Neuroimaging and Behavioral Biomarkers for ADHD in Children

儿童多动症的神经影像和行为生物标志物

• 批准号: 7941777
• 负责人: MARTIN H TEICHER
• 金额: $ 50万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941777
• 关键词: 12 year old; 17 year old; Address; Adult; Affect; Age; Area; Arts; Attention deficit hyperactivity disorder; Behavior Disorders; Behavioral; Biological Markers; Bipolar Disorder; Child; Childhood; Circadian Dysregulation; Circadian Rhythms; Clinical; DSM-IV; Data; Diagnosis; Disease; Functional disorder; Gender; Genetic Predisposition to Disease; Grant; Grouping; Hand; Head Movements; Hyperactive behavior; Impairment; Individual; Lead; Left; Measures; Mental disorders; Methylphenidate; Mood Disorders; Periodicity; Prefrontal Cortex; Prevalence; Process; Recording of previous events; Relaxation; Research; Sampling; Schools; Sensitivity and Specificity; Sleep; Symptoms; Testing; Time; Validation; actigraphy; aged; boys; childhood bipolar disorder; design; disorder control; disorder subtype; girls; male; meetings; neuroimaging; putamen; 12 year old; 17 year old; Address; Adult; Affect; Age; Area; Arts; Attention deficit hyperactivity disorder; Behavior Disorders; Behavioral; Biological Markers; Bipolar Disorder; Child; Childhood; Circadian Dysregulation; Circadian Rhythms; Clinical; DSM-IV; Data; Diagnosis; Disease; Functional disorder; Gender; Genetic Predisposition to Disease; Grant; Grouping; Hand; Head Movements; Hyperactive behavior; Impairment; Individual; Lead; Left; Measures; Mental disorders; Methylphenidate; Mood Disorders; Periodicity; Prefrontal Cortex; Prevalence; Process; Recording of previous events; Relaxation; Research; Sampling; Schools; Sensitivity and Specificity; Sleep; Symptoms; Testing; Time; Validation; actigraphy; aged; boys; childhood bipolar disorder; design; disorder control; disorder subtype; girls; male; meetings; neuroimaging; putamen

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area 03: Biomarker Discovery and Validation, and the specific Challenge Topic 03-MH-101: Biomarkers in Mental Disorders. Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent behavioral disorder of childhood affecting about 6 million school children and perhaps 10 million adults in the US. ADHD is however a very controversial disorder. Some critics question its validity, others argue that the criteria are too broad, too subjective, or not developmentally sensitive. Pediatric bipolar disorder is an even more controversial diagnosis, associated with widespread disparity between experts in criteria and prevalence rates. The aim of this Challenge Grant is to rigorously test our preliminary findings identifying three potential biomarkers. Two of these appear to be markers for ADHD that had perfect accuracy in discriminating between children with ADHD and controls in limited samples. However, these studies only included boys aged 9 - 12 who met criteria for Combined Subtype, and had been previously treated with methylphenidate (MPH). It is critical to ascertain if these findings can be replicated in an independent sample, extended to girls, older and younger individuals, to all ADHD subtypes, and to ADHD subjects with no prior history of psychotropic treatment. The third marker appears to identify children with bipolar disorder, and in a sample of 103 subjects distinguished bipolar from ADHD and controls with 94% sensitivity and specificity. Bipolar children in this sample met strict operational criteria for DSM-IV bipolar disorder. Hence, we propose to rigorously evaluate three potential biomarkers that address two severe but overlapping challenges. On one hand, there is the challenge of identifying where normal ends and where ADHD begins. On the other hand, there is the challenge of determining whether hyperactive, disruptive, aggressive and emotionally labile children have ADHD, bipolar disorder, both, or something entirely different. The first biomarker emerged from a state-of-the-art non-linear analysis of head movements and positional stability. The maximum Lyapunov exponent discriminated 62 ADHD children from 62 matched controls with perfect accuracy (ROC = 1.0). The second marker is a measure of regional T2-relaxation time (T2RT) in left putamen and right dorsolateral prefrontal cortex. The third marker is a composite of actigraph measures of sleep, daytime hyperactivity and circadian dysregulation. Children with DSM-IV bipolar disorder had greater impairments in sleep and circadian rhythmicity than children with ADHD and comorbid mood disorders. The validity of these potential markers will be tested in a mixed gender sample of 160 children (80 ADHD, 40 bipolar, 40 control) between 6-17 years of age (n=80 neuroimaging). Identifying markers that distinguish ADHD from normal and ADHD from bipolar could have an enormous impact on the field. These findings (if further validated) can lead to a revamping of clinical criteria, and rapidly advance research into the genetics, etiology, pathophysiology and treatment of ADHD and pediatric bipolar disorder. This Challenge Grant is designed to test the validity of two potential biomarkers that in preliminary studies distinguished boys with Attention-Deficit Hyperactivity Disorder (ADHD) from controls with complete accuracy. A third biomarker will also be studied that distinguished children with bipolar disorder from subjects with ADHD and healthy normal controls with 94% sensitivity and specificity. These markers will be assessed in 160 children (6-17 years of age) from both genders. Eighty subjects will have ADHD, 40 bipolar disorder, and 40 will be healthy controls.

描述（由申请人提供）：此申请应解决广泛的挑战领域03：生物标志物发现和验证以及具体挑战主题03-MH-101：精神障碍的生物标志物。注意力缺陷/多动症（ADHD）是最普遍的儿童行为障碍，影响了约600万学童，在美国也许是1000万成年人。但是，多动症是一种非常有争议的障碍。一些批评家质疑其有效性，另一些批评者认为，标准过于广泛，太主观或对发展敏感。小儿双相情感障碍是一个更具争议性的诊断，与专家在标准和患病率方面的广泛差异有关。这项挑战的目的是严格测试我们的初步发现，以识别三个潜在的生物标志物。其中两个似乎是多动症的标记，它们在有限的样本中区分患有ADHD的儿童和对照的儿童具有完美的准确性。但是，这些研究仅包括符合亚型合并标准的9-1岁的男孩，并且先前已用哌醋甲酯（MPH）治疗。至关重要的是，确定这些发现是否可以在独立的样本中复制，扩展到年龄较大和年轻人，所有多动症亚型，以及没有精神治疗史的ADHD受试者。第三个标记似乎可以鉴定患有双相情感障碍的儿童，并且在103名受试者的样本中，将双相情感障碍区分开，并且具有94％敏感性和特异性的对照。该样品中的双相儿童符合DSM-IV双相情感障碍的严格操作标准。因此，我们建议严格评估三种潜在的生物标志物，以解决两个严重但重叠的挑战。一方面，识别正常末端以及多动症开始的何处存在挑战。另一方面，要确定过度活跃，破坏性，侵略性和情绪不足的孩子患有多动症，双相情感障碍或完全不同的挑战。第一个生物标志物来自对头部运动和位置稳定性的最先进的非线性分析。最大Lyapunov指数将62名ADHD儿童与62个匹配的对照区分开（ROC = 1.0）。第二个标记是左壳和右侧前外侧前额叶皮层中区域T2 - 释放时间（T2RT）的度量。第三个标记是睡眠，白天多动症和昼夜节律失调的综合综合。 DSM-IV躁郁症患者的睡眠和昼夜节律障碍的损害比患有多动症和合并情绪障碍的儿童更大。这些潜在标记的有效性将在60岁的160名儿童（80 ADHD，40双（40双极，40个对照））的混合性别样本中进行测试（n = 80神经影像学）。识别将ADHD与正常和ADHD与双极性区分开的标记可能会对现场产生巨大影响。这些发现（如果得到进一步验证）可以导致临床标准的修改，并迅速提高对ADHD和小儿双相情感障碍的遗传学，病因，病理生理学和治疗的研究。这项挑战赠款旨在测试两个潜在的生物标志物的有效性，这些生物标志物在初步研究中，将注意力缺陷多动障碍（ADHD）与具有完全准确的对照组相称。还将研究第三个生物标志物，使患有躁郁症的儿童与ADHD和健康的正常对照受试者具有94％的敏感性和特异性。这些标记将在两个性别的160名儿童（6-17岁）中评估。 80名受试者将患有ADHD，40个双相情感障碍和40个受试者将是健康的对照。