ADHD is the result of dysfunction in the expression of genes related to dopamine (DAT1) and norepinephrine (NET) transporters, as well as dopamine and serotonin receptors, among other genes. The initial imbalance may begin in a specific system, such as the dopaminergic system, but tends to spread and affect other neurotransmitters, creating a domino effect.
A dysfunctional dopamine-related gene can trigger a cascade of imbalances.
For example:
– A genetic variant that affects the production, reuptake or reception of dopamine can lead to an initial imbalance in the dopaminergic system.
– The brain, in its search for homeostasis (balance), will try to compensate for this initial dysfunction.
– This compensation may involve other neurotransmitters and hormones, such as norepinephrine, serotonin and glutamate, in addition to the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol, the stress hormone.
– However, this compensation is not always successful and can generate new imbalances in other neurochemical systems.
– The end result is a complex web of dysregulated interactions between multiple neurotransmitters and hormones, which manifests as the symptoms of ADHD.
Note: Although dopamine is often associated with ADHD, the initial dysfunction can occur in other neurotransmitter systems such as: norepinephrine, serotonin, glutamate, among others.
Example of Cascade of Imbalances
Imagine a genetic variant that impairs dopamine reuptake, leaving an excess of it in the synaptic cleft. The brain might try to compensate by reducing dopamine production or increasing the activity of receptors that inhibit it. However, this compensation could affect other systems, such as the norepinephrine system, which is closely linked to dopamine.
Relationship between dopamine and norepinephrine and other neurotransmitters:
1 – Dopamine is synthesized first from the amino acid tyrosine. Dopamine is then converted into norepinephrine by the enzyme dopamine beta-hydroxylase.
2 – Serotonin is synthesized from the amino acid tryptophan, in a pathway independent of dopamine and norepinephrine. However, these neurotransmitters interact in different regions of the brain, influencing each other. For example, serotonin can modulate the release of dopamine in certain areas, and dopamine can influence the activity of serotonergic neurons.
3 – Dopamine, norepinephrine and serotonin also interact with other neurotransmitters, such as glutamate and GABA, creating a complex communication network in the brain. Glutamate, for example, can stimulate the release of dopamine, while GABA can inhibit it.
ADHD is a complex and heterogeneous disorder, and the initial dysfunction may occur in several neurotransmitter systems, not just dopamine. The cascade of imbalances and subsequent compensations may vary depending on the system initially affected, but the end result is a complex interplay of dysregulations that manifest as the symptoms of ADHD.
Dr. Fabiano de Abreu Agrela Rodrigues MRSB holds a post-PhD in Neuroscience and is an elected member of Sigma Xi – The Scientific Research Honor Society (more than 200 members of Sigma Xi have received the Nobel Prize), as well as being a member of the Society for Neuroscience in the United States, the Royal Society of Biology and The Royal Society of Medicine in the United Kingdom, the European Society of Human Genetics in Vienna, Austria, and the APA – American Philosophical Association in the United States. He holds a Master’s degree in Psychology and a Bachelor’s degree in History and Biology. He is also a Technologist in Anthropology and Philosophy, with several national and international degrees in Neuroscience and Neuropsychology. Dr. Fabiano is a member of prestigious high IQ societies, including Mensa International, Intertel, ISPE High IQ Society, Triple Nine Society, ISI-Society, and HELLIQ Society High IQ. He is the author of more than 300 scientific studies and 30 books. He is currently a visiting professor at PUCRS in Brazil, UNIFRANZ in Bolivia and Santander in Mexico. He also serves as Director of CPAH – Centro de Pesquisa e Análises Heráclito and is the creator of the GIP project, which estimates IQ through the analysis of genetic intelligence. Dr. Fabiano is also a registered journalist, having his name included in the book of records for achieving four records, one of which is for being the greatest creator of characters in the history of the press.