Evaluation and Treatment of Obsessive Compulsive and Related Disorders

强迫症及相关疾病的评估和治疗

• 批准号: 7969320
• 负责人: Susan Swedo
• 金额: $ 20.09万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7969320
• 关键词: Acute; Adolescent; Age; Antibiotic Prophylaxis; Antibodies; Antigens; Autoimmune Process; Basal Ganglia; Biological Assay; Cell Wall; Characteristics; Child; Childhood; Clinical; Clinical Trials; Collaborations; Data Analyses; Disease; Enrollment; Etiology; Evaluation; Excitatory Amino Acid Antagonists; Florida; Functional disorder; Glycoproteins; Goals; Hour; Individual; Infection; Intramural Research Program; Intravenous Immunoglobulins; Laboratories; Learning; Longitudinal Studies; Mus; National Institute of Mental Health; Neurologic Symptoms; Observational Study; Obsession; Obsessive-Compulsive Disorder; Oklahoma; Paper; Pharmaceutical Preparations; Placebos; Plasmapheresis; Prevention; Production; Psychiatry; Public Health; Publications; Reporting; Research; Research Project Grants; Riluzole; Sampling; Serum; Severities; Streptococcal Infections; Subgroup; Sydenham Chorea; Symptoms; Therapeutic Intervention; Tic disorder; Time; Writing; acronyms; bench to bedside; brain tissue; cohort; double-blind placebo controlled trial; experience; interest; neuropsychiatry; novel; research clinical testing; response

There are two projects within this research portfolio. The first is a longitudinal study of children in the PANDAS subgroup (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) and the second is a clinical trial of riluzole - a glutamate antagonist with some preliminary evidence of benefit for children and adolescents with obsessive-compulsive disorder (OCD). A double-blind, placebo-controlled trial of riluzole is currently underway for children ages 7 - 17 years. During the reporting period, the mid-point of the study was reached and an interim data analysis revealed encouraging, but not yet significant, results. Further analyses revealed that the full cohort of 60 children will be required to reach statistical significance. Therefore, enrollment is ongoing and interested individuals are invited to learn more about the study at: http://clinicalstudies.info.nih.gov/detail/A_2005-M-0225.html In some cases, childhood-onset OCD and tic disorders appear to arise as sequelae of common childhood infections, including Group A beta-hemolytic streptococcal (GABHS) infections. Children whose symptoms begin or exacerbate following GABHS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The PANDAS subgroup shares several common clinical characteristics and may share a common pathophysiology for their symptoms. The postulated etiology for the PANDAS subgroup is that specific strains of GABHS, in genetically susceptible individuals, elicit the production of cross-reactive antibodies which recognize antigens not only on the strep. cell wall, but also in the host brain tissue, eliciting obsessions, compulsions, tics and other neuropsychiatric symptoms. The cross-reactive antibodies have been shown to correlate with other anti-streptococcal antibodies and also with neuropsychiatric symptom severity, with highest titers seen in children acutely ill with Sydenham chorea or PANDAS symptomatology. A recent report by Yaddanapudi et al (Mol Psychiatry advance on-line publication, 11 Aug 2009; doi10.1038/mp.2009.77)demonstrated that passive transfer of these cross-reactive antibodies resulted in stereotypies and other neurologic symptoms in the recipient mice. This paper adds to the results of more than 15 years of research at the NIMH intramural program and elsewhere, demonstrating that: the PANDAS subgroup has a specific and identifiable symptom course (marked most notably by the acute, abrupt, overnight onset of symptoms ("zero to sixty in less than 24 hours"); the cross-reactive antibodies correlate with both GABHS infection status and neuropsychiatric symptom severity; prevention of GABHS infections through antibiotic prophylaxis results in prevention of neuropsychiatric symptom exacerbations; and, treatment of acutely ill children with immunomodulatory therapies (specifically, intravenous immunoglobulin (IVIG)or plasmapheresis) results in dramatic reductions in symptom severity. This line of research is unusual, in that it reversed the typical "bench to bedside" progression and took clinical observations and experiences into the laboratory in search of information about etiopathogenic mechanisms. The results proved exciting, as the cross-reactive antibodies identified antigenic targets in the CNS which provide new targets for therapeutic interventions. If novel therapies can be developed, it will have a tremendous public health impact, as 1 in 150 children suffers from OCD and many do not benefit from currently available treatments. During this reporting period, the Branch's research on PANDAS has focused on determining the temporal relationship between streptococcal infections and symptom onset and exacerbations. Children with recent-onset OCD were followed prospectively for up to two years, with clinical evaluations and serial serum samples. The temporal relationship between symptom exacerbations and streptococcal infections is being examined to determine whether or not membership in the PANDAS subgroup can be predicted at initial presentation. Final data analyses are being completed at the time of this writing, in collaboration with Dr. Tanya Murphy at Univ of South Florida. In addition, the samples from children with a PANDAS symptom course will be sent to Dr. Madeleine Cunningham (Univ Oklahoma) and Dr. Christie Kirvan (UC-Davis) for cross-reactive antibodies assays.

该研究组合中有两个项目。 第一个是对熊猫亚组儿童的纵向研究（儿科自身免疫性神经精神疾病与链球菌感染相关），第二个是瑞鲁唑的临床试验 - 谷氨酸拮抗剂，具有一些对患有compastive compessive compessive compessive compessive -compersive compessive compessive -compersive -comptiment -comptiment -comptiment -comptiment -comptiment -comptiment -comptimentimentiment的拮抗剂。 Riluzole的双盲，安慰剂对照试验目前正在为7至17岁的儿童进行。 在报告期间，达到了研究的中点，并且临时数据分析显示令人鼓舞但尚不显着的结果。 进一步的分析表明，将需要60名儿童的全部队列才能达到统计意义。 因此，招生正在进行，并邀请感兴趣的人在以下网址了解有关该研究的更多信息： 在某些情况下，儿童期强迫症和抽动疾病似乎是常见儿童感染的后遗症，包括A组β-溶血性链球菌（GABHS）感染。 GABHS感染后症状开始或恶化的儿童可能属于由phonym pandas鉴定出的神经精神疾病的亚组（对于与链球菌感染相关的儿科自身免疫性神经精神疾病）。大熊猫亚组具有几种常见的临床特征，并且可能会出现常见的病理生理学症状。 熊猫亚组的假定病因是，在遗传易感的个体中，gabhs的特定菌株引起了交叉反应性抗体的产生，这些抗体不仅识别链球菌上的抗原。细胞壁，但还在宿主脑组织中，引起痴迷，强迫，抽动和其他神经精神症状。 交叉反应性抗体已显示出与其他抗链球菌抗体以及神经精神症状的严重程度相关的，并且儿童在儿童中与Sydenham Chorea或Pandas症状急性病。 Yaddanapudi等人的最新报告（Mol Psychiatry在线出版，2009年8月11日； DOI10.1038/MP.2009.77）表明，这些交叉反应性抗体的被动转移导致刻板印象和其他受体小鼠中的其他神经学症状。 本文增加了在NIMH壁内计划和其他地方进行15年研究的结果，这表明：熊猫亚组具有特定且可识别的症状课程（最明显的是急性，突然突然的，过夜的症状发作（“在不到24小时内零至60个零至60个相关的抗体状态”；通过预防抗生素的预防，导致神经精神病的症状加剧；典型的“长椅”的进展，并将临床观察和经验带入实验室，以寻找有关疗法机制的信息，因为交叉反应抗体确定了CNS中的抗原靶标的结果。 如果可以开发出新的疗法，它将产生巨大的公共卫生影响，因为150名儿童患有强迫症，许多儿童中有1人无法从目前可用的治疗中受益。 在此报告期间，该分支机构对大熊猫的研究集中在确定链球菌感染与症状发作和加剧之间的时间关系。近期发作强迫症的儿童被前瞻性遵循长达两年，并进行临床评估和系列血清样本。 正在检查症状加剧与链球菌感染之间的时间关系，以确定在初次呈现时是否可以预测熊猫亚组中的成员资格。 在撰写本文时，正在完成最终数据分析，并与南佛罗里达大学的Tanya Murphy博士合作。 此外，患有大熊猫症状课程的儿童的样本将发送给Madeleine Cunningham博士（Univ Oklahoma）和Christie Kirvan博士（UC-DAVIS）进行交叉反应性抗体分析。