Genetic testing and current pharmacological treatment options for ADHD

ADHD Genetic testing

To date, the cause of Attention Deficit Hyperactivity Disorder (ADHD) is still unknown. However, it is theorized that both genetic and environmental factors play a crucial role. To find out if indeed genetic factor is one of the determinants in the causation of the disease, a group of scientists from Cardiff University School of Medicine and deCode Genetics in Iceland, among other research centers, implemented a case-control study wherein children were enrolled as participants and they were divided in two groups. One group was composed of 366 children proven to have ADHD, otherwise known as the case subjects, and the other group was composed of 1,047 children without the disease, known as the control subjects—thus giving birth to the term case-control study [1].

The study specifically looked at whether large deletions and duplications within the DNA, otherwise known as the copy number variants or CNVs, are more common in the case subjects than in the control subjects. If the answer is yes, then it is highly possible that the variants play a role in causing the condition, and thus, in turn, linking genetic factors in the causation. If the link is established, then the remaining job is to definitely and conclusively identify the genes responsible for it [1]. Scientists believe that at least two genes are involved in the causation of ADHD [2].

The case-control study revealed that 14% of the case subjects had large and rare variations in their DNA while only 7% of the control subjects had them. These results provided evidence of an increased number of large CNVs in people with ADHD, refuting the hypothesis that it is highly and solely due to social factors [1].

Rare CNVs have been determined to contribute in the development of autism, intellectual disability, and schizophrenia. For this reason, researchers began to entertain the possibility that CNVs are also contributory to ADHD. They were very much interested in finding out if ADHD, autism, and schizophrenia could be linked to specific CNVs [1].

In a nutshell, the results of the current study reinforced what has been observed as the link of genetic risk factor to ADHD. However, these are neither meant to be used for care and treatment of ADHD patients nor to be used to develop any test for the disorder because there is no single gene behind ADHD and the present stage of the work is still too early to start developing any test [1].

While the preceding study admits that it is too early to develop a diagnostic test for ADHD, Dr. Alaitz Molano, a graduate in biochemistry and PhD holder in Pharmacology from the UPV/EHU-University of the Basque Country, launched a thesis work titled “Development of a genotyping system to be applied in Attention Deficit Hyperactivity Disorder and its Pharmacogenetics” which aims to open the door for prompt and accurate diagnosis of ADHD. The main thrusts of the study are to develop and clinically validate a genotyping tool that could help to confirm the diagnosis of ADHD, to predict how it will evolve, and to select the most suitable pharmacological treatment [3].

Dr. Molano has established the foundation of his proposal. He studied how genetic polymorphisms (variations in the DNA sequence between different individuals) are associated with ADHD. He and his colleagues analyzed about 400 saliva samples of patients with ADHD and another 400 samples from healthy controls. From these two sets of saliva samples, 250 polymorphisms were identified and selected. After further in-depth analysis, from the 250, 32 were selected as polymorphisms associated with ADHD. Based on this, Dr. Molano is proposing to produce DNA chips that will contain these polymorphisms as bases of not only confirming the diagnosing ADHD but to predict the possible evolution, the subtype, the severity, and the accompanying medical problems of the disorder [3].

Current pharmacological treatment options for ADHD

Stimulants

Amphetamine and methylphenidate

As the name implies, stimulants activate parts of the brain. In both animal and human studies, they were shown to “increase the alertness and energy, decrease tiredness, and improve ability to tend to even dull and repetitive tasks without errors”. It is believed that “these effects may be mediated by an increase in dopamine—a neurotransmitter involved in the reward centers of the brain” [4].

Although every drug has side effects, stimulants have several advantages. Firstly, these drugs have been studied more extensively than any other psychoactive drug prescribed for children. Secondly, they have repeatedly been shown to be safe and effective drug for reducing symptoms of ADHD, with 85 to 90 percent of children with combined-type ADHD responding well to one of the medications. Thirdly, they start and stop working quickly—that is, the effects of immediate release formulations begin within twenty to thirty minutes. After a few hours, they are eliminated from the body, and side effects are gone by the next day. Fourthly, for properly diagnosed patients, the benefits persist over time for the key symptoms of ADHD, and the patients do not become tolerant to the stimulant effects [4].

Some side-effects of the stimulants are appetite suppression, slower growth rate (height), insomnia, tics, irritability, and cognitive blunting.

Dextroamphetamine and levoamphetamine (Adderall)

Adderall is a combination of dextroamphetamine and levoamphetamine which are both stimulants, and they block the reuptake—and  increase the release—of norepinephrine and dopamine [5]. Based on the study by Faraon S.V. et al, Adderall prevented the worsening of patients and led to clinical improvements that were well into the normal range [6].

Use of Adderall may increase the blood pressure and heart rate,  and patients may experience heart palpitations. It is habit forming and chronic use may lead to dependence. Other known side effects of Adderall include nervousness, restlessness, excitability, dizziness, headache, fear, anxiety, tremor [7], insomnia, loss of appetite, nausea, and hallucination [8].

Non-stimulant medication

Atomoxetine (Strattera)

Atomoxetine is not a stimulant. While dopamine seems to be increased in the use of stimulants, atomoxetine increases norepinephrine, another form of neurotransmitter. In addition, it is safe and efficacious to use in children, adolescents, and adults with ADHD. Very striking about atomoxetine is that its beneficial effects could not be immediately observed, requiring  several weeks of daily use—even months—before they can be appreciated. Daily use is a must; “holidays” are neither feasible nor desirable [4].

The mechanism of action of atomoxetine has not been firmly established to date, but its big advantage is that it works more smoothly than stimulants, not only throughout the day and evening but also in the following morning. Thus, for children who need to be up and about in the morning, this medication is worth considering [4].

The main drawback of atomoxetine is that its sedative effect is very strong, causing daytime lethargy (profound slumber) in some patients. In addition, nausea and vomiting are observed. Like stimulants, atomoxetine’s benefits last over time, without necessarily increasing the dose except to accommodate changes in weight [4].

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