Prevention Trial of Family Focused Treatment in Youth at Risk for Psychosis

描述(由申请人提供)：本申请涉及广泛的挑战领域4(临床研究)和特定挑战主题04-MH-105(为成人过渡制定干预和服务提供模式)。我们研究的目标是进行一项四个地点(加州大学洛杉矶分校、埃默里大学、北卡罗来纳州、耶鲁大学)的试点随机试验(N=96)，以确定为期6个月的家庭重点治疗(FFT)与常规治疗(TAU)在改善功能结果、稳定症状以及预防或延迟12-25岁符合前驱综合征(SIPS)前驱风险综合征标准的青年中完全精神病发作方面的有效性。我们的第一、第二和第三假设分别是，高危先证者在6个月和12个月的随访中，在(1)学校和社会功能、家庭功能和父母痛苦、(2)症状轨迹(SIPS评分)和(3)首次完全精神病发作的时间方面，对FFT的反应比TAU更好。受试者将从目前资助的一项前瞻性纵向研究(北美前驱纵向研究，简称NAPLS)的参与者中挑选出来，该研究阐明了转化为精神病的预测因素和机制，这四个网站在这项研究上进行了合作。受试者将在两年内每6个月接受一次访谈，以评估阳性和阴性症状、学业和社会功能、家庭功能以及向精神病的转化。我们建议的一个主要好处是，招募和临床评估的费用将由NAPLS补助金承担，这使得挑战补助金的资源可以集中在执行拟议的治疗研究上。风险确定方法的最新进展使人们能够可靠地识别出有前驱症状或“临床高风险”综合征的人，其中35%的人在两年半内发展为精神病。这一范例为在完全精神病发作和大量功能残疾积累之前的前驱阶段开发和测试干预措施提供了机会。心理社会干预似乎非常适合于解决精神病前驱症状中的动机缺陷和功能残疾问题。鉴于我们目前对精神病发病机制的认识状况，以及先兆患者抗精神病药物的初步研究在预防方面产生了令人沮丧的结果，在短期内，减少功能性残疾可能比减少精神病发病率更容易实现。我们已经开发并试行了针对前驱青少年的FFT(FFT-PY)，包括心理教育、沟通培训和解决问题的技能培训。在随机试验中，与接受简单心理教育控制条件的患者相比，接受FFT治疗的双相情感障碍成人和青少年以及有双相情感障碍风险的儿童在症状和功能上都有所改善。此外，一项针对精神病高危青少年的家庭心理教育的公开试验显示，相对于基线分数，症状和功能都有所改善。然而，还没有随机对照研究检验FFT在减少功能残疾和防止功能恶化或完全精神病的发作方面的有效性。鉴于对心血管疾病、糖尿病和某些形式的癌症采取预防措施后生活质量的提高和护理费用的降低，精神病学领域需要对其最令人衰弱的症状--精神障碍--的早期发现/预防框架作出重大承诺。前驱风险综合征标准已经导致了在预测完全精神病的发生方面高度有效的临床算法。然而，如果我们缺乏在发病前阶段进行干预的手段，以减少发展为完全精神病的可能性，或者减少功能性残疾的积累，或者两者兼而有之，那么这种知识的作用将是有限的。目前还没有经济有效的、基于证据的心理社会方法来预防精神病。在这些疾病成为慢性病之前，预防早期发作的神经毒性影响，并将早期发作的心理社会后遗症降至最低，可能会在很大程度上预防精神病造成的长期残疾，从而对公共健康产生重大影响。我们的研究将采取关键的下一步，对非常有希望的以家庭为重点的干预措施进行初步疗效测试，旨在稳定症状并改善高危青少年的社会和角色功能。 公共卫生相关性：预防精神分裂症等精神疾病和相关的功能残疾可以减轻个人和家庭痛苦的巨大负担以及对社会的经济损失。这一4个站点的项目旨在进行一项试验性随机试验，以确定以家庭为重点的治疗与常规治疗相比在改善功能结果、稳定症状以及预防或推迟具有前驱症状的过渡年龄青年完全精神病发作方面的有效性。这项研究的结果将对开发具有成本效益的、以证据为基础的心理社会方法预防精神病至关重要，因此将对公共卫生产生重大影响。

DESCRIPTION (provided by applicant): This application addresses Broad Challenge Area 4 (Clinical Research) and Specific Challenge Topic 04- MH-105 (Developing interventions and service delivery models for the transition to adulthood). The goal of our research is to conduct a four-site (UCLA, Emory, North Carolina, Yale) pilot randomized trial (N = 96), to determine the efficacy of a 6-month Family-Focused Treatment (FFT) in comparison with Treatment-As-Usual (TAU) in enhancing functional outcomes, stabilizing symptoms, and preventing or delaying the onset of full psychosis in youth aged 12-25 years who meet criteria for a prodromal risk syndrome according to the Structured Interview for Prodromal Syndromes (SIPS). Our primary, secondary, and tertiary hypotheses, respectively, are that at-risk probands will respond better to FFT than TAU at 6- and 12-month follow-ups, in terms of (1) school and social functioning, family functioning, and parental distress, (2) symptom trajectories (SIPS scores), and (3) time to first onset of full psychosis. Subjects will be drawn from the participants in a currently funded prospective, longitudinal study elucidating predictors and mechanisms of conversion to psychosis (North American Prodrome Longitudinal Study, or NAPLS), on which the four sites collaborate. Subjects will be interviewed every 6 months for 2 years to assess positive and negative symptoms, academic and social functioning, family functioning, and conversion to psychosis. A major advantage of our proposal is that the costs of recruitment and clinical evaluation will be borne by the NAPLS grant, which allows the resources of the Challenge Grant to be concentrated on performing the proposed Treatment Study. Recent progress in risk ascertainment methodology has enabled reliable identification of persons with prodromal or "clinical high-risk" syndromes, 35% of whom develop psychosis within 2 and 1/2 years. This paradigm provides an opportunity for developing and testing interventions in the prodromal phase, before the onset of full psychosis and accumulation of substantial functional disability. Psychosocial interventions appear to be well suited to address issues of motivational deficits and functional disability in the psychosis prodrome. Given our present state of knowledge regarding the mechanisms of psychosis onset, and given that initial studies of antipsychotic drugs in prodromal patients have produced discouraging results in terms of prevention, a reduction in functional disability may represent a more achievable target in the short term than a reduction in psychosis incidence. We have developed and piloted a version of FFT for prodromal youth (FFT-PY) consisting of psychoeducation, communication training, and problem-solving skills training. In randomized trials, adults and adolescents with bipolar disorder and children at-risk for bipolar disorder undergoing FFT improved symptomatically and functionally compared to patients in brief psychoeducational control conditions. Further, an open trial of family psychoeducation for youth at risk for psychosis demonstrated symptomatic and functional improvements relative to baseline scores. However, no randomized controlled study has examined the efficacy of FFT for reducing functional disability and preventing functional deterioration or onset of full psychosis. In view of the improvements in quality of life and the reductions in costs of care that have occurred with preventive approaches to cardiovascular disease, diabetes, and certain forms of cancer, the field of psychiatry is in need of a major commitment to an early detection/prevention framework for its most debilitating syndromes - the psychotic disorders. The prodromal risk syndrome criteria have resulted in clinical algorithms that are highly effective in predicting onset of full psychosis. However, such knowledge will be of limited utility if we lack the means of intervening in the pre-onset phase in a way that either reduces the likelihood of progression to full psychosis, the accumulation of functional disability, or both. There are currently no cost- effective, evidence-based psychosocial approaches to psychosis prevention. Preventing the neurotoxic effects of early episodes, before these illnesses become chronic, and minimizing the psychosocial sequelae of early episodes, may do much to prevent the long-term disability caused by psychosis and thereby have a major impact on public health. Our study will take the critical next step by performing an initial efficacy test of a highly promising family-focused intervention designed to stabilize symptoms and improve social and role functioning in at risk youth. PUBLIC HEALTH RELEVANCE: Preventing psychotic disorders such as schizophrenia and associated functional disability could relieve an enormous burden of personal and family suffering and economic losses to society. This 4-site project aims to conduct a pilot randomized trial to determine the efficacy of a family-focused treatment in comparison with treatment-as-usual in enhancing functional outcomes, stabilizing symptoms, and preventing or delaying the onset of full psychosis in transitional age youth with prodromal symptoms. The results of this study will be crucial for the development of cost-effective, evidence-based psychosocial approaches to psychosis prevention and thus will have major implications for public health.