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Early ADHD Symptoms, Disease Course Have Different Genetic Roots

May 13, 2015

By Anne Harding

NEW YORK - The genetic factors that influence the course of attention-deficit/hyperactivity disorder (ADHD) are different from those involved in a patient's baseline level of symptoms, according to a new study of twins.

Little is known about environmental and genetic factors that influence the developmental course of ADHD, Dr. Jean-Baptiste Pingault, of University College London in the UK, and colleagues note in their report, online May 6 in JAMA Psychiatry.

While symptoms of hyperactivity/impulsivity tend to decline as a child gets older, they add, symptoms of inattention remain more stable or decline more slowly. Considerable inter-individual differences in symptom course occur, as well as differences in cerebral cortical development that have been linked to differences in outcome independent of baseline symptoms.

"Taken together, these findings suggest that, independent of the baseline level of ADHD symptoms, the heterogeneity between individuals in the developmental course of symptoms may be underpinned by differences in cortical trajectories and associated with differential prognosis," Dr. Pingault and colleagues say. "However, the origins of the inter-individual differences in ADHD symptoms (i.e., why they persist in some children and decline in others) are still largely unknown."

The researchers analyzed data on 8,395 twin pairs participating in the Twins Early Development Study. The data covered births in England and Wales between January 1994 and December 1996.

Each twin had ADHD symptoms assessed at least once between age 8 and 16. Hyperactivity-impulsivity scores decreased from 6.0 at age 8 to 2.9 at age 16. Additive genetic influences accounted for 90% of the baseline levels of these symptoms, while additive genetic influences explained 81% of the change in these symptoms over time.

Inattention symptoms also declined, from 5.8 at age 8 to 4.9 at age 16, but a "substantial minority" of the children showed an increase in these symptoms over time. Non-additive genetic factors accounted for 54% of the trajectory of inattention symptoms, and most of these influences were specific to the developmental course.

Taken along with previous research, "our findings suggest that the parallel developmental processes at the cortical and phenotypic levels might reflect specific genetic influences, mostly independent from those underlying the baseline status," Dr. Pingault and his team say.

They conclude: "For clinicians, the maintenance or increase in symptoms (a decline being normative in the population) might represent a marker of vulnerability reflecting genetic liability and warrant closer follow-up. It also raises the question of the necessity to inform patients and their relatives about the higher risk of persistence in families of index cases with persistent symptoms."

Dr. Stephen Faraone, a distinguished professor of psychiatry and of neuroscience and physiology at State University of New York Upstate Medical University in Syracuse, told Reuters Health in a telephone interview, "It's a very solid finding for sure. The idea that genes are involved in the whole persistence and remittance of symptoms makes a whole lot of sense."

Given the typical decline in symptoms of ADHD that begins in adolescence, doctors treating adolescents with the condition "should consider reducing their medication or eliminating it for a trial period to see if it's actually needed," Dr. Faraone said. And physicians should also remember, he said, that ADHD can look quite different in adults, who are more likely to have inattentiveness, distractability, and disorganization than hyperactivity.

Dr. Pingault did not respond to a request for comment by deadline.

The authors reported no funding or disclosures specific to this article.


JAMA Psychiatry 2015.

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