The objective of this thesis was to investigate the long-term consequences of early maltreatment. In Chapter 1, a general introduction to this study is given. The main aim of the research was threefold: (1) to provide information about the consequences of early maltreatment on mental health problems later in life (2) to determine the relationship between early maltreatment and adult cortisol levels and explore possible modifying effects of pregnancy and internalizing psychiatric disorders on this association (3) to investigate a possible gene-environment interaction which could explain the large differences in response to early maltreatment with respect to externalizing behavior. It is difficult to demonstrate the specific risk of adversities very early in life for psychopathology. Maltreated children often remain in a problematic environment throughout childhood and adolescence. We tackled this challenge by using a sample of international adoptees who were taken out of their problematic environments and raised in presumably better conditions. This group of initially 2,148 international adoptees was followed from childhood to adulthood. In Chapter 2, we investigated if early childhood maltreatment is related to self-reported psychiatric disorders in adulthood. Children seemed quite resilient to the experience of moderately severe early adversities. However, when the adversities were severe or encompassed different forms, individuals had an increased likelihood of a psychiatric disorder in adulthood. We found some evidence that psychopathology due to early adverse experiences can appear de novo in adolescence or adulthood. In Chapter 3, we studied if abuse, neglect and multiple placements prior to adoption are associated with trajectories of parent-reported psychiatric problems from childhood to adulthood. Interestingly, we found that the effects of early adversities were not transient and the strength did not decrease over time. The experience of early maltreatment influenced the level of psychiatric problems. Especially when maltreatment was severe, problems were marked. The HPA axis, which is commonly referred to as the stress-system, is highly plastic during early life and therefore extreme stressful experiences occurring in this period, such as early adversities, can lastingly alter its set point and activity. In Chapter 4, we investigated long-term consequences of early adversities on the stress-system and observed that early neglect, and possibly abuse, affected the HPA axis. We found that severe neglect was associated with low levels of cortisol and a flattened day curve, while moderately severe early adversities might result in high levels of cortisol and a more dynamic diurnal cortisol rhythm. This suggests that with higher severity of maltreatment, the activity of the HPA system reaches a threshold and hypo- instead of hypercortisolism develops. In Chapter 5, we studied internalizing disorders in the adoptees, since it is suggested that these disorders are related both to early adversities and cortisol secretion. In non-maltreated participants with an anxiety disorder, cortisol secretion tended to be higher in comparison to non-maltreated participants without an anxiety disorder. In contrast, severely maltreated participants who also suffered from an anxiety disorder showed a tendency to have a lower cortisol production relative to controls. The interaction effect of early maltreatment and anxiety disorders with the total cortisol production was significant. When an anxiety as well as a mood disorder was present, cortisol levels of severely maltreated adoptees were particularly low. Summary 116 In Chapter 6, we described the modifying effect of pregnancy on the relationship between early maltreatment and cortisol secretion. Severely maltreated women are more likely to show lower total cortisol secretion than non-maltreated women. In contrast, when pregnant, severely maltreated women showed an increased total production of cortisol in comparison to women who were not maltreated early in life. Our findings suggest that in pregnancy, the experience of severe early adversity causes a marked increase of maternal cortisol above the high levels of cortisol that are normal in pregnancy. Such an exposure to an excess of glucocorticoids can affect the fetal brain and the HPA axis permanently, leading to several developmental and health problems in offspring. By this mechanism, severe early maltreatment could even affect the next generation negatively. Genes play a contributory role in influencing individual variations in the liability of certain traits and disorders. In many instances, the genes seem to operate through interplay with the environment. Several studies have found individual differences at a functional polymorphism in the promoter of the Monoamine Oxidase A (MAO-A) gene to partly explain the increased vulnerability in maltreated children with respect to the development of externalizing behavior. In these studies, MAO-A modifies the influence of early maltreatment on aggressive and delinquent behavior, with low activity of MAO-A seen as a risk factor and high activity of MAO-A seen as a protective factor to externalizing behavior in case of maltreatment. In Chapter 7, we observed, in 239 internationally adopted boys, that high MAO-A activity was associated with more externalizing behavior in comparison to international adoptees with MAO-A deficiency. No modifying effect of MAO-A was found on the relationship between early maltreatment and externalizing problems. Possibly, the drastic change in environment and the severity of early adversities could explain this lack of interaction. In Chapter 8, the main findings and conclusions of this thesis are summarized and discussed. The present thesis shows that early childhood adversities are associated with psychiatric problems throughout life, especially when maltreatment was severe. Adult cortisol levels are affected by the experience of early adversities and internalizing psychiatric disorders and pregnancy modify this relationship. Certain variants increase the likelihood of externalizing problem behavior, but this effect did not depend on the experience of early maltreatment. Several limitations of the present study and implications of the results are discussed.

, , ,
Sophia Foundation of Medical Research, Rottterdam
Erasmus MC: University Medical Center Rotterdam
F.C. Verhulst (Frank)
hdl.handle.net/1765/12616
Erasmus MC: University Medical Center Rotterdam

van der Vegt, E. (2008, February 13). The Impact of Early Childhood Adversities: A Study of International Adoptees. Retrieved from http://hdl.handle.net/1765/12616