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: 8342113
• 负责人: Susan Swedo
• 金额: $ 52.95万
• 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/8342113
• 关键词: Acute; Adolescent; Affect; Annual Reports; Antibiotic Prophylaxis; Antibodies; Antigens; Autoimmune Process; Award; Biological; Biological Markers; Cell Wall; Characteristics; Child; Childhood; Clinical; Disease; Distress; Emotional; Enrollment; Enuresis; Etiology; Evaluation; Functional disorder; Funding; Goals; Health Sciences; Hour; Impairment; Individual; Infection; Infusion procedures; Institution; Institutional Review Boards; Intramural Research Program; Intravenous Immunoglobulins; Joints; Laboratories; Mus; National Institute of Mental Health; Neurologic Symptoms; Obsession; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Oklahoma; Paper; Pathologic; Patients; Personality; Pharyngeal structure; Placebos; Plasmapheresis; Prevention; Production; Psychiatry; Publications; Randomized; Reporting; Research; Research Project Grants; Role; Safety; Sampling; Scarlet Fever; Screening procedure; Separation Anxiety; Severities; Site; Streptococcal Infections; Subgroup; Sydenham Chorea; Symptoms; Therapeutic Intervention; Thinking; United States National Institutes of Health; Universities; acronyms; bench to bedside; brain tissue; clinical efficacy; cohort; experience; micturition urgency; neuropsychiatry; novel; placebo controlled study; treatment response

Obsessive-compulsive disorder (OCD) affects 1-2% of children and adolescents, causing significant distress and impairments from the unrelenting obsessional thoughts and compulsive behaviors. In some cases, childhood-onset OCD appears to arise as a consequence of common childhood infections, including Group A beta-hemolytic streptococcal (GABHS) infections ("strep throat" and Scarlet fever). 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 group A beta hemolytic streptococi (GABHS), in genetically susceptible individuals, elicit the production of cross-reactive antibodies which recognize antigens not only on the GABHS 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 IVIGor 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 might provide new targets for therapeutic interventions. The PANDAS research represents a collaborative relationship among this branch (Dr. Swedo) and Dr. James Leckman and colleagues at the Yale University Child Study Center and Dr. Madeleine Cunningham of the University of Oklahoma Health Sciences Center. Drs. Swedo, Leckman, and Cunningham were the joint recipients of an NIH "Bench to Bedside" award which is helping to fund a multi-site placebo-controlled trial of intravenous immunoglobulin (IVIG) for severely ill children with PANDAS. Up to 50 children (3-12 yrs old) willl be enrolled in the trial and randomly assigned to receive an infusion of IVIG or placebo. In addition to the information provided about the utility of IVIG treatment for PANDAS, the trial will generate biological samples to be analyzed by Dr. Cunningham and others, with the goal of further delineating the pathologic role of the cross-reactive antibodies, as well as potentially developing biomarkers for disease activity and treatment response. The trial is currently enrolling subjects. Screening is done by teams at Yale and at NIH, but all clinical interactions take place at the NIH Clinical Center. More information about the study is available at: http://clinicaltrials.gov/ct2/show/NCT01281969?term=bethesda%2C+MD+%2B+PANDAS&rank=1

强迫症（OCD）影响了1-2％的儿童和青少年，从而造成了无情的痴迷思想和强迫行为的严重困扰和损害。 在某些情况下，儿童发作的OCD似乎是由于常见的儿童感染而引起的，包括A组β-溶血性链球菌（GABHS）感染（“链球菌喉咙”和Scarlet Fever）。 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，在遗传上易感的个体中，A组A组的特定菌株会引起交叉反应性抗体的产生，这些抗体识别抗原，这些抗原不仅在GABHS细胞壁上，而且在宿主脑组织中，而且在宿主脑组织中，而且在宿主的脑组织中，还具有症状，并具有强制性的症状，并具有其他症状。 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”；通过抗生素预防的防止GABHS导致神经精神症状的症状加剧； “床头”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，因为交叉反应性抗体确定了CNS中的抗原靶标，这可能为治疗干预提供了新的靶标。 熊猫研究代表了耶鲁大学儿童学习中心和俄克拉荷马大学健康科学中心的玛德琳·坎宁安博士的该分支机构（瑞典博士）和詹姆斯·莱克曼博士和同事之间的合作关系。 博士。 Swedo，Leckman和Cunningham是NIH“卧床床位”奖的共同获得者，该奖项正在帮助为严重患有PANDAS的严重患病儿童提供静脉内免疫球蛋白（IVIG）的多站点安慰剂对照试验。 最多有50名儿童（3-12岁）将参加试验，并随机分配接受IVIG或安慰剂的输注。 除了提供有关大熊猫的IVIG治疗效用的信息外，该试验还将生成坎宁安博士和其他人分析的生物样品，目的是进一步描述交叉反应性抗体的病理作用，以及潜在地发育的生物标志物来为疾病活动和治疗反应发展。该试验目前正在招募主题。筛查是由耶鲁大学和NIH的团队进行的，但所有临床相互作用均在NIH临床中心进行。有关该研究的更多信息，请访问以下网址：http：//clinicaltrials.gov/ct2/show/nct01281969?term = bethesda%2C+md+mmd+%%2B+pandas＆rank = 1