This thesis describes the potential role of non-invasive measurement of pharmacokinetics (pk) and pharmacodynamics (pd) in the research and development of central nervous system (cns) stimulants or... Show moreThis thesis describes the potential role of non-invasive measurement of pharmacokinetics (pk) and pharmacodynamics (pd) in the research and development of central nervous system (cns) stimulants or depressants for children and adolescents. First, we evaluated the feasibility of using saliva as an alternative to plasma in two studies on psychostimulants (caffeine and methylphenidate). Second, neuropsychological and neurophysiological functions were measured longitudinally using the NeuroCart, a battery of tests developed at the Centre for Human Drug Research (chdr, Leiden, The Netherlands) that includes non-invasive tests for alertness, visuomotor coordination, motor control, memory, and subjective drug effects. Using a non-invasive approach, age-dependent differences in alcohol pk and pd were evaluated between healthy adolescents and adults. This thesis concludes with the report of two clinical trials that were designed to evaluate age-appropriate formulations of sedative drugs that have the potential for use in children. Show less
Depressie en angststoornissen, zoals major depressive disorder, paniekstoornis, sociale angststoornis en gegeneraliseerde angststoornis, vallen onder de meest voorkomende psychiatrische... Show moreDepressie en angststoornissen, zoals major depressive disorder, paniekstoornis, sociale angststoornis en gegeneraliseerde angststoornis, vallen onder de meest voorkomende psychiatrische ziektebeelden. Door middel van neuroimaging onderzoek zoals structurele en functionele MRI (fMRI) is het mogelijk om op een non-invasieve manier de onderliggende neurobiologie van deze stoornissen in kaart te brengen. Op basis van dergelijk onderzoek werden ruim 15 jaar geleden enkele neurobiologische modellen opgesteld waarin werd voorgesteld dat het goed of juist niet goed hersengebieden een belangrijke bijdrage leverde aan het ontstaan en/of instandhouden van depressie en angst. In de loop der jaren zijn nieuwe MRI technieken ontwikkeld. Met behulp van structurele MRI en resting-state fMRI, waarmee connectiviteit tussen hersengebieden onderzocht kan worden, heb ik gekeken naar anatomische en functionele hersenafwijkingen bij volwassenen en jongeren met depressie en/of angststoornissen. Doel was te bepalen of de reeds bestaande neurobiologische modellen bevestigd danwel aangepast of aangevuld zouden kunnen worden met recent ontwikkelde onderzoeksmethoden. De resultaten van mijn studies bevestigden grotendeels de betrokkenheid van de hersengebieden in de modellen, maar wezen tevens op een rol voor uitgebreidere netwerken van hersengebieden dan in de modellen werd verondersteld. Show less
The study aimed to investigate cross-cultural differences in the relation between community violence and psychopathology. A self-report survey was conducted in a representative sample of 3,309 14... Show moreThe study aimed to investigate cross-cultural differences in the relation between community violence and psychopathology. A self-report survey was conducted in a representative sample of 3,309 14-17 year old adolescents from urban communities in the US (N = 1,343), Belgium (N = 946) and Russia (N = 1,009). In all three countries, boys reported higher prevalences of violence exposure and more victimization by community violence than girls. Controlling for involvement in antisocial behavior, levels of psychopathology increased along with severity of exposure to community violence (from no exposure to witnessing to victimization). The associations between community violence and internalizing problems were similar across countries and gender. Current findings suggest that the relationships between community violence and adolescent mental health are not culture bound and that they follow similar dynamics in different populations. Clinical implications and directions are discussed. Show less
Improving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of... Show moreImproving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of malignant bone tumours of the lower extremity, there are a number of resection options (amputation, limb sparing, and rotationplasty) available. Each option has its own indication and after the surgery different advantages and disadvantages. The debate is whether limb-salvage or ablative surgery is advantageous for the individual patient. Purpose of the studies presented in this thesis are evaluate and compare QoL, functional ability and physical activity levels among children and young adults in the first years after bone cancer surgery of the leg. A cross sectional and a prospective study were conducted in the Dutch university bone cancer centres. The results of the cross-sectional study show that outcomes are equivalent for those undergoing limb salvage or ablative surgery. The results of the prospective study showed that; survivors improve in the two years following resection of the bone tumour and the resulting limb-sparing or ablative surgery at all domains evaluated, with the exception of the mental QoL domains. These improvements were most pronounced over the first year after surgery. Show less
Cross-cultural research shows that cultural frameworks provide guidance on what to feel and when, and how to express emotions from a young age. These cultural variations can cause misinterpretation... Show moreCross-cultural research shows that cultural frameworks provide guidance on what to feel and when, and how to express emotions from a young age. These cultural variations can cause misinterpretation and misunderstanding and are especially relevant for ethnic minority groups, who may be described as living ‘in between’ cultures. This thesis examines the extent to which Moroccan-Dutch adolescents’ emotional functioning can be considered in between cultures. Their emotion awareness, acknowledgment of social emotions, anger regulation, and anger communication was compared with those of their Dutch peers and with those of their peers living in Morocco. The thesis also addresses the adaptiveness of these aspects of emotional functioning in terms of psychological functioning. The results reveal that, overall, Moroccan-Dutch adolescents’ emotional functioning shows more similarities with that of their Dutch than their Moroccan peers. Although these ‘Dutch’ emotion patterns do not always seem adaptive for Moroccan-Dutch adolescents’ psychological wellbeing, the findings suggest that their emotional functioning in peer situations is a product of the Dutch culture. Show less
