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: 8939951
• 负责人: Susan Swedo
• 金额: $ 82.76万
• 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/8939951
• 关键词: Acute; Adolescent; Adverse effects; Affect; Aggressive behavior; Animal Model; Antibiotic Prophylaxis; Antibodies; Antigens; Anxiety; Autoimmune Process; Award; Behavior; Behavioral; Biological; Biological Markers; Cell Wall; Child; Childhood; Clinical; Comorbidity; Data; Deterioration; Development; Disease; Distress; Double-Blind Method; Eating Disorders; Emotional; Enrollment; Enuresis; Etiology; Evaluation; Funding; Goals; Health Sciences; Hour; Impairment; Increased frequency of micturition; Individual; Infection; Infusion procedures; Intravenous Immunoglobulins; Investigation; Joints; Laboratories; Mental Depression; Motor; National Institute of Mental Health; Obsession; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Oklahoma; Participant; Pathologic; Patients; Performance; Personality; Pharyngeal structure; Placebos; Plasmapheresis; Prevention; Production; Protocols documentation; Randomized; Research; Research Project Grants; Role; Rosa; Sampling; Scarlet Fever; Schools; Sensory; Separation Anxiety; Severities; Signs and Symptoms; Site; Sleep disturbances; Streptococcal Infections; Streptococcus pyogenes; Subgroup; Sydenham Chorea; Symptoms; Syndrome; Therapeutic Intervention; Thinking; United States National Institutes of Health; Universities; acronyms; base; bench to bedside; brain tissue; cohort; double-blind placebo controlled trial; experience; follow-up; micturition urgency; neuropsychiatry; novel; open label; 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. A unique subgroup of children with OCD has been identified on the basis of the acuity of their symptom onset. The cohort is identified by the acronym PANS, for Pediatric Acute-onset Neuropsychiatric Syndrome. The syndrome is characterized by the foudroyant onset of OCD and/or eating disorder, accompanied by at least two of the following seven comorbidities: 1) Anxiety; 2) Emotional lability and/or depression; 3) Irritability, aggression and/or severely oppositional behaviors; 4) Behavioral (developmental) regression; 5) Deterioration in school performance; 6) Sensory or motor abnormalities; 7) Somatic signs and symptoms, including sleep disturbances, enuresis or urinary frequency and others. For full description, see: Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut 2012, 2:2 http://dx.doi.org/10.4172/2161-0665.1000113 The clinical description of PANS arose from investigations of a group of children with acute-onset OCD whose symptoms appeared to arise as a consequence of common childhood infections, including Group A streptococcal (GAS) infections ("strep throat" and Scarlet fever). Children whose symptoms begin or exacerbate following GAS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The postulated etiology for the PANDAS subgroup is that specific strains of Group A streptococci (GAS), in genetically susceptible individuals, elicit the production of cross-reactive antibodies which recognize antigens not only on the GAS 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. Research at NIH and elsewhere has revealed 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; passive transfer of the cross-reactive antibodies replicated disease symptoms in animal models; 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 may produce 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. Dr. Swedo, Dr. James Leckman and colleagues at the Yale University Child Study Center, and Dr. Madeleine Cunningham of the University of Oklahoma Health Sciences Center were the joint recipients of an NIH "Bench to Bedside" award which helped fund a multi-site placebo-controlled trial of intravenous immunoglobulin (IVIG) for severely ill children with PANDAS (Protocol 11-M-0058, NCT 01281969) More than 40 children (3-12 yrs old) will be enrolled in the trial and 35 were randomly assigned to receive an infusion of IVIG or placebo. Long-term follow-up of the participants is ongoing, but data are available from baseline, 6 weeks, 3 months and 6 months evaluations. The double-blind and open-label results are being analyzed to evaluate changes in severity of OCD and related symptoms, overall functioning and adverse effects. In addition to providing information about the utility of IVIG treatment for PANDAS, the trial provided biological samples to be analyzed by Dr. Cunningham, Dr. Kyle Williams (MGH-Harvard), Dr. Mady Hornig (Columbia University) and Dr. Carlos Pardo (Johns Hopkins), 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. More information about the study is available at: http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2011-M-0058.html

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。 根据症状发作的敏锐度，已经确定了OCD儿童的独特子组。 该队列由小儿急性急性神经精神综合症的首字母pans鉴定。 该综合征的特征是强迫症和/或饮食失调的发作，并伴有以下七种合并症中的至少两种：1）焦虑； 2）情绪不稳定和/或抑郁； 3）烦躁，侵略和/或严重的对立行为； 4）行为（发展）回归； 5）学校表现恶化； 6）感觉或运动异常； 7）体征和症状，包括睡眠障碍，遗传或尿频等。 有关完整说明，请参见：Swedo SE，Leckman JF，Rose Nr。 从研究亚组到临床综合征：修改PANDAS标准以描述PANS（小儿急性发作神经精神综合症）。 Pediatr Therapeut 2012，2：2 http：//dx.doi.org/10.4172/2161-0665.1000113 潘斯的临床描述来自对一组急性发作强迫症的儿童的研究，其症状似乎是由于儿童常见感染而出现的，其中包括A组链球菌（气体）感染（“链球菌喉咙”和猩红热发烧）。气体感染后症状或加剧症状的儿童可能属于缩写旁pandas鉴定出的神经精神疾病的亚组（用于与链球菌感染相关的儿科自身免疫性神经精神疾病）。熊猫亚组的假定病因是，在遗传易感的个体中，A组链球菌（气体）的特定菌株引起了交叉反应性抗体的产生，这些抗体不仅在气体细胞壁上识别抗原，而且在宿主脑组织中也引起了宿主脑组织，引起了强迫症，强迫性，TICS，TICS，TICS，TICS，TICS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。 Research at NIH and elsewhere has revealed 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; passive transfer of the cross-reactive antibodies replicated disease动物模型中的症状；通过预防抗生素，预防神经精神症状的症状加剧；典型的“卧床”进展，并将临床观察和经验带入实验室，以寻找有关疗效机制的信息，因为跨反应性抗体鉴定了CNS中的抗原靶标的结果，这可能为治疗干预提供了新的靶标。 Dr. Swedo, Dr. James Leckman and colleagues at the Yale University Child Study Center, and Dr. Madeleine Cunningham of the University of Oklahoma Health Sciences Center were the joint recipients of an NIH "Bench to Bedside" award which helped fund a multi-site placebo-controlled trial of intravenous immunoglobulin (IVIG) for severely ill children with PANDAS (Protocol 11-M-0058, NCT 01281969）将招募40多名儿童（3-12岁），并随机分配35名儿童接受IVIG或安慰剂的注入。 参与者的长期随访正在进行中，但是可以从基线，6周，3个月零6个月的评估中获得数据。 正在分析双盲和开放标签的结果，以评估强迫症的严重程度和相关症状，整体功能和不良反应的变化。 除了提供有关IVIG治疗熊猫效用的信息外，该试验还提供了坎宁安博士，凯尔·威廉姆斯博士（MGH-HARVARD），MADY HORNIG（哥伦比亚大学）和Carlos Pardo博士和Carlos Pardo博士（Johns Hopkins）的生物样本，并进一步推广了跨性别的角色。活动和治疗反应。 有关该研究的更多信息，请访问：http：//clinicalstudies.info.nih.gov/cgi/detail.cgi?b_2011-m-0058.html