Of Cortisol and Children: Hypothalamic-pituitary-adrenal (HPA) axis activity and the development of pre-schoolers in the general population

Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity can be determined by studying patterns of the diurnal cortisol rhythm. Cortisol, the end-product of the HPA axis, is important for an adequate stress reaction, but also for the daily bodily functions in humans. In healthy adults cortisol shows a diurnal rhythm, characterized by high levels in the morning due to a steep rise in cortisol shortly after awakening, followed by a decline in cortisol levels toward the evening. Development of this diurnal rhythm occurs during the first years of life. Many (child) psychiatric disorders (such as depression and ADHD) show dysregulation of the diurnal cortisol rhythm. However, it is unclear whether this dysregulation precedes the disorder or is a consequence of it. Epidemiological studies of the HPA axis in early life are lacking. Most of these studies focused on cortisol reactivity but have not addressed the diurnal rhythm. The present thesis is an attempt to close this gap.

The studies in this thesis were embedded in The Generation R Study, a large prospective population-based cohort from foetal life onwards in the city of Rotterdam, the Netherlands. At the age of 14 months the diurnal cortisol rhythm was measured through saliva sampling. It was shown that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in young children. Children with a diurnal rhythm, possibly indicative of dysregluation of HPA axis activity, also showed an increase in change of internalizing problems at the age of 3, but not externalizing problems, as well as a shorter sleep duration repeatedly measured through the age of 3 years.