Imaging of cannabinoid type 1 receptor availability in attention deficit/hyperactivity disorder: an [18F]MK 9470 positron emission tomography study

注意力缺陷/多动障碍中大麻素 1 型受体可用性的成像：[18F]MK 9470 正电子发射断层扫描研究

• 批准号: 520580926
• 负责人: Privatdozentin Dr. Isabelle Miederer
• 金额: --
• 依托单位: Klinik für Psychiatrie und Psychotherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/520580926?language=en
• 关键词: Imaging; cannabinoid; type; receptor; availability

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood and is characterised by symptoms of attention deficit, hyperactivity and impulsivity. Dysfunction in the dopaminergic system and other systems has been observed at the neurotransmitter level, but the mechanisms underlying ADHD are incompletely understood. Treatment options for ADHD include psychotherapy and/or pharmacotherapy, with the stimulants methylphenidate and amphetamine being the first-choice substances acting on dopaminergic and noradrenergic systems. Despite their positive effects, their effectiveness is questioned because they do not meet the broader clinical needs of ADHD patients, especially in the longer term. A new and promising approach is to study the endocannabinoid system. Because of its widespread distribution in the brain and interaction with other neurotransmitter systems, the endocannabinoid system is increasingly recognised as playing a key role in psychiatric disorders. Impulsivity, which we discuss in more detail in this study, is mediated by a fronto-striatal network, and according to the "dual pathway model of ADHD", a distinction is made between underlying deficits in inhibition-related executive functions and reward-related functions. With regard to the endocannabinoid system, a negative correlation was shown between cannabinoid type 1 receptor availability in the striatum and the expression of impulsivity. This means that against the background of the dopamine hypothesis, the dopaminergic involvement in the striatum and in impulsivity in ADHD, as well as the interaction between the dopamine and the endocannabinoid system, it is conceivable that the endocannabinoid system is involved in the aetiology and pathogenesis of ADHD. The novel aspect of the planned study is to investigate the role of the endocannabinoid system in the striatum of (untreated) study participants with ADHD, to the best of our knowledge for the first time, using the cannabinoid type 1 receptor ligand [18F]MK-9470 and positron emission tomography. Further aspects relate to the investigation of cannabinoid type 1 receptor availability in the whole striatum, in the dorsal and ventral parts of the striatum (cf. "dual pathway model of ADHD") and the concentration of endocannabinoids in the blood of untreated study participants with ADHD and methylphenidate-treated study participants with ADHD. The result of the planned study is an important starting point for the development of new pharmacological therapy approaches for ADHD, which are currently lacking. The results will help to improve evidence-based therapeutic strategies for the treatment of ADHD.

注意力缺陷多动障碍(ADHD)是一种神经发育障碍，通常持续到成年，以注意力缺陷、多动和冲动的症状为特征。已经在神经递质水平上观察到多巴胺能系统和其他系统的功能障碍，但ADHD的发病机制尚不完全清楚。ADHD的治疗选择包括心理治疗和/或药物治疗，兴奋剂哌甲酯和苯丙胺是作用于多巴胺和去甲肾上腺素系统的首选物质。尽管它们有积极的效果，但它们的有效性受到质疑，因为它们不能满足ADHD患者更广泛的临床需求，特别是从长远来看。研究内源性大麻素系统是一种很有前途的新方法。由于其在大脑中的广泛分布以及与其他神经递质系统的相互作用，内源性大麻素系统越来越被认为在精神障碍中发挥着关键作用。在这项研究中，我们更详细地讨论了冲动性，它是由额纹状体网络调节的，并且根据“ADHD的双通路模型”，区分了与抑制相关的执行功能和与奖励相关的功能的潜在缺陷。关于内源性大麻素系统，纹状体中大麻素1型受体的可获得性与冲动的表达呈负相关。这意味着在多巴胺假说的背景下，在ADHD纹状体和冲动的多巴胺能参与，以及多巴胺和内源性大麻系统之间的相互作用的背景下，可以想象内源性大麻系统参与了ADHD的病因和发病机制。这项计划中的研究的新方面是首次利用大麻素1型受体配体[18F]MK-9470和正电子发射断层扫描，调查(未经治疗的)ADHD研究参与者纹状体中内源性大麻素系统的作用。其他方面涉及研究大麻素1型受体在整个纹状体、纹状体背侧和腹侧部分的可用性(参看。“ADHD的双途径模型”)以及ADHD患者未经治疗的研究参与者和接受哌醋甲酯治疗的ADHD研究参与者血液中内源性大麻素的浓度。计划中的研究结果是开发ADHD新的药物治疗方法的重要起点，目前尚缺乏这些方法。这一结果将有助于改进ADHD的循证治疗策略。