Samenvatting
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, I 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 behavior, which are also relevant for ADHD. We further found that statistical methods that are able to take 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 behavior are made up of many parts that influence each other, parts that should not be studied in isolation if we wish to truly understand how they work.
In this dissertation, I 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 behavior, which are also relevant for ADHD. We further found that statistical methods that are able to take 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 behavior are made up of many parts that influence each other, parts that should not be studied in isolation if we wish to truly understand how they work.
Originele taal-2 | English |
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Kwalificatie | Doctor of Philosophy |
Begeleider(s)/adviseur |
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Datum van toekenning | 23-jan.-2017 |
Plaats van publicatie | [Groningen] |
Gedrukte ISBN's | 978-94-6295-548-6 |
Status | Published - 2016 |