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自闭症谱系障碍中部分μ-阿片受体激动剂丁丙诺啡:病例报告。

The partial µ-opioid agonist buprenorphine in autism spectrum disorder: a case report.

机构信息

Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institute, Norra Stationsgatan 69, 113 64, Stockholm, Sweden.

Department of Psychology, University of Oslo Norway, Oslo, Norway.

出版信息

J Med Case Rep. 2022 Apr 15;16(1):152. doi: 10.1186/s13256-022-03384-w.

Abstract

BACKGROUND

There are currently no approved medications for impaired social cognition and function, core symptoms of autism spectrum disorder. We describe marked improvement of these symptoms with long-term low-dose administration of the partial µ-opioid agonist buprenorphine. We discuss these observations in the context of a role for endogenous opioid systems in social attachment, and theories integrating those findings mechanistically with autism spectrum disorder.

CASE PRESENTATION

M, a 43-year-old Caucasian male, is medically healthy. Despite social difficulties since childhood, he completed high school with better-than-average grades, but failed university education. A psychiatric evaluation in his twenties diagnosed attention deficit hyperactivity disorder but also noted symptoms of coexisting autism spectrum disorder. M accidentally came across buprenorphine in his late twenties and experienced progressively improved social functioning on a low daily dosage (0.5-1.0 mg/day), an effect maintained for 15 years. He lived independently and maintained a part-time occupation. After abrupt discontinuation of treatment, his autistic symptoms returned, and function deteriorated. Following evaluation by our team, buprenorphine was resumed, with gradual return to prior level of functioning. An attempt to formally evaluate M both on and off medication was agreed with him and approved by the Swedish Ethics Authority, but medication had to be resumed when the patient worsened following discontinuation.

CONCLUSIONS

According to the µ-opioid receptor balance model, both excessive and deficient μ-receptor activity may negatively influence social behavior, and accordingly both opioid agonist and opioid antagonist treatment may be able to improve social functioning, depending on an individual's opioid tone before treatment. Our case report is consistent with these hypotheses, and given the extensive unmet medical needs in individuals with autism spectrum disorders, randomized controlled trial appears warranted.

摘要

背景

目前,针对自闭症谱系障碍的核心症状,即社交认知和功能受损,尚无获批的治疗药物。我们描述了长期低剂量使用部分μ-阿片受体激动剂丁丙诺啡可显著改善这些症状。我们在讨论中探讨了内源性阿片系统在社交依恋中的作用,以及将这些发现与自闭症谱系障碍进行机制整合的理论。

病例介绍

M,一名 43 岁的白人男性,身体健康。尽管他自幼存在社交困难,但仍以高于平均水平的成绩完成了高中学业,但未能完成大学教育。他在二十多岁时接受的一次精神科评估诊断出患有注意力缺陷多动障碍,但也注意到了同时存在自闭症谱系障碍的症状。M 在二十多岁时偶然发现了丁丙诺啡,随后在低日剂量(0.5-1.0mg/天)下逐渐改善了社交功能,这种效果持续了 15 年。他独立生活并维持着一份兼职工作。停药后,他的自闭症症状再次出现,功能恶化。在我们团队对他进行评估后,重新开始使用丁丙诺啡,他逐渐恢复到之前的功能水平。我们与他商定并获得瑞典伦理委员会批准,对他进行药物治疗和停药后的正式评估,但当患者停药后病情恶化时,不得不恢复用药。

结论

根据μ-阿片受体平衡模型,过度和不足的μ-受体活性都可能对社交行为产生负面影响,因此阿片受体激动剂和阿片受体拮抗剂治疗都可能改善社交功能,具体取决于个体在治疗前的阿片受体状态。我们的病例报告与这些假设一致,鉴于自闭症谱系障碍患者存在广泛的未满足的医疗需求,进行随机对照试验似乎是合理的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4791/9011926/8822163f165e/13256_2022_3384_Fig1_HTML.jpg

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