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Unraveling the Neurochemical Knot: Dopamine and Serotonin in ADHD

Model of brain in cross-section and a model of a neuron


Attention-Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms such as inattention, hyperactivity, and impulsivity. The neurochemical underpinnings of ADHD have been the subject of extensive research, mainly focusing on the roles of dopamine and serotonin, two key neurotransmitters in the brain.

Dopamine's Role in ADHD:

Dopamine, a neurotransmitter associated with pleasure, reward, and motor function, is significantly implicated in ADHD. Research has consistently shown that individuals with ADHD may have lower levels of dopamine. This deficiency affects emotional regulation and the ability to seek and achieve specific rewards. The dopaminergic system, with its five distinct receptors (D1-D5), plays a critical role in the central nervous system, and its dysfunction has been linked to several neuropsychological diseases, including ADHD. Genetic studies have highlighted the importance of dopamine receptor genes (DRD5, DRD2, and DRD4) in the pathogenesis of ADHD, suggesting a high risk associated with polymorphisms in these genes​​​​.[1, 2]

Serotonin's Contribution:

Recent research has expanded the understanding of ADHD to include the role of serotonin, another critical neurotransmitter that regulates various brain functions, including mood and behavior. Serotonin's involvement in ADHD is evidenced through its regulation of dopaminergic neurotransmission in specific brain areas. Notably, the serotonin 5-HT1B receptor gene has been identified as a potential candidate for genetic studies in ADHD. The involvement of 5-HT1B receptors in locomotor behavior further supports the role of serotonin in ADHD. A study investigating the 5-HT1B G861C polymorphism found a significant paternal transmission of the G allele to children affected by ADHD, indicating serotonin genes as significant risk factors for the disorder​​​​.[3]

Interplay of Dopamine and Serotonin:

Recent genetic and neuroimaging studies further elucidate the complex relationship between dopamine and serotonin in ADHD. These studies suggest distinct contributions of altered dopamine and serotonin functions in ADHD, particularly in neurotransmitter uptake, synthesis, and breakdown. The interactions between dopamine and serotonin systems, especially at the level of receptors, are significant in understanding the neurochemical basis of ADHD. The findings suggest that the activity of serotonin might be anomalously higher or lower than the generally lower-than-normal levels of dopamine, potentially reflecting different diagnostic subgroups of ADHD and associated impulsive characteristics​​​​.[4]

Broader Genetic Perspective:

A comprehensive study involving 336 subjects examined 20 genes related to dopamine, serotonin, and noradrenergic metabolism in relation to ADHD. This study utilized multivariate linear regression analysis to assess the contribution of these genes to ADHD. It was found that adrenergic genes played a more significant role in ADHD compared to dopaminergic and serotonergic genes combined. Additionally, the study revealed that ADHD shares genetic components with other disorders like conduct disorder and oppositional defiant disorder (ODD), further supporting the need for simultaneous examination of multiple candidate genes in understanding ADHD​​.[5]


In conclusion, the interplay of dopamine and serotonin in ADHD underscores the complexity of this neurodevelopmental disorder. Understanding the nuanced roles of these neurotransmitters is vital in developing targeted therapeutic approaches and improving diagnostic accuracy. This research paves the way for a more integrated understanding of ADHD, considering both genetic predispositions and neurochemical imbalances.

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