Systematic review of mitochondrial genetic variation in attention-deficit/hyperactivity disorder

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.