Chamberlain Samuel R, Müller Ulrich, Robbins Trevor W, Sahakian Barbara J
Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, UK.
Curr Opin Neurol. 2006 Dec;19(6):607-12. doi: 10.1097/01.wco.0000247613.28859.77.
Problems relating to impulsivity, attention, and working memory occur in many neuropsychiatric disorders and represent important targets for pharmacological intervention. The purpose of this article is to review recent neuropharmacological manipulation studies in humans relating to these domains.
Serotonin manipulations in healthy volunteers did not affect response inhibition, a cognitive function implicated in impulsive symptoms of attention deficit hyperactivity disorder, trichotillomania, and substance abuse. Serotonin manipulations did affect performance on cognitive tests involving emotionally salient rewards and feedback, suggesting involvement of this neurochemical in affective aspects of impulsivity. Attentional deficits in attention deficit hyperactivity disorder and visuospatial neglect were ameliorated by noradrenergic drugs. Noradrenergic beta-blockade suppressed the encoding of emotionally arousing unpleasant stimuli and reduced amygdala activation in healthy volunteers, with potential implications for posttraumatic stress disorder. Dopaminergic manipulations affected aspects of working memory in healthy volunteers and in patients with Parkinson's disease, with evidence for bidirectional effects depending on baseline performance.
Recent findings raise exciting prospects for modulating impulsivity, attention, and working memory in a variety of neuropsychiatric disorders. Future studies should use computerized cognitive assessment, measures of functional genetic polymorphisms, and neuroimaging techniques, in order to further elucidate the neurochemical substrates of cognition and optimize treatment approaches.
与冲动性、注意力及工作记忆相关的问题在多种神经精神疾病中均有出现，是药物干预的重要靶点。本文旨在综述近期针对这些领域开展的人体神经药理学操纵研究。
对健康志愿者进行血清素操纵并未影响反应抑制，反应抑制是一种与注意力缺陷多动障碍、拔毛癖及药物滥用的冲动症状相关的认知功能。血清素操纵确实影响了涉及情感显著奖励和反馈的认知测试表现，表明这种神经化学物质参与了冲动性的情感方面。去甲肾上腺素能药物改善了注意力缺陷多动障碍和视觉空间忽视中的注意力缺陷。去甲肾上腺素能β受体阻滞剂抑制了健康志愿者中情绪唤起不愉快刺激的编码并减少了杏仁核激活，这对创伤后应激障碍具有潜在意义。多巴胺能操纵影响了健康志愿者和帕金森病患者工作记忆的多个方面，有证据表明根据基线表现存在双向效应。
近期研究结果为调节多种神经精神疾病中的冲动性、注意力及工作记忆带来了令人兴奋的前景。未来研究应采用计算机化认知评估、功能性基因多态性测量及神经影像学技术，以进一步阐明认知的神经化学基础并优化治疗方法。
