BIOCHEMICAL MECHANISMS UNDERLYING IMPAIRED ATTENTION

注意力受损的生物化学机制

• 批准号: 2259362
• 负责人: TIMOTHY P BOHAN
• 金额: $ 9.02万
• 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/2259362
• 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.

该提案解决了潜在的生化机制 儿童注意力受损。 主要目标是研究如何 注意力的组成部分和相关的神经行为过程受到影响 通过激活所有多巴胺 (DA) 受体（仅 D1）的药物 受体、D2 和 D3 受体，或仅 D3 受体。 我们建议 研究注意力的各个组成部分和相关的神经行为 对儿童和儿童进行系统的、多维度的评估 由于 (a) 注意力缺陷多动而注意力受损的成年人 障碍 (ADHD)，或 (b) 伴有或不伴有 ADHD 的抽动秽语综合症。 这些人群为解决以下问题提供了独特的机会： 儿童注意力受损是否具有相似的生化基础 无论其病因如何。 我们将调查几个方面的影响 不同的药物包括：a) 哌醋甲酯，b) 匹莫齐特，c) 溴隐亭和 d) 培高利特。 两个具体目标各有自己的设定 的假设将得到解决。 具体目标 1（受损的性质 注意）解决了病因之间的关系 注意力问题和注意力缺陷的模式。 我们将 评估注意力的不同组成部分，包括选择性和持续性 注意力、去抑制以及短期记忆和精细运动 技能。 目前尚不清楚这些因素如何随不同病因而变化 注意力障碍。 将要解决的假设是：1） ADHD 和 TS/ADHD 受试者在特定程度上没有差异 注意力技能受损，但运动技能有所不同 TS/ADHD 和 TS 受试者都有较大的运动障碍 技能。 具体目标 2（注意力受损的药理学基础， 精细运动技能和冲动）解决了 DA 之间的关系 特定认知和运动障碍的激活剂和改变。 将要解决的假设是：1）注意力受损 通过 D1 受体的激活而减少，但不通过 D2 和/或 D3 的激活而减少 受体； 2) 精细运动技能受到 D2 受体激活的影响， 但不是通过激活 D1 或 D3 受体； 3) 冲动性降低 D3 受体的激活，但不是通过 D1 和/或 D2 的激活 受体。 这些目标将得到详细、全面的分析 多变量分析。 目前尚无研究比较其效果 选择性激活不同的多巴胺受体 注意力受损的组成部分。 也没有研究比较 药物对因不同原因导致注意力受损的儿童的影响 病因学。