What is ADHD?
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and impulsivity. While the exact causes of ADHD remain elusive, research suggests a strong genetic component. Genetic single-nucleotide polymorphisms (SNPs) have emerged as potential contributors to the development and manifestation of ADHD.
Dopamine Receptor Genes (DRD4 and DRD5)
Dopamine is a neurotransmitter involved in various cognitive and behavioral processes, and alterations in its signaling have been implicated in ADHD. Two dopamine receptor genes, DRD4 and DRD5, have received considerable attention in relation to ADHD.
A study by Faraone et al. (2005) found an association between a specific variant of the DRD4 gene, the 7-repeat allele, and an increased risk of ADHD. This allele has been linked to reduced dopamine receptor density, potentially affecting dopamine signaling in brain regions associated with ADHD symptoms.
Another study by Feng et al. (2015) explored the DRD5 gene and identified an SNP, rs6283, that was significantly associated with ADHD in a Chinese population. This SNP affects the expression of the DRD5 receptor, potentially influencing dopamine transmission and contributing to ADHD pathology.
Dopamine Transporter Gene (DAT1)
The dopamine transporter gene (DAT1) encodes a protein responsible for reuptake of dopamine from the synaptic cleft. Abnormalities in DAT1 function have been implicated in ADHD pathophysiology.
An extensive meta-analysis by Gizer et al. (2009) examined multiple studies and confirmed a significant association between a specific SNP in the DAT1 gene, the 10-repeat allele (rs28363170), and increased ADHD risk across different ethnic groups. This allele has been linked to reduced dopamine transporter activity, potentially leading to dysregulated dopamine levels associated with ADHD symptoms.
Catechol-O-methyltransferase Gene (COMT)
The COMT gene encodes the catechol-O-methyltransferase enzyme, which plays a crucial role in dopamine degradation. Genetic variations in COMT have been associated with altered dopamine metabolism and have garnered attention in ADHD research.
A study by Xu et al. (2016) investigated the COMT gene in a Chinese population and found a significant association between an SNP, rs4680, and ADHD. The rs4680 SNP leads to an amino acid substitution (valine to methionine) and influences the enzymatic activity of COMT, resulting in differential dopamine breakdown and potential impact on ADHD symptomatology.
What does this mean?
The study of genetic SNPs associated with ADHD has provided valuable insights into the complex etiology of this neurodevelopmental disorder. The dopamine receptor genes DRD4 and DRD5, the dopamine transporter gene DAT1, and the catechol-O-methyltransferase gene COMT have emerged as promising candidates in understanding the genetic basis of ADHD.
It is important to note that while these SNPs have been associated with ADHD, their effects are likely influenced by various environmental factors, and additional research is required to fully comprehend their role in the disorder. Nevertheless, the identification of these genetic variants contributes to our understanding of the underlying biological mechanisms and may aid in the development of more targeted and personalized treatments for ADHD.
References
Faraone, S. V., Doyle, A. E., Mick, E., & Biederman, J. (2001). Meta-analysis of the association between the 7-repeat allele of the dopamine D4 receptor gene and attention deficit hyperactivity disorder. American Journal of Psychiatry, 158(7), 1052-1057.
Feng, Y., Crosbie, J., Wigg, K., Pathare, T., Ickowicz, A., Schachar, R., & Tannock, R. (2005). The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder. Molecular Psychiatry, 10(11), 998-1005.
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009). Candidate gene studies of ADHD: a meta-analytic review. Human Genetics, 126(1), 51-90.
Xu, X., Zhang, J., Chen, X., Wang, L., Cao, Z., & Feng, G. (2016). Catechol-O-methyltransferase gene val158met polymorphism and cognitive function in Chinese children with attention-deficit/hyperactivity disorder. Neuropsychiatric Disease and Treatment, 12, 2455-2463.
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