Attention-deficit/hyperactive disorder updates

Miriam Kessi; Haolin Duan; Juan Xiong; Baiyu Chen; Fang He; Lifen Yang; Yanli Ma; Olumuyiwa A Bamgbade; Jing Peng; Fei Yin

doi:10.3389/fnmol.2022.925049

Attention-deficit/hyperactive disorder updates

Front Mol Neurosci. 2022 Sep 21:15:925049. doi: 10.3389/fnmol.2022.925049. eCollection 2022.

Authors

Miriam Kessi^{1

2}, Haolin Duan^{1

2}, Juan Xiong^{1

2}, Baiyu Chen^{1

2}, Fang He^{1

2}, Lifen Yang^{1

2}, Yanli Ma³, Olumuyiwa A Bamgbade⁴, Jing Peng^{1

2}, Fei Yin^{1

2}

Affiliations

¹ Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
² Hunan Intellectual and Developmental Disabilities Research Center, Changsha, China.
³ Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
⁴ Department of Anesthesiology and Pharmacology, University of British Columbia, Vancouver, BC, Canada.

Abstract

Background: Attention-deficit/hyperactive disorder (ADHD) is a neurodevelopmental disorder that commonly occurs in children with a prevalence ranging from 3.4 to 7.2%. It profoundly affects academic achievement, well-being, and social interactions. As a result, this disorder is of high cost to both individuals and society. Despite the availability of knowledge regarding the mechanisms of ADHD, the pathogenesis is not clear, hence, the existence of many challenges especially in making correct early diagnosis and provision of accurate management.

Objectives: We aimed to review the pathogenic pathways of ADHD in children. The major focus was to provide an update on the reported etiologies in humans, animal models, modulators, therapies, mechanisms, epigenetic changes, and the interaction between genetic and environmental factors.

Methods: References for this review were identified through a systematic search in PubMed by using special keywords for all years until January 2022.

Results: Several genes have been reported to associate with ADHD: DRD1, DRD2, DRD4, DAT1, TPH2, HTR1A, HTR1B, SLC6A4, HTR2A, DBH, NET1, ADRA2A, ADRA2C, CHRNA4, CHRNA7, GAD1, GRM1, GRM5, GRM7, GRM8, TARBP1, ADGRL3, FGF1, MAOA, BDNF, SNAP25, STX1A, ATXN7, and SORCS2. Some of these genes have evidence both from human beings and animal models, while others have evidence in either humans or animal models only. Notably, most of these animal models are knockout and do not generate the genetic alteration of the patients. Besides, some of the gene polymorphisms reported differ according to the ethnic groups. The majority of the available animal models are related to the dopaminergic pathway. Epigenetic changes including SUMOylation, methylation, and acetylation have been reported in genes related to the dopaminergic pathway.

Conclusion: The dopaminergic pathway remains to be crucial in the pathogenesis of ADHD. It can be affected by environmental factors and other pathways. Nevertheless, it is still unclear how environmental factors relate to all neurotransmitter pathways; thus, more studies are needed. Although several genes have been related to ADHD, there are few animal model studies on the majority of the genes, and they do not generate the genetic alteration of the patients. More animal models and epigenetic studies are required.

Keywords: attention-deficit/hyperactive disorder; copy number variations; environmental factors; genes; microRNAs (miRNAs); pathogenic pathways.

Publication types

Review