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 1-2% 的儿童和青少年，持续不断的强迫思想和强迫行为会造成严重的痛苦和损害。 在某些情况下，儿童期发病的强迫症似乎是由常见的儿童感染引起的，包括 A 组 β 溶血性链球菌 (GABHS) 感染（“链球菌性咽喉炎”和猩红热）。感染 GABHS 后症状开始或加重的儿童可能属于神经精神疾病亚组，缩写为 PANDAS（与链球菌感染相关的儿童自身免疫性神经精神疾病）。 PANDAS 亚组具有一些共同的临床特征，并且其症状可能具有共同的病理生理学特征。 PANDAS 亚群的假设病因是 A 组 β 溶血性链球菌 (GABHS) 的特定菌株在遗传易感个体中引发交叉反应抗体的产生，这些抗体不仅识别 GABHS 细胞壁上的抗原，而且识别宿主脑组织中的抗原，从而引起强迫症、强迫症、抽动和其他神经精神症状。 交叉反应抗体已被证明与其他抗链球菌抗体以及神经精神症状严重程度相关，在患有 Sydenham 舞蹈病或 PANDAS 症状的急性儿童中观察到最高滴度。 Yaddanapudi 等人最近的一份报告（Mol Psychiatry advance 在线出版物，2009 年 8 月 11 日；doi10.1038/mp.2009.77）证明，这些交叉反应抗体的被动转移导致受体小鼠出现刻板印象和其他神经系统症状。 本文补充了 NIMH 校内计划和其他地方超过 15 年的研究结果，证明：PANDAS 亚群具有特定且可识别的症状过程（最显着的是急性、突然、夜间症状发作（“不到 24 小时内从零到六十”）；交叉反应抗体与 GABHS 感染状态和神经精神症状相关 严重程度；通过抗生素预防预防 GABHS 感染可预防神经精神症状恶化；通过免疫调节疗法（特别是静脉注射免疫球蛋白 IVIG 或血浆置换术）治疗急性病儿童可显着减轻症状严重程度。 这条研究路线很不寻常，因为它颠覆了典型的研究方向 “从实验室到临床”的进展，并将临床观察和经验带入实验室，以寻找有关病因病理机制的信息。 结果令人兴奋，因为交叉反应抗体识别出中枢神经系统中的抗原靶点，这可能为治疗干预提供新的靶点。 PANDAS 研究代表了该分支（Swedo 博士）与耶鲁大学儿童研究中心的 James Leckman 博士及其同事以及俄克拉荷马大学健康科学中心的 Madeleine Cunningham 博士之间的合作关系。 博士。 Swedo、Leckman 和 Cunningham 共同获得了 NIH“从实验室到床边”奖，该奖项正在帮助资助针对患有 PANDAS 的重症儿童进行静脉注射免疫球蛋白 (IVIG) 的多中心安慰剂对照试验。 最多 50 名儿童（3-12 岁）将参加试验，并随机分配接受 IVIG 或安慰剂输注。 除了提供有关 IVIG 治疗 PANDAS 效用的信息外，该试验还将生成供 Cunningham 博士和其他人分析的生物样本，目的是进一步描述交叉反应抗体的病理作用，并有可能开发疾病活动和治疗反应的生物标志物。该试验目前正在招募受试者。筛查由耶鲁大学和 NIH 的团队完成，但所有临床互动均在 NIH 临床中心进行。有关该研究的更多信息，请访问：http://clinicaltrials.gov/ct2/show/NCT01281969?term=bethesda%2C+MD+%2B+PANDAS&rank=1