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
Human epidemiology and animal studies have convincingly shown the long-lasting impact of early life experiences on the development of individual differences in stress responsiveness in later life.... Show moreHuman epidemiology and animal studies have convincingly shown the long-lasting impact of early life experiences on the development of individual differences in stress responsiveness in later life. The interplay between genes and environment underlies this phenomenon.We provide an overview of studies investigating the impact of early life experiences on the development of individual differences in neuroendocrine stress responsiveness in adulthood and address (1) impact of environment on later stress phenotypes, (2) role of genetic factors in modulating the outcome of environment, and (3) role of nonshared environmental experience in the outcome of gene x environment interplays. We present original findings where we investigated the influence of nonshared experiences in terms of individual differences in maternal care received, on the development of stress phenotype in later life in rats.Environmental influences in early life exert powerful effects on later stress phenotypes, but they do not always lead to expression of diseases. Heterogeneity in response is explained by the role of particular genetic factors in modulating the influence of environment. Nonshared experiences are important in the outcome of gene x environment interplays in humans. We show that nonshared experiences acquired through within-litter variation in maternal care in rats predict the stress phenotype of the offspring.The outcome of early experience is not deterministic and depends on several environmental and genetic factors interacting in an intricate manner to support stress adaptation. The degree of "match" and "mismatch" between early and later life environments predicts resilience and vulnerability to stress-related diseases, respectively. Show less
Al jaren zijn we op zoek naar een hervorming van het kennisbeleid waar de ontwikkelingssector echt iets aan heeft. Hoogleraar Ton Dietz, directeur van het Afrika-Studiecentrum, schreef een manifest... Show moreAl jaren zijn we op zoek naar een hervorming van het kennisbeleid waar de ontwikkelingssector echt iets aan heeft. Hoogleraar Ton Dietz, directeur van het Afrika-Studiecentrum, schreef een manifest met vijf concrete verbeterpunten. Een noodkreet in historisch perspectief. Show less
