Schizophrenia is a devastating mental disorder characterized by a hyperactive dopamine system and deregulated stress system. Human studies have suggested that the schizophrenia symptoms precipitate... Show moreSchizophrenia is a devastating mental disorder characterized by a hyperactive dopamine system and deregulated stress system. Human studies have suggested that the schizophrenia symptoms precipitate if a hyperactive dopaminergic genotype interacts with adverse life experiences that activate the stress system. To examine this gene-by-environment interaction, we exposed rats genetically-selected for enhanced apomorphine susceptibility to two stress-provoking life events, poor maternal care early-in-life, and isolation rearing later-in-life. This promoted the development of schizophrenia endophenotypes. Our experiments involved two complementary steps: First, we focused on the immediate endocrine adaptations to maternal separation in common rats. It is known that a single episode of prolonged maternal separation slowly increases corticosterone levels in the neonate rat. We discovered that if the pups had been previously exposed to maternal separation, this rise in corticosterone was abolished, suggesting that the pups had learned to predict the return of the dam. While readily adapting to repeated maternal absence, the pups, surprisingly, stayed alert and displayed a rapid response to an acute stressor. We then investigated whether pup__s stress responsiveness was influenced by the context of maternal separation. It appeared that the experience of being kept in isolation in a novel environment during repeated maternal separation, rather than the maternal absence per se, caused priming of the amygdala fear pathway, with lasting consequences for the responsiveness of the neuroendocrine and behavioral stress system. These endocrine and behavioral alterations, caused by early-life stress experience, consisted of schizophrenia-like phenotypes. Second, we sought to investigate the interplay of such early-life stress experience with schizophrenia genetic predisposition and/or later-life social stress experience. Thus, we were able to test the three-hit (cumulative stress) and the developmental mismatch hypotheses. The former states that exposure to earlylife adversity and later-life psychosocial stressors, superimposed on genetic susceptibility, result in a severe schizophrenia-like phenotype. The latter proposes that experiences early-in-life program the developing brain in preparation for the future. In the case of genetically-predisposed apomorphine susceptible rats (schizophrenia-susceptible), we provide strong evidence for the three-hit hypothesis. In the case of the nongenetically selected Wistar rats, the mismatch hypothesis is supported since the outcome of early-life stress often negatively interacted with the pre-puberty social context. In agreement with the three-hit hypothesis of schizophrenia, we conclude from the current experiments that early-life stress experience in interaction with highly reactive dopaminergic alleles, leads to amygdala priming that, together with additional stressors, precipitate schizophrenia. Show less
The book The United Nations, the Evolution of Global Values and International Law by Otto Spijkers describes how moral values have determined the founding of the United Nations Organization in 1945... Show moreThe book The United Nations, the Evolution of Global Values and International Law by Otto Spijkers describes how moral values have determined the founding of the United Nations Organization in 1945 and the evolution of its purposes, principles and policies since then. A detailed examination of the proceedings of the United Nations Conference on International Organization in San Francisco demonstrates that the drafting of the United Nations Charter was significantly influenced by global moral values, i.e. globally shared beliefs distinguishing right from wrong, good from bad, and the current from a preferable state-of-the-world. A common desire to eradicate war, poverty, inhuman treatment, and to halt the exploitation of peoples, has led to an affirmation of the values of peace and security, social progress and development, human dignity and the self-determination of all peoples. All these values ended up in the UN Charter. The book further analyzes how the United Nations, and especially its General Assembly, has continued to influence the maturing of global morality through contributions to the values-debate, and to the translation of these values into the language of international law, including the law on the use of force, sustainable development, human rights and the right to self-determination. Show less
This thesis shows the final results of a longitudinal project where the same participants (12 to 15 yrs.) were followed for three consecutive years. The first objective of this study was to... Show moreThis thesis shows the final results of a longitudinal project where the same participants (12 to 15 yrs.) were followed for three consecutive years. The first objective of this study was to investigate the development of both quantity and quality of metacognitive skills. The second objective was to establish whether the development of metacognitive skills is intelligence-related or relatively intelligence-independent. Finally, the generality vs. domain-specificity of developing metacognitive skills was investigated. While thinking aloud, participants performed two different tasks representing two different domains: A text-studying task and a problem-solving task. Participants__ intellectual ability was assessed, as well as their metacognitive skills and learning performance for both domains separately. In summary, this thesis has shown that (1) Metacognitive skills do increase spontaneously in frequency and quality during young adolescence, albeit not continuously. The various subscales of metacognitive skillfulness do not develop at the same pace; (2) Metacognitive skills have their own contribution to the prediction of learning performance, on top of intellectual ability. The relation between intellectual ability and metacognitive skills as predictors of learning performance is not affected by development between 12 and 15 yrs.; (3) Around the age of 15 yrs. metacognitive skills become fully general. Show less
It is well known that complex mental abilities develop at least until late adolescence. Yet, there are also skills that children master perfectly, sometimes even better than adults. The goal of... Show moreIt is well known that complex mental abilities develop at least until late adolescence. Yet, there are also skills that children master perfectly, sometimes even better than adults. The goal of this thesis was to learn more about the possibilities of cognitive functioning in children and young adults, and the constraints set by the developing brain. An fMRI training approach was used to examine age- and experience-related effects in the development of working memory and resting-state functional connectivity. More specifically, we studied age differences on task performance and brain activation during a working memory task with various demands and difficulty levels, both before and after 6 weeks of practice with the task. In addition, to learn more about the interaction between different brain regions, we also examined age differences and practice effects on functional connectivity during resting-state. Show less
