Integrated treatments for core deficits in autism spectrum disorder

自闭症谱系障碍核心缺陷的综合治疗

• 批准号: 9212010
• 负责人: LATHA Valluripalli SOORYA
• 金额: $ 14.68万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9212010
• 关键词: 11 year old; Academic Medical Centers; Address; Adolescent; Adverse effects; Affect; Affective; Aftercare; Age; Attention; Award; Base of the Brain; Behavior; Behavior Therapy; Behavioral; Biological; California; Chicago; Child; Childhood; Clinical; Cognition; Cognitive; Cognitive Therapy; Collaborations; Combined Modality Therapy; Complex; Consultations; Cycloserine; Data; Development; Disease; Dose; Educational Curriculum; Educational Intervention; Emotional; Emotions; Eye; Future; Glutamates; Goals; Heterogeneity; Human; Illinois; Impaired cognition; Impairment; Individual; Interpersonal Relations; Intervention; Intervention Studies; Investigation; Learning; Longevity; Los Angeles; Maintenance; Measurement; Measures; Mediating; Mediation; Memory; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentorship; Mind; Modality; Molecular; Neuropeptides; Neurosciences; Neurosecretory Systems; Noise; Nonverbal Communication; North Carolina; Outcome; Oxytocin; Pathogenicity; Pathway interactions; Perception; Peripheral; Pharmacological Treatment; Pharmacotherapy; Phenotype; Pilot Projects; Play; Prevalence; Process; Psyche structure; Quality of life; Randomized; Regulation; Research; Research Training; Role; Safety; School-Age Population; Signal Transduction; Social Behavior; Social Controls; Social support; Socialization; Supervision; Symptoms; System; Therapeutic; Training Programs; Treatment Efficacy; Treatment Factor; Treatment Protocols; United States; Universities; Youth; autism spectrum disorder; base; behavioral pharmacology; brain behavior; communication behavior; comparative trial; cooking; critical developmental period; design; disability; drug discovery; effective intervention; gamma-Aminobutyric Acid; group intervention; impression; improved; information processing; interest; life time cost; medical schools; mental state; neuromechanism; neuropsychiatric disorder; next generation; novel; predicting response; predictive of treatment response; psychosocial; public health relevance; rehearsal; skills; skills training; social; social cognition; social communication; social group; social learning; social skills; targeted treatment; theories; therapy design; treatment effect

 DESCRIPTION (provided by applicant): Despite progress in efficacious treatments for individuals with autism spectrum disorder (ASD), few interventions are available for disease-specific impairments. The complexity and heterogeneity of ASD suggests interventions targeting multiple domains are more likely to have a therapeutic impact. This Mentored Patient-Oriented Research Career Development Award supports the candidate's long-term goals of building effective interventions for core symptoms in ASD with capacity to integrate the rapidly evolving findings from both behavioral intervention and drug discovery research. The training program and supervised activities will focus on gaining expertise in the molecular and neural mechanisms underlying phenotypic diversity in ASD, interrogating active ingredients from combination therapies, and investigating mechanisms underlying both behavioral and pharmacological treatments. The award is will be based at the Rush University Medical Center under the mentorship of Dr. Mark Pollack and co-mentorship of Drs. Ed Cook, Luan Phan, and Don Hedeker at the University of Illinois-Chicago; and with consultation from national experts including Drs. Connie Kasari (University of California, Los Angeles), Linmarie Sikich (University of North Carolina-Chapel Hill), and Kevin Pelphrey (Yale School of Medicine). The candidate's immediate focus is to study a novel, behavioral- pharmacological therapy targeting higher-order social information processing impairments in youth with ASD. The research plan proposes a proof-of-concept, combination intervention designed to address individual treatment targets presumed to influence social learning in school aged children with ASD. This proposal builds upon data from the applicant's randomized, comparative trial of a targeted cognitive-behavioral intervention (CBI) for nonverbal communication, emotion recognition, and theory of mind deficits in youth with ASD. We will evaluate the safety, tolerability, and efficacy of combining the neuropeptide oxytocin (OT) with the targeted CBI group curriculum. The research plan will randomize 8-11 year old youth with ASDs (n=50), into a 12- session, randomized, parallel group design of CBI+OT or a control social group condition (facilitated play). It is hypothesized that targeted, intranasal OT dosing immediately prior to CBI group activities will serve enhance social cognition during group and homework activities, facilitate behavioral rehearsal of target skills, and yield changes in both behavioral and cognitive domains supporting social learning during childhood. In collaboration with the mentorship team, the research plan will investigate a candidate task battery drawing from neuroscience measurement strategies of brain-behavior relationships underlying social cognition and affective regulation. The candidate task battery will be used refine treatment targets and identify potential social cognitive mechanisms predicting treatment response from the combined social cognitive intervention.

 描述(由申请人提供)：尽管对自闭症谱系障碍(ASD)患者的有效治疗取得了进展，但针对特定疾病的损害的干预措施很少。ASD的复杂性和异质性表明，针对多个领域的干预更有可能产生治疗效果。这项以患者为导向的导师研究职业发展奖支持候选人的长期目标，即建立针对ASD核心症状的有效干预措施，并有能力整合来自行为干预和药物发现研究的快速演变的发现。培训计划和监督活动将侧重于获得ASD表型多样性潜在的分子和神经机制方面的专业知识，询问联合治疗的有效成分，并调查行为和药物治疗的基础机制。该奖项将设在拉什大学医学中心，由Mark Pollack博士指导，伊利诺伊大学芝加哥分校Ed Cook、Luan Phan和Don Hedeker博士共同指导，并由包括康妮·卡萨里博士(加州大学洛杉矶分校)、Linmarie Sikich博士(北卡罗来纳大学教堂山分校)和Kevin Pelphrey博士(耶鲁医学院)等国家专家咨询。这位候选人的当务之急是研究一种新的行为药物疗法，针对患有自闭症的年轻人的高阶社会信息处理障碍。该研究计划提出了一种概念验证、联合干预措施，旨在解决被认为会影响自闭症学龄儿童社会学习的个别治疗目标。这项建议基于申请者对患有自闭症的青少年进行的有针对性的认知-行为干预(CBI)的随机对照试验的数据，该干预针对患有自闭症的青少年的非语言交流、情绪识别和心理缺陷理论。我们将评估将神经肽催产素(OT)与目标CBI组课程相结合的安全性、耐受性和有效性。该研究计划将患有自闭症的8-11岁青少年(n=50)随机分成CBI+OT或对照社会团体条件(促进游戏)的12个疗程的随机平行小组设计。有人假设，在CBI小组活动之前立即进行有针对性的鼻内注射OT将有助于在小组和家庭作业活动中增强社会认知，促进目标技能的行为排练，并在支持儿童时期社会学习的行为和认知领域产生变化。在与导师团队的合作下，该研究计划将从神经科学测量策略中提取社会认知和情感调节背后的大脑-行为关系的神经科学测量策略，以调查候选任务组。候选任务组将 用于细化治疗目标，并确定潜在的社会认知机制，预测综合社会认知干预的治疗反应。