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

基本信息

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
项目类别：
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

项目摘要

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，但针对疾病特异性损伤的干预措施却很少。ASD 的复杂性和异质性表明，针对多个领域的干预措施更有可能具有治疗作用。这项以患者为导向的研究职业发展奖支持候选人的长期目标，即针对自闭症谱系障碍的核心症状建立有效的干预措施，并有能力整合行为干预和药物发现研究中快速发展的发现。项目和监督活动将侧重于获得自闭症谱系障碍表型多样性背后的分子和神经机制方面的专业知识，探究联合疗法的活性成分，并研究行为和药物治疗背后的机制。该奖项将设在拉什大学医学中心。在伊利诺伊大学芝加哥分校的 Mark Pollack 博士以及 Ed Cook、Luan Phan 和 Don Hedeker 博士的指导下，并得到了包括 Connie Kasari 博士在内的国家专家的咨询。（加州大学洛杉矶分校）、Linmarie Sikich（北卡罗来纳大学教堂山分校）和 Kevin Pelphrey（耶鲁大学医学院）该候选人的当前重点是研究一种针对高阶社交的新型行为药理学疗法。该研究计划提出了一种概念验证的组合干预措施，旨在解决可能影响患有自闭症谱系障碍的学龄儿童的社会学习的个人治疗目标。申请人针对自闭症谱系障碍青少年的非语言交流、情绪识别和心理理论缺陷进行的有针对性的认知行为干预（CBI）的随机、比较试验我们将评估联合使用神经肽催产素（OT）的安全性、耐受性和有效性。该研究计划将患有自闭症谱系障碍 (ASD) 的 8-11 岁青少年随机分为 12 节、随机、平行的 CBI+OT 小组设计或控制社会群体条件（促进游戏），在 CBI 群体活动之前进行有针对性的鼻内 OT 给药将有助于增强群体和家庭作业活动期间的社会认知，促进目标技能的行为排练，并产生行为和行为方面的变化。该研究计划将与导师团队合作，研究从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中得出的候选任务组。用于细化治疗目标并确定潜在的社会认知机制，通过组合的社会认知干预来预测治疗反应。