1/2-Early Intervention for Youth at Risk for Bipolar Disorder

1/2-对有双相情感障碍风险的青少年进行早期干预

• 批准号: 8239359
• 负责人: DAVID Jay MIKLOWITZ
• 金额: $ 78.8万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8239359
• 关键词: Acute; Adolescent; Adult; Affect; Affective; Affective Symptoms; Aftercare; Age; Amygdaloid structure; Arousal; Behavioral; Biological; Biostatistics Core; Bipolar Disorder; Caring; Characteristics; Clinical; Clinical Services; Colorado; Communication; Country; Diagnosis; Diagnostic; Disease; Early treatment; Education; Emotional; Emotions; Enrollment; Evaluation; Expressed Emotion; Face; Family; Family history of; Functional Magnetic Resonance Imaging; Future; Housing; Individual; Institutes; Intervention; Laboratories; Lead; Link; Major Depressive Disorder; Manic; Manuals; Measures; Mental Health Services; Mental disorders; Monitor; Moods; Morbidity - disease rate; National Institute of Mental Health; Outcome; Parents; Participant; Perception; Pharmacological Treatment; Pharmacotherapy; Phase; Prefrontal Cortex; Problem Solving; Procedures; Prospective Studies; Psychiatrist; Public Health; Randomized; Recording of previous events; Recovery; Recruitment Activity; Research; Risk; Sampling; Scanning; Severities; Site; Specific qualifier value; Strategic Planning; Structure; Symptoms; Testing; Training; Translations; Treatment Cost; Youth; arm; base; community setting; control trial; cost effective; cost effectiveness; depressive symptoms; disability; disturbance in affect; efficacy testing; emotion regulation; follow-up; hazard; high risk; hypomania; innovation; meetings; mood regulation; neuroimaging; novel; prevent; primary outcome; prospective; psychoeducation; psychoeducational; psychoeducational intervention; psychosocial; relating to nervous system; response; service utilization; stress resilience; sugar; symptomatic improvement; therapy development

DESCRIPTION (provided by applicant): This proposal is one of two linked applications (UCLA [D. Miklowitz] and Stanford [K. Chang]) in response to PAR-09-153, Collaborative R01s for Clinical and Services Studies of Mental Disorders. Despite the considerable public health burden of bipolar disorder (BD), no psychosocial interventions have been systematically applied to youth at high risk for developing the illness. Research on youth who are genetically predisposed to BD has identified clinical states with considerable risk for conversion to full threshold BD I or II disorder. We propose a multisite RCT to test the efficacy of a multi-faceted family-focused treatment for high- risk youth (FFT-HR). The 4 month intervention consists of psychoeducation, communication training, and problem solving and aims to reduce affective arousal, increase stress resilience, and increase capacities for emotion modulation. In a treatment development study, we found FFT-HR to be highly effective compared to a brief psychoeducational intervention in reducing affective symptoms and enhancing functioning among youth at high risk for BD, particularly those in high expressed emotion families. We will enroll 150 youth ages 9-17 who meet operationalized high-risk criteria for BD: (1) a diagnosis of BD not otherwise specified or major depressive disorder, with active symptoms in the past 1-2 weeks; and (2) at least one biological parent has a history of type I or type II BD. Following a diagnostic and family evaluation, we will randomly assign subjects to: (1) FFT-HR (12 sessions in 4 mos), or (2) enhanced care (EC; 3 weekly family education sessions followed by monthly individual support sessions over 4 mos). Participants who require pharmacotherapy will be treated by psychiatrists applying best-practice procedures. A subset of 60 youths will undergo pre- and post-treatment fMRI scans while performing two tasks shown to activate prefrontal-subcortical circuitry: a standard facial affect task of implicit emotion perception and an emotion regulation task. We will compare the magnitude of pre/post treatment changes in affective symptoms and functioning between subjects randomized to the two treatment arms, and the stability of changes over 2-4 years. We hypothesize that FFT-HR will be more effective than EC in (1) reducing the acute severity of mood symptoms and maintaining mood stability over 2-4 years, and (2) reducing the hazard of a first (hypo)manic episode and enhancing functioning. We hypothesize that indicators of high emotional arousal - pretreatment levels of expressed emotion in parents, emotional dysregulation in youth, and activation in prefrontal-subcortical limbic circuits (amygdala, dorsolateral and ventral prefrontal cortex) in youth - will be associated with a greater magnitude of response to FFT-HR. Finally, we will examine the impact of FFT-HR vs. EC on pre/post treatment changes in activation of limbic circuitry, and correlations between neural changes and symptom improvement over 4 mos. Consistent with the NIMH Strategic Plan, this study will facilitate the translation of a novel early intervention in community settings and identify mechanistic factors at the neural, clinical, and contextual levels that can be used to refine future treatments. PUBLIC HEALTH RELEVANCE: The proposed study is the first definitive trial of an early psychosocial intervention - family-focused treatment for high-risk youth (FFT-HR) - in comparison with brief psychoeducation in reducing the severity of affective morbidity, preventing or delaying the onset of fully syndromal mania, and enhancing functioning in youth at high risk for bipolar disorder. We hypothesize that responses to family intervention will be affected by individual-behavioral factors (degree of emotional dysregulation), family-contextual variables (level of expressed emotion), and neural factors (activation in prefrontal-subcortical limbic circuits that have been implicated in mood regulation). FFT-HR could prove to be a cost-effective and easily disseminable intervention, with great potential to prevent or ameliorate the natural progression of bipolar disorder and reduce individual disability and public health burden among high-risk youth.

描述（由申请人提供）：本提案是响应 PAR-09-153（精神障碍临床和服务研究协作 R01）的两个关联申请（加州大学洛杉矶分校 [D. Miklowitz] 和斯坦福大学 [K. Chang]）之一。尽管双相情感障碍（BD）给公共健康带来了相当大的负担，但尚未对罹患该疾病的高风险青少年进行系统的社会心理干预。对具有双相情感障碍遗传倾向的青少年的研究已确定，临床状态具有转化为全阈值双相情感障碍 I 型或 II 型疾病的相当大的风险。我们提出了一项多中心随机对照试验来测试针对高危青少年的多方面以家庭为中心的治疗（FFT-HR）的功效。为期 4 个月的干预包括心理教育、沟通训练和问题解决，旨在减少情感唤醒、提高抗压能力和情绪调节能力。在一项治疗开发研究中，我们发现，与简短的心理教育干预相比，FFT-HR 在减少双相情感障碍高危青少年的情感症状和增强功能方面非常有效，尤其是那些高表达情绪家庭的青少年。我们将招募 150 名 9-17 岁的青少年，他们符合 BD 的可操作高风险标准：（1）诊断为非特指的 BD 或重度抑郁症，并且在过去 1-2 周内有活动症状； (2) 至少一位亲生父母有 I 型或 II 型 BD 病史。经过诊断和家庭评估后，我们将随机分配受试者：(1) FFT-HR（4 个月内 12 次课程），或 (2) 强化护理（EC；每周 3 次家庭教育课程，随后每月进行超过 4 次的个人支持课程）莫）。需要药物治疗的参与者将由精神科医生采用最佳实践程序进行治疗。 60 名青少年将接受治疗前和治疗后的功能磁共振成像扫描，同时执行两项可激活前额皮质下回路的任务：内隐情绪感知的标准面部情感任务和情绪调节任务。我们将比较随机分配到两个治疗组的受试者之间治疗前/治疗后情感症状和功能的变化程度，以及 2-4 年变化的稳定性。我们假设 FFT-HR 在以下方面比 EC 更有效：(1) 降低情绪症状的严重程度并在 2-4 年内维持情绪稳定性；(2) 降低首次（轻）躁狂发作的风险并增强情绪稳定性。发挥作用。我们假设，高情绪唤醒的指标——父母表达情绪的治疗前水平、青少年的情绪失调以及青少年前额皮质下边缘回路（杏仁核、背外侧和腹侧前额叶皮质）的激活——将与更大幅度的情绪唤醒相关。对 FFT-HR 的响应。最后，我们将检查 FFT-HR 与 EC 对治疗前/后边缘回路激活变化的影响，以及 4 个月内神经变化和症状改善之间的相关性。与 NIMH 战略计划一致，这项研究将促进社区环境中新型早期干预的转化，并确定神经、临床和背景水平的机制因素，这些因素可用于完善未来的治疗。 公共健康相关性：拟议的研究是早期心理社会干预的第一个明确试验——对高危青少年进行以家庭为中心的治疗（FFT-HR）——与短期心理教育相比，在降低情感发病的严重程度、预防或延迟完全综合症性躁狂的发作，并增强双相情感障碍高风险青少年的功能。我们假设对家庭干预的反应将受到个人行为因素（情绪失调的程度）、家庭背景变量（表达情绪的水平）和神经因素（与情绪有关的前额皮质下边缘回路的激活）的影响。规定）。 FFT-HR 可能被证明是一种具有成本效益且易于传播的干预措施，在预防或改善双相情感障碍的自然进展以及减少高危青少年中的个人残疾和公共卫生负担方面具有巨大潜力。