Zamzow Rachel M, Ferguson Bradley J, Ragsdale Alexandra S, Lewis Morgan L, Beversdorf David Q
a Interdisciplinary Neuroscience Program , University of Missouri , Columbia , MO , USA.
b Department of Biological Sciences , University of Missouri , Columbia , MO , USA.
J Clin Exp Neuropsychol. 2017 Aug;39(6):596-606. doi: 10.1080/13803395.2016.1252724. Epub 2016 Nov 13.
Autism spectrum disorder (ASD) is characterized by impairments in social communication as well as restricted, repetitive behaviors. Evidence suggests that some individuals with ASD have cognitive impairments related to weak central coherence and hyperrestricted processing. Reducing noradrenergic activity may improve aspects of network processing and thus improve cognitive abilities, such as verbal problem solving, in individuals with ASD. The present pilot study explores the effects of acute administration of the beta-adrenergic antagonist propranolol on verbal problem solving in adults and adolescents with ASD. In a within-subject crossover-design, 20 participants with ASD received a single dose of propranolol or placebo on one of two sessions in a double-blinded, counterbalanced manner. Verbal problem solving was assessed via an anagram task. Baseline measurements of autonomic nervous system functioning were obtained, and anxiety was assessed at baseline and following drug administration. Participants solved the anagrams more quickly in the propranolol condition, as compared to the placebo condition, suggesting a potential cognitive benefit of this agent. Additionally, we observed a negative linear relationship between response to propranolol on the anagram task and two measures of baseline autonomic activity, as well as a positive linear relationship between drug response and baseline anxiety. These relationships propose potential markers for treatment response, as propranolol influences both autonomic functioning and anxiety. Further investigation is needed to expand on the present single-dose psychopharmacological challenge and explore the observed effects of propranolol in a serial-dose setting.
自闭症谱系障碍(ASD)的特征是社交沟通障碍以及局限的、重复的行为。有证据表明,一些患有ASD的个体存在与弱中央连贯性和过度受限加工相关的认知障碍。降低去甲肾上腺素能活性可能会改善网络加工的某些方面,从而提高患有ASD个体的认知能力,如言语问题解决能力。本试点研究探讨了急性给予β-肾上腺素能拮抗剂普萘洛尔对患有ASD的成人和青少年言语问题解决能力的影响。在一项受试者内交叉设计中,20名患有ASD的参与者在两个疗程中的一个疗程以双盲、平衡的方式接受了单剂量的普萘洛尔或安慰剂。通过字谜任务评估言语问题解决能力。获取了自主神经系统功能的基线测量值,并在基线和给药后评估了焦虑情况。与安慰剂组相比,参与者在普萘洛尔组中更快地解出了字谜,这表明该药物具有潜在的认知益处。此外,我们观察到在字谜任务中对普萘洛尔的反应与两项基线自主活动测量值之间存在负线性关系,以及药物反应与基线焦虑之间存在正线性关系。由于普萘洛尔会影响自主功能和焦虑,这些关系提示了治疗反应的潜在标志物。需要进一步研究以扩展目前的单剂量精神药理学挑战,并探索普萘洛尔在连续剂量设置下观察到的效果。