ADHD And The Role Of Dopamine And Stimulants
Medicine

ADHD And The Role Of Dopamine And Stimulants

Medical science has long suspected a connection between dopamine and ADHD. The first official link between the two was published in the journal Neuropsychiatric Disease and Treatment back in 2008, and ever since the race has been on uncover exactly how this relationship works. Dozens, if not hundred of papers later, science is finally beginning to draw a much clearer picture on how this condition develops; and with a better understanding how it develops, the closer we get to the more the chances of developing effective treatments and/or medications to combat ADHD, increases.

What is ADHD?

ADHD is a developmental disorder that affects a person’s focus and concentration. It is the most common mental health disorder in children; with onset starting between the ages of 3-12, and in many cases lasts long into adulthood.

Referred to in full as Attention-Deficit Disorder, ADHA interferes with the development of a child’s behavior. This leads to symptoms that manifest as inattentiveness, impulsiveness, and hyperactiveness.

Although the symptoms may initially seem mild compared with other mental health conditions, anyone familiar with the condition will agree it can be extremely tiring, not just for the patient but also for those around them.

This mental health condition affects a shocking amount of children worldwide; with reports estimating 5%–10% of all school children globally have the condition. It is more common in males than females, but persists into later life either sex.

If left untreated ADHA itself is not fatal, although it can lower life expectancy, Russell Barkley, Ph.D. explained in a 2022 ADDtitude article. Fortunately this reduced estimated life expectancy (ELE) can be reversed or at least mitigated.

What Causes ADHD?

ADHD is a polygenic disorder, with no single gene at the center of its cause. In fact, around 20 genes have been found to play a part in the development of the condition yet each only accounts for 5%, or less, of the phenotypic variance of ADHD. 

Studies have linked an estimated 80% of ADHD symptoms to genetic factors, suggesting that the disorder is highly unlikely to be the result of a single gene. ADHD frequently manifests as a wide spectrum of varying symptoms.

Despite knowing how ADHD develops and what genes are responsible, the reason why it occurs is still unclear. Some studies suggest a possible familial link, but this is inconclusive.

Close to being proven, researchers theorize that genetic risk factors, environmental factors, and rare psychiatric conditions in which specific environmental factors can be implicated with relative confidence are likely a combined cause.

Assessing these risk factors via genetic studies and then outlining the effect of these risk factors while analyzing specific genetics may help to demystify the exact role of genes in ADHD, which could ultimately help us discover how the mechanism of interaction between genetic and environmental factors triggers this condition.

How Is ADHD Treated?

To treat ADHD in children, doctors employ a multidisciplinary approach that consists of medication, psychological counseling, education, skills training, and, in some cases, behavioral therapy.

Medications containing methylphenidate or amphetamine, have become extremely popular as a prescription treatment for children with ADHD, however, some experts voice worries that they have been done so in worryingly large numbers; a concern that has prompted further research into the safety VS efficacy of the medication.

The treatment is highly effective, so much so that its eradication would certainly not be beneficial; instead, scientists took a deeper dive into understanding how methylphenidate/amphetamine works to treat ADHD and why it shows such consistent results. These findings will allow doctors to administer correct dosages that are both safe and effective. 

With a greater understanding of the role dopamine plays and the relationship it bears with ADHA, more effective medications can be developed, and existing medications can be better tailored to meet the needs of patients who will truly benefit.

Aside from medication, holistic treatments can offer an attractive solution for parents wanting to refrain from administering medication to their children

ADHD and Dopamine Research

Association between the dopamine transporter gene (DAT1) and attention deficit hyperactivity disorder-related traits in healthy adult.
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Barkley warns that ADHD is the worst life expectancy risk factor those with the condition face on a daily basis, more so than smoking, diabetes, unhealthy diet, lack of sleep, etc. This is partly because the symptoms of ADHA can aggravate the symptoms of other conditions, which can further exacerbate any other health issues and worsen a wide range of other ailments.

The good news is that there are natural ways you can help to reduce these common, everyday risk factors. To achieve this you can concentrate on bettering your:

  • Weight
  • Nutrition
  • Exercise
  • Sleep
  • Smoking and/or Alcohol use

Taking this approach provides multiple benefits; similarly to how addressing these factors can improve quality of life, the very same actions also help to treat ADHD. There is however, just one rather major trade off, patients must continue the treatments long into adulthood, essentially indefinitely, unless un-yet released break through technology

Dopamine And Stimulants For ADHA

The link between dopamine ADHD suggests that when inadequate dopamine is present, motivation and focus decrease, which in turn affects learning and memory.

This reduces the reward people with ADHD typically experience when completing tasks; making executive function a challenge, and distraction much easier. Stimulants increase the levels of dopamine, which, of course, works to combat this sluggish inactivity.

By understanding how the condition develops, we can begin to uncover what triggers its onset. And by understanding how the complex relationship between stimulants and ADHA fits together, scientists can develop ever more effective treatments and remedies, with the goal of having fewer side effects and/or adverse reactions.

ADHD Role Of Dopamine And Stimulants

What Does The Research Say

The main objective of the paper referred to in this article, was to review the results of studies investigating dopamine-related genes in ADHD. Compiling data from researchers across the board, the team was able to piece together information from various sources to produce coherent answers to their hypothesis.

Comprehensive Meta data analysis of dopamine-related genes in ADHD was carried out. One major area of interest was the dopamine transporter gene (SLC6A3) since methylphenidate is thought to inhibit the gene’s function by preventing pre-synaptic reuptake of dopamine.

In addition to analyzing psychostimulant drugs effect on dopamine transporters,

a magnetic resonance imaging technique and single-photon emission computerized tomography was also utilized to find abnormalities in neuroanatomical areas with rich dopamine innervations in ADHD children. Other studies suggest ADHD may also play a pivotal role in the motor function control; this was also examined.

Overall, the research found a strong link between the dopamine transporter (SLC3A6), the dopamine receptor 4 (DRD4), and ADHD.

Dopamine transporters and ADHD

Analyzing a myriad of genetic studies, the research consistently highlighted a link between the dopamine transporter (SLC3A6) and the dopamine receptor 4 (DRD4); further corroborating the hypothesis that the two are closely linked when it comes to factors responsible for ADHD.

Scientists think that methylphenidate stops this dopamine transporter (SLC3A6) from doing its job by stopping the pre-synaptic reuptake of dopamine. This causes more dopamine to be released into the extracellular space and more dopaminergic neurotransmission.

Striatal Dopaminergic Synapse

Striatal Dopaminergic Synapse

P. Fusar-Poli, K. Rubia, G. Rossi, G. Sartori, U. Balottin Striatal dopamine transporter alterations in ADHD: Pathophysiology or adaptation to psychostimulants? A meta-analysis. The American Journal of Psychiatry, 169 (3) (2012), pp. 264-272

To prove this, researchers created a dopamine transporter knock-out mouse, called Slc6a3-KO, which displayed behavioral traits highly reminiscent of ADHD characteristics. 

Indeed, the Slc6a3-KO mice became notably relaxed when given amphetamine or methylphenidate; a notably different effect from the average user, and one the researchers successfully hypothesized. Dopamine was also found to remain 100 times longer in the Slc6a3-KO mice than in wild-type animals.

Researchers then localized the human (SLC6A3) gene to investigate the association between SLC6A3 and ADHD using either the TDT or the HHRR test. Results showed a link in 3 of 4 groups who applied HHRR analysis, but only 1 of 6 groups using the TDT technique showed any relationship. These slightly skewed results could be for several reasons; either way, more research is needed to confirm the findings fully.

The relationship between the SLC6A3 and DRD4 genes and the link to ADHD seems to be one of the most replicated functions in the field of psychiatric genetics. When performed in such a manner, doctors can devise an effective way to decrease and increase synaptic levels of dopamine, which results in the ability to control ADHD symptoms. 

The findings seriously suggest the critical role dopamine systems play in the pathogenesis of ADHD.

The consistency of the research surrounding SLC6A3 and DRD4 bodes well for the future of ADHD treatments, whether that leads to the development of new medications, or a better understanding so the medication can be administered more safely and effectively.

In Conclusion

Despite the encouraging new findings, discovering one single cause of ADHD is highly unlikely since the condition is known as a polygenic disorder and is almost certainly caused by one of a number of different sources.

The medical community has high hopes that this branch of research will pave the way for approved ADHD treatments. But due to the heterogeneity of each patient’s symptoms, it’s unlikely that a one-size-fits-all remedy will come of this.

Nevertheless advancements in gene therapy, including revolutionary new techniques such as CRISPR, promise to transform how we treat certain conditions, and could see application in the altering of these transporter and receptor genes.

Additional research must take into careful consideration the polygenic nature of the disease, and plan precise and accurate phenotyping of children with ADHD in order to produce clear and accurate results.

By conducting larger studies that analyze symptoms and neuropsychological profiles, comorbid conditions and therapeutic responses to psychostimulant drugs, scientists can gain a greater insight into the true genetic makeup of ADHD, and eventually develop effective treatment and/or medication to combat this debilitating condition.