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Neural correlates of gene-environment interactions in ADHD

PhD ceremony:Mr D. (Dennis) van der Meer
When:January 23, 2017
Supervisors:prof. dr. P.J. (Pieter) Hoekstra, prof. J.K. Buitelaar
Co-supervisor:dr. C.A. (Catharina) Hartman
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

The way we respond to our environment partly depends on our genes. So-called gene-environment interactions (GxE) may explain why some children develop attention-deficit/hyperactivity disorder (ADHD) when exposed to a stressful environment, whereas others do not. Knowledge of GxE may therefore not only contribute to a better understanding of this disorder, but also help in the development of prevention or treatment strategies that are tailored to the individual.

In this dissertation, we describe how we investigated the relation between genes, stress and ADHD. We found that genes regulating the activity of the brain’s stress response pathway explain differences between people in their sensitivity to stress. People with specific variants of the serotonin transporter (5-HTT) and the glucocorticoid receptor (NR3C1) genes showed a stronger relation between long-term exposure to stress and symptoms of ADHD. They also had lower brain volume and activity in brain areas important for the ability to control behaviour, which are also relevant for ADHD. We further found that statistical methods taking into account interactions between many genes and stressful experiences simultaneously, are particularly well-suited to predict ADHD severity.

We conclude that the GxE approach is valuable for developing a more nuanced understanding of the influence of genetic and environmental risk factors on ADHD and the brain. Our pattern of results illustrates that the biological systems underlying behaviour are made up of many parts influencing each other, parts that should not be studied in isolation if we wish to truly understand how they work.