescent Longitudinal Interval Follow-up) over a 1-year period. In phase II, we will randomly assign 40 high-risk children to either the newly manualized FFT or a treatment-as-usual (TAU) comparison. All children who require pharmacotherapy will receive it from study psychiatrists following best- practice guidelines. Participants in phase II will be examined over one year to test the hypothesis that FFT is more effective than TAU in reducing the severity of manic and depressive symptoms, increasing the amount of time spent well, delaying the onset of first manic, mixed or hypomanic episodes, improving functioning, decreasing distress among parents, and increasing the child's access to appropriate mental health services. The data analytic plan emphasizes mixed effects regression and survival analytic models. With 40 participants, phase II is well-powered to detect large and medium effect sizes assuming expected rates of attrition. The pilot trial will produce a finalized treatment manual that should be exportable to other treatment sites. It will yield estimates of population variability in targeted outcomes as a function of treatments, which should inform the development of a larger-scale early intervention trial. Principal Investigator/Program Director: Miklowitz, David J.