BIOCHEMICAL MECHANISMS UNDERLYING IMPAIRED ATTENTION

注意力受损的生物化学机制

• 批准号: 3084605
• 负责人: TIMOTHY P BOHAN
• 金额: $ 7.94万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084605
• 关键词: Tourette's syndrome; adult human (21+); attention; attention deficit disorder; bromocriptine; child (0-11); dopamine receptor; human subject; impulsive behavior; methylphenidate; pergolide; pimozide; psychological tests; psychomotor function; psychopharmacology; short term memory

This proposal addresses potential biochemical mechanisms underlying impaired attention in children. The primary objective is to study how the components of attention and related neurobehavioral processes are affected by drugs which activate either all Dopamine (DA) receptors, just D1 receptors, D2 and D3 receptors, or just D3 receptors. We propose to investigate various components of attention and related neurobehavioral processes using a systematic, multidimensional assessment in children and adults with impaired attention due to (a) attention deficit hyperactivity disorder (ADHD), or (b) Tourettes Syndrome with and without ADHD. Such populations provide a unique opportunity to address the question of whether impaired attention in children has a similar biochemical basis regardless of its etiology. We will investigate the effects of several different drugs including: a) methylphenidate, b) pimozide, c) bromocriptine and d) pergolide. Two specific aims each with their own set of hypotheses will be addressed. Specific Aim 1 (The nature of impaired attention) addresses the relationship between the etiology of the attentional problem and the pattern of attentional deficits. We will assess different components of attention including selective and sustained attention, disinhibition as well as short term memory and fine-motor skills. It is not clear how these factors vary with different etiologies of attentional impairment. The hypotheses that will be addressed are: 1) ADHD and TS/ADHD subjects will not differ in the degree to which particular attentional skills are impaired, but they will differ in the motor skills with both TS/ADHD and TS subjects having a greater impairment in motor skills. Specific Aim 2 (The Pharmacological Basis of Impaired Attention, Fine Motor Skills and Impulsivity) addresses the relationship between DA activators and alterations in specific cognitive and motor impairments. The hypotheses that will be addressed are: 1) impaired attention is reduced by activation of D1 receptors but not by activation of D2 and/or D3 receptors; 2) fine-motor skills are affected by activation of D2 receptors, but not by activation of D1 or D3 receptors; 3) impulsivity is reduced by activation of D3 receptors, but not by the activation of D1 and/or D2 receptors. These objectives will be analyzed with a detailed comprehensive multivariate analysis. There are no studies comparing the effect of selective activation of different dopamine receptors on the various components of impaired attention. There are also no studies comparing the effect of drugs in children with impaired attention due to varying etiologies.

这一建议解决了潜在的生化机制 儿童注意力受损。其主要目标是研究 注意力的组成部分和相关的神经行为过程会受到影响 通过药物激活所有的多巴胺(DA)受体，只激活D1 受体，D2和D3受体，或仅D3受体。我们建议 研究注意力的各种成分和相关的神经行为 在儿童和儿童中使用系统的、多方面的评估过程 因(A)注意力缺陷多动而注意力受损的成年人 多动症(ADHD)，或(B)伴或不伴ADHD的抽动症综合征。 这样的人口提供了一个独特的机会来解决 儿童注意力受损是否有相似的生化基础 不管它的病因如何。我们将调查几个因素的影响 不同的药物包括：a)哌醋甲酯，b)吡莫齐特，c) 溴隐亭和培高利特。两个明确的目标，每个目标都有自己的目标 一系列的假设将被解决。具体目标1(受损害的性质 注意)解决了以下原因之间的关系： 注意问题和注意缺陷的模式。我们会 评估注意力的不同组成部分，包括选择性和持续性 注意力、去抑制、短时记忆和精细运动 技能。目前尚不清楚这些因素如何随不同的病因而变化。 注意力障碍。将讨论的假设如下：1) ADHD和TS/ADHD受试者在特定程度上不会有区别 注意力技能受损，但他们的运动技能会不同 TS/ADHD和TS受试者都有更大的运动障碍 技能。具体目标2(注意力减退的药理学基础， 精细运动技能和冲动)解决了DA之间的关系 激活剂和特定认知和运动障碍的改变。 将解决的假设是：1)注意力受损是 通过激活D1受体而不是通过激活D2和/或D3而减少 2)精细运动技能受D2受体激活的影响， 但不是通过激活d1或d3受体；3)冲动性通过 激活D3受体，但不是通过激活D1和/或D2 感受器。 将对这些目标进行详细、全面的分析 多变量分析。目前还没有研究比较这种药物的效果。 不同多巴胺受体在不同类型细胞上的选择性激活 注意力受损的组成部分。也没有研究比较 药物治疗注意障碍儿童的疗效观察 病因学。