Molecular Brain Science Research Department, Tannenbaum Centre for Pharmacogenetics, Centre for Addiction and Mental Health, Neurogenetics Section, Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Eur Child Adolesc Psychiatry. 2024 Jun;33(6):1675-1685. doi: 10.1007/s00787-022-02030-6. Epub 2022 Jul 7.
The global prevalence of attention-deficit/hyperactivity disorder (ADHD) is estimated to be between 6% and 7% in children worldwide. The pathophysiology of this heterogeneous neurodevelopmental disorder remains unknown. Mitochondrial dysfunction has been proposed as a possible contributing factor to the etiology of ADHD. There is limited literature available to help our understanding of this hypothesis, and thus we conducted a systematic review of the number and quality of studies pertaining to mitochondrial genetic alterations in ADHD. A systematic search was conducted in the relevant databases Medline (PubMed) and Embase up to March 2021. Inclusion criteria included randomized control trials, cross-sectional studies, and case-control studies. This search resulted in a total of 507 articles that emerged from the search criteria. Of these results, 10 primary research articles were selected for in depth review based on the inclusion and exclusion criteria. These studies all reported on mitochondrial genetic variation in ADHD cases such as increased copy number, single-nucleotide polymorphisms, and haplogroup associations. This initial review of the experimental literature suggests mitochondrial genetic variation, in both the mitochondrial DNA and nuclear-encoded mitochondrial genes, may indeed contribute to ADHD pathophysiology. The studies reviewed here provide promising evidence for future research to further examine the mitochondrial genetics contributing to ADHD pathophysiology. We suggest that expansion of investigations into mitochondrial mechanisms may have potential to inform new treatment options for ADHD.
全球范围内，儿童注意缺陷多动障碍（ADHD）的患病率估计在 6%至 7%之间。这种异质性神经发育障碍的病理生理学仍然未知。线粒体功能障碍已被提出作为 ADHD 病因的一个可能因素。关于这一假设，可用的文献有限，因此我们对 ADHD 中线粒体遗传改变的研究数量和质量进行了系统评价。在 2021 年 3 月之前，在相关数据库 Medline（PubMed）和 Embase 中进行了系统搜索。纳入标准包括随机对照试验、横断面研究和病例对照研究。该搜索共产生了 507 篇符合搜索标准的文章。根据纳入和排除标准，从这些结果中选择了 10 篇主要的研究文章进行深入综述。这些研究都报告了 ADHD 病例中线粒体遗传变异，如增加的拷贝数、单核苷酸多态性和单倍型关联。这篇对实验文献的初步综述表明，线粒体 DNA 和核编码线粒体基因中的线粒体遗传变异可能确实有助于 ADHD 的病理生理学。这里综述的研究为进一步研究导致 ADHD 病理生理学的线粒体遗传学提供了有希望的证据。我们建议，扩大对线粒体机制的研究可能有助于为 ADHD 提供新的治疗选择。
