Genetics and ADHD

 

Last month, I attended the annual meeting of the American Academy of Child and Adolescent Psychiatry. I chaired a session on new work using molecular genetics to understand ADHD. The field has recently made some interesting progress via very large collaborative studies. These studies bring together DNA and ADHD diagnoses from tens of thousands of individuals from around the world. Using that powerful method, new genes associated with ADHD have recently been identified. However, the effects of these individual genes are too small to be clinically useful. Instead, they provide possible clues to biological pathways.

Genetic Risk Scores

One benefit of these large studies is they allow us to discover the tiny association of thousands of genes with ADHD. When these tiny effects are all added up, we can actually estimate an individual’s “genetic load” for ADHD. Now, this is only a partial statement. That genetic risk score does not cover all the genetic load that an individual has. It only covers the association with a particular type of genetic variant called a common single nucleotide repeat. Other kinds of gene effects are also known to be involved. But this type of summary score is a crucial step. It allows us to begin to see how genetic risk might work in the brain and behavior in ADHD.

The investigators in our session presented a series of papers showing novel approaches to this. Using a total genetic risk score, we were able to discover that the genetic effect on ADHD operates mostly through alterations in working memory, not in other cognitive functions. In the brain’s all-important subcortical development, we found that this common genetic risk does not explain reduction in key subcortical brain regions in ADHD—although it does help explain overall reduction in brain volume in ADHD, suggesting some alterations in early brain growth in ADHD are associated with genetic risk while other developmental changes are possibly related to environmental risk or else with other kinds of genetic effects. In fact, one of my colleagues at the symposium reported preliminary data suggesting that alterations in brain development are also associated with rare genetic mutations. Stay tuned!

Mood Disorder, or ADHD?

We also looked at genetic risk for mood disorders, and the common problem of anger outbursts and irritable and defiant behavior in ADHD. We found that these problems with mood regulation were actually related to ADHD genetic risk, not mood genetic risk. This implies that these problems with emotional regulation really may be part of the core syndrome of ADHD, not a comorbidity. This may have implications in the future for how we define and diagnose ADHD.

For now, it’s helpful to remember that ADHD is a mix of genetic and environmental influences, and to recognize that if your child has problems with tantrums, anger, and emotion, this may be part of the ADHD syndrome. However, it’s important to have a professional evaluation to rule out a mood disorder, because those problems still appear to increase the risk of new disorder onset in the future.

The Science:

Nigg JT, Gustafsson HC, Karalunas SL, Ryabinin P, McWeeney SK, Faraone SV, Mooney MA, Fair DA, Wilmot B. J Am Acad Child Adolesc Psychiatry. (2018). Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for AttentionDeficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 57(3):175-182.

 

Dr. Nigg cannot advise on individual cases for ethical, legal, and logistical reasons.