General Psychopathology in Children : Epidemiological Studies of Biological Mechanisms

Co-occurrence of mental disorders is widespread and studies have identified a general psychopathology factor reflecting vulnerability to experience a range of psychiatric problems. However, the biological mechanisms underlying the co-occurrence of child psychiatric symptoms, such as emotional, aggression and attention problems, remain unclear. The main question of this dissertation was: which biological factors are associated with child psychopathology in general and which biological factors are specific to certain psychopathology domains?
First, we investigated the genetics of general psychopathology by estimating the single nucleotide polymorphism (SNP) heritability of a general psychopathology factor and by performing a genome-wide association study of total psychiatric problems in school-aged children. We found that the general psychopathology factor appears to be partly heritable and identified specific loci associated with general psychopathology. On a neural level, we investigated white matter microstructure. We observed that more white matter integrity across the brain was associated with lower levels of general psychopathology. At the same time, more white matter integrity across the brain was associated with higher levels of specific externalizing levels, after controlling for general psychopathology. Furthermore, higher levels of general psychopathology in childhood were predictive of psychiatric problems in adulthood and worse school performance.
Additionally, we studied epigenetic mechanisms and attention-deficit hyperactivity disorder (ADHD). We observed that DNA methylation levels at birth were associated with ADHD symptoms in childhood. Interestingly, DNA methylation levels during school-age were less robustly associated with ADHD symptoms. We also found that parents who had their children at an older age had children with fewer behavioral problems compared to younger parents.
Finally, we studied cortisol, a stress hormone related to psychiatric symptoms. We observed a low SNP heritability of acute cortisol levels. As cortisol levels are very dynamic, genetics may only explain little if an acute measurement is used. A more stable, and therefore potentially more genetically determined, measure of cortisol are hair samples. However, we observed that hair cortisol levels are higher in darker hair independent of ethnicity. This hair pigmentation bias needs to be taken into account in studies of multi-ethnic populations.
In summary, this thesis suggests that the co-occurrence of psychiatric symptoms in children can partly be explained by genetic factors and is related to global white matter microstructure in the brain.