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Risk of substance use among people with ADHD is also genetically determined

New Danish research shows that genetic markers for ADHD also increase liability to substance use. Girls are especially at risk.

People with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders. New Danish research recently published in Addiction shows that this risk is genetically determined to some extent.

The research results show that the higher the genetic risk score for ADHD a person with ADHD has, the higher the person’s risk of developing a substance use disorder. This association is stronger among girls than among boys.

“Other studies have shown a genetic correlation between ADHD and substance use, so this result may not be that surprising, but we are the first that have been able to show it with data,” explains Søren Dalsgaard, specialist physician in child and adolescent psychiatry and Professor, Department of Economics and Business Economics, Aarhus University.

Theresa Wimberley, postdoctoral fellow in the same department, conducted the study.

People with ADHD have a generally increased risk of substance use disorders

According to Søren Dalsgaard, people with ADHD have a well-known increased risk of developing substance use disorders.

In general, researchers estimate that people with ADHD have 3–5 times higher risk than people who do not have ADHD. However, specific knowledge is lacking on which factors can be used to predict whether people with ADHD develop substance use disorders.

The new study indicates that externalizing behaviour, parents’ possible mental disorders, low educational level and low parental income increase the risk of substance use.

In addition, the study indicates that the genetic risk factors for developing ADHD are also risk factors for developing substance use disorders among people with ADHD.

Examined genetic data from 13,116 Danes with ADHD

Theresa Wimberley and Søren Dalsgaard searched for risk markers for substance use among people with ADHD in data from various Danish registries, including the Danish Psychiatric Central Research Registry, the Danish National Patient Registry and other registries from Statistics Denmark.

The researchers also linked the data from these registries with data from the iPSYCH database, which contained the genetic data from 13,116 people with ADHD at the time of the study.

In this way, the research team investigated whether various factors and genetic risk markers for ADHD increase the risk of developing substance use disorders.

“In Denmark, we have the opportunity to link nationwide health registries, which is not possible in many other parts of the world. This gives us a unique opportunity to explore these associations,” explains Søren Dalsgaard.

Girls have a greater risk of developing substance use disorders than boys

Søren Dalsgaard has carried out other studies on gender differences among people with ADHD, and the results of the new study align very well with the previous studies. The previous studies have also shown that girls are especially vulnerable.

Søren Dalsgaard says that many people think that girls do not develop ADHD and that the girls who do seem to have ADHD anyway have some kind of “ADHD light” with lower severity than among boys.

But the healthcare system often detects only the most severe cases of ADHD among girls, and the research group recently showed that girls are diagnosed much later than boys – in fact, first as teenagers, although by definition ADHD begins before 7 years of age.

“This means that some girls may not be diagnosed for a long time and therefore may not get the help they need to avoid developing substance use disorders,” says Søren Dalsgaard.

Genetics only plays a minor role in the risk of substance use

Søren Dalsgaard says that genetic risk factors do not have as great an effect as other risk factors for substance use.

For example, externalizing behaviour is a considerably stronger risk factor than genetic liability.

Another example is age at diagnosis. People who are diagnosed with ADHD after 13 years of age have approximately 3 times higher risk of developing substance use than the people who are detected early and diagnosed with ADHD before they reach 13 years.

“This is probably because these people are not helped early. Going into their teenage years, many have developed problems that can lead to substance use disorders,” explains Søren Dalsgaard.

“We know that many factors increase the risk of substance use among people with ADHD, and now that we can quantify them, we can identify which risk factors should be in focus in clinical work.”

Further research can improve understanding of ADHD and substance use

The new research results improve researchers’ understanding of how genetics influences the development of both ADHD and substance use.

According to Søren Dalsgaard, the next step is examining the individual genetic risk markers in depth to determine whether some are more strongly associated with the risk of developing substance use disorders than others.

“Identifying some specific genetic risk markers for substance use disorders among people with ADHD may improve our understanding of the biology behind the association between ADHD and substance use. In the long term, determining where in the brain the genes are expressed and what transmitter substances they regulate may also be clinically relevant to understanding and treating ADHD and substance use. This may contribute to improving the basic understanding of both ADHD and substance use,” says Søren Dalsgaard.

Genetic liability to ADHD and substance use disorders in individuals with ADHD” has been published in Addiction. In 2016, the Novo Nordisk Foundation awarded Søren Dalsgaard a grant for the project Polygenic Risk Scores and Early Social Adversities in Predicting the Developmental Course and Trajectory in Individuals with ADHD.

Søren Dalsgaard
MD, Professor, Senior Researcher
CIRRAU provides the necessary and fundamental data infrastructure to support and conduct a large variety of register-based research projects ranging from intervention studies of vulnerable children and adolescents, through population-based genetic studies of mental disorders to nationwide population-based studies of a large variety of exposures, outcomes and consequences of outcomes. This project database is one of the world’s most comprehensive datasets in its combination of nationwide individual level information on health, firms and companies, family factors, social and contextual information, and it is further enriched with genetic information for 80,000 Danes. CIRRAU provides a data solution that constitutes the foundation for register-based analyses carried out in scientific programs supported financially by the Lundbeck Foundation, TrygFonden, EU, The Stanley Medical Research Institute, The Simon Foundation and NordForsk. So far, CIRRAU has provided fundamental data-infrastructure for research projects attracting well above DKK 300 million and supported research projects leading to more than 130 papers in scientific peer-reviewed journals. Many of these papers were published in some of the most high-ranking scientific journals. These include Science, Nature, The Lancet, Epidemiology, Biological Psychiatry, Human Reproduction, JAMA Psychiatry, Journal of Applied Econometrics, Journal of Health Economics, and Social Science and Medicine.