Fetal alcohol spectrum disorders in Finnish children and adolescents : diagnosis, cognition, behavior, adaptation and brain metabolic alterations

Alcohol consumption during pregnancy can potentially affect the developing fetus in devastating ways, leading to a range of physical, neurological, and behavioral alterations most accurately termed Fetal Alcohol Spectrum Disorders (FASD). Despite the fact that it is a preventable disorder, prenatal alcohol exposure today constitutes a leading cause of intellectual disability in the Western world. In Western countries where prevalence studies have been performed the rates of FASD exceed, for example, autism spectrum disorders, Down’s syndrome and cerebral palsy. In addition to the direct effects of alcohol, children and adolescents with FASD are often exposed to a double burden in life, as their neurological sequelae are accompanied by adverse living surroundings exposing them to further environmental risk. However, children with FASD today remain remarkably underdiagnosed by the health care system. This thesis forms part of a larger multinational research project, The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (the CIFASD), initiated by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in the U.S.A. The general aim of the present thesis was to examine a cohort of children and adolescents growing up with fetal alcohol-related damage in Finland. The thesis consists of five studies with a broad focus on diagnosis, cognition, behavior, adaptation and brain metabolic alterations in children and adolescents with FASD. The participants consisted of four different groups: one group with histories of prenatal exposure to alcohol, the FASD group; one IQ matched contrast group mostly consisting of children with specific learning disorder (SLD); and two typically-developing control groups (CON1 and CON2). Participants were identified through medical records, random sampling from the Finnish national population registry and email alerts to students. Importantly, the participants in the present studies comprise a group of very carefully clinically characterized children with FASD as the studies were performed in close collaboration with leading experts in the field (Prof. Edward Riley and Prof. Sarah Mattson, Center for Behavioral Teratology, San Diego State University, U.S.A; Prof. Eugene Hoyme, Sanford School of Medicine, University of South Dakota, U.S.A.). In the present thesis, the revised Institute of Medicine diagnostic criteria for FASD were tested on a Finnish population and found to be a reliable tool for differentiating among the subgroups of FASD. A weighted dysmorphology scoring system proved to be a valuable additional adjunct in quantification of growth deficits and dysmorphic features in children with FASD (Study 1). The purpose of Study 2 was to clarify the relationship between alcohol-related dysmorphic features and general cognitive capacity. Results showed a significant correlation between dysmorphic features and cognitive capacity, suggesting that children with more severe growth deficiency and dysmorphic features have more cognitive limitations. This association was, however, only moderate, indicating that physical markers and cognitive capacity not always go hand in hand in individuals with FASD. Behavioral problems in the FASD group proved substantial compared to the typically developing control group. In Study 3 risk and protective factors associated with behavioral problems in the FASD group were explored further focusing on diagnostic and environmental factors. Two groups with elevated risks for behavioral problems emerged: length of time spent in residential care and a low dysmorphology score proved to be the most pervasive risk factor for behavioral problems. The results underscore the clinical importance of appropriate services and care for less visibly alcohol affected children and highlight the need to attend to children with FASD being raised in institutions. With their background of early biological and psychological impairment compounded with less opportunity for a close and continuous caregiver relationship, such children seem to run an especially great risk of adverse life outcomes. Study 4 focused on adaptive abilities such as communication, daily living skills and social skills, in other words skills that are important for gradually enabling an independent life, maintain social relationships and allow the individual to become integrated into society. The results showed that adaptive abilities of children and adolescents growing up with FASD were significantly compromised compared to both typically-developing peers and IQ-matched children with SLD. Clearly different adaptive profiles were revealed where the FASD group performed worse than the SLD group, who in turn performed worse than the CON1 group. Importantly, the SLD group outperformed the FASD group on adaptive behavior in spite of comparable cognitive levels. This is the first study to compare adaptive abilities in a group of children and adolescents with FASD relative to both a contrast group of IQ-matched children with SLD and to a group of typically-developing peers. Finally, in Study 5, through magnetic resonance spectroscopic imaging (MRS) evidence of longstanding neurochemical alterations were observed in adolescents and young adults with FASD related to alcohol exposure in utero 14-20 years earlier. Neurochemical alterations were seen in several brain areas: in frontal and parietal cortices, corpus callosum, thalamus and frontal white matter areas as well as in the cerebellar dentate nucleus. The findings are compatible with neuropsychological findings in FASD. Glial cells seemed to be more affected than neurons. In conclusion, more societal efforts and resources should be focused on recognizing and diagnosing FASD, and supporting subgroups with elevated risk of poor outcome. Without adequate intervention children and adolescents with FASD run a great risk of marginalization and social maladjustment, costly not only to society but also to the lives of the many young people with FASD.

Training executive functions in the laboratory and in real life : cognitive consequences of computer-based exercises and bilingualism

The question of the trainability of executive functions and the impact of such training on related cognitive skills has stirred considerable research interest. Despite a number of studies investigating this, the question has not yet been solved. The general aim of this thesis was to investigate two very different types of training of executive functions: laboratory-based computerized training (Studies I-III) and realworld training through bilingualism (Studies IV-V). Bilingualism as a kind of training of executive functions is based on the idea that managing two languages requires executive resources, and previous studies have suggested a bilingual advantage in executive functions. Three executive functions were studied in the present thesis: updating of working memory (WM) contents, inhibition of irrelevant information, and shifting between tasks and mental sets. Studies I-III investigated the effects of computer-based training of WM updating (Study I), inhibition (Study II), and set shifting (Study III) in healthy young adults. All studies showed increased performance on the trained task. More importantly, improvement on an untrained task tapping the trained executive function (near transfer) was seen in Study I and II. None of the three studies showed improvement on untrained tasks tapping some other cognitive function (far transfer) as a result of training. Study I also used PET to investigate the effects of WM updating training on a neurotransmitter closely linked to WM, namely dopamine. The PET results revealed increased striatal dopamine release during WM updating performance as a result of training. Study IV investigated the ability to inhibit task-irrelevant stimuli in bilinguals and monolinguals by using a dichotic listening task. The results showed that the bilinguals exceeded the monolinguals in inhibiting task-irrelevant information. Study V introduced a new, complementary research approach to study the bilingual executive advantage and its underlying mechanisms. To circumvent the methodological problems related to natural groups design, this approach focuses only on bilinguals and examines whether individual differences in bilingual behavior correlate with executive task performances. Using measures that tap the three above-entioned executive functions, the results suggested that more frequent language switching was associated with better set shifting skills, and earlier acquisition of the second language was related to better inhibition skills. In conclusion, the present behavioral results showed that computer-based training of executive functions can improve performance on the trained task and on closely related tasks, but does not yield a more general improvement of cognitive skills. Moreover, the functional neuroimaging results reveal that WM training modulates striatal dopaminergic function, speaking for training-induced neural plasticity in this important neurotransmitter system. With regard to bilingualism, the results provide further support to the idea that bilingualism can enhance executive functions. In addition, the new complementary research approach proposed here provides some clues as to which aspects of everyday bilingual behavior may be related to the advantage in executive functions in bilingual individuals.

Defending behavior in bullying situations

In order to encourage children and adolescents to defend and support their victimized peers, it is important to identify factors that either maximize or minimize the probability that students will engage in such behaviors. This thesis is composed of four studies designed to elucidate how a variety of factors work in conjunction to explain why some children defend their victimized classmates, whereas others remain passive or reinforce the bully. The conceptual framework of this thesis is drawn from several theoretical considerations, including social cognitive learning theory, the expectancy-value framework as well as the literature emphasizing the importance of empathy in motivating behaviors. Also the child-by-environment perspective and the socialecological perspective influenced this research. Accordingly, several intra- and interpersonal characteristics (e.g., social cognitions, empathy, and social status) as well as group-level factors (e.g., norms) that may either enhance or reduce the probability that students defend their victimized peers are investigated. In Studies I and II, the focus is on social cognitions, and special attention is paid to take into account the domain-specificity of cognition-behavior processes. Self-efficacy for defending is still an interest of study III, but the role of affective empathy on defending is also investigated. Also social status variables (preference and perceived popularity) are evaluated as possible moderators of links between intrapersonal factors and defending. In Study IV, the focus is expanded further by concentrating on characteristics of children’s proximal environments (i.e., classroom). Bullying norms and collective perceptions (i.e., connectedness among the students and the teachers’ ability to deal with bullying situations) are examined. Data are drawn from two research projects: the Kaarina Cohort Study (consisting of fourth and eighth graders) and the randomized controlled trial (RCT) evaluating the effects of the KiVa antibullying program (consisting of third to fifth graders). The results of the thesis suggest that defending the victims of bullying is influenced by a variety of individual level motivational characteristics, such as social cognitions and affective empathy. Also, both perceived popularity and social preference play a role in defending, and the findings support the conceptualization that behavior results from the interplay between the characteristics of an individual child and their social-relational environment. Classroom context further influences students’ defending behavior. Thus, antibullying efforts targeting peer bystanders should aim to influence intra- and interpersonal characteristics of children and adolescents as well as their social environment.

Understanding Online Game Players' Post-adoption Behavior: an Investigation of Social Network Games in China

Retaining players and re-attracting switching players has long been a central topic for SNG providers with regard to the post-adoption stage of playing an online game. However, there has not been much research which has explored players’ post-adoption behavior by incorporating the continuance intention and the switching intention. In addition, traditional IS continuance theories were mainly developed to investigate users’ continued use of utilitarian IS, and thus they may fall short when trying to explain the continued use of hedonic IS. Furthermore, compared to the richer literature on IS continuance, far too little attention has been paid to IS switching, leading to a dearth of knowledge on the subject, despite the increased incidence of the switching phenomenon in the IS field. By addressing the limitations of prior literature, this study seeks to examine the determinants of SNG players’ two different post-adoption behaviors, including the continuance intention and the switching intention. This study takes a positivist approach and uses survey research method to test five proposed research models based on Unified Theory of Acceptance and Use of Technology 2; Use and Gratification Theory; Push-Pull-Mooring model; Cognitive Dissonance Theory; and a self-developed model respectively with empirical data collected from the SNG players of one of the biggest SNG providers in China. A total of 3919 valid responses and 541 valid responses were used to examine the continuance intention and the switching intention, respectively. SEM is utilized as the data analysis method. The proposed research models are supported by the empirical data. The continuance intention is determined by enjoyment, fantasy, escapism, social interaction, social presence, social influence, achievement and habit. The switching intention is determined by enjoyment, satisfaction, subjective norms, descriptive norms, alternative attractiveness, the need for variety, change experience, and adaptation cost. This study contributes to IS theories in three important ways. Firstly, it shows IS switching should be included in IS post-adoption research together with IS continuance. Secondly, a modern IS is usually multi-functional and SNG players have multiple reasons for using a SNG, thus a player’s beliefs about the hedonic, social and utilitarian perceptions of their continued use of the SNG exert significant effects on the continuance intention. Thirdly, the determinants of the switch ing intention mainly exert push, pull, and mooring effects. Players’ beliefs about their current SNG and the available alternatives, as well as their individual characteristics are all significant determinants of the switching intention. SNG players combine these effects in order to formulate the switching intention. Finally, this study presents limitations and suggestions for future research.

Factors associated with adherence to antiretroviral therapy in HIV/AIDS patients: a cross-sectional study in Southern Brazil

A cross-sectional study was conducted on HIV-infected adults being treated with antiretroviral drugs at a reference service in Southern Brazil. Participants answered a sociodemographic questionnaire and were tested by scales assessing sociocognitive variables. Adherence to treatment was assessed by a self-report inventory developed for the study. Clinical information was obtained from the patients' records. Significance tests were conducted using univariate logistic regressions followed by multivariate logistic regression analysis. A total of 195 patients participated in the study and 56.9% of them reported > or = 95% adherence on the previous two days. In univariate analysis, the odds of adherence increased with self-efficacy (a person's conviction that he/she can successfully execute the behavior required to produce a certain desired outcome) in taking medications as prescribed (OR = 3.50, 95% CI 1.90-6.55), and decreased with perception of negative affect and physical concerns (OR = 0.71, 95% CI 0.53-0.95). The odds were lower for taking antiretroviral medications >4 times a day (OR = 0.44, 95% CI 0.20-0.94) and higher for patients with 8 years of schooling (OR = 2.28, 95% CI 1.12-4.66). In the multivariate analysis, self-efficacy (OR = 3.33, 95% CI 1.69-6.56) and taking medication >4 times a day (OR = 0.34, 95% CI 0.14-0.80) were independently associated with adherence. Self-efficacy was the most important predictor of adherence, followed by number of times antiretroviral medication was taken per day. Among sociodemographic and clinical variables, only the number of years of schooling was associated with adherence. Motivational interventions based on self-efficacy may be useful for increasing treatment adherence.

Gender-related pathways for behavior problems in the offspring of alcoholic fathers

The objective of the present study was to examine gender differences in the influence of paternal alcoholism on children's social-emotional development and to determine whether paternal alcoholism is associated with a greater number of externalizing symptoms in the male offspring. From the Mannheim Study of Risk Children, an ongoing longitudinal study of a high-risk population, the developmental data of 219 children [193 (95 boys and 98 girls) of non-alcoholic fathers, non-COAs, and 26 (14 boys, 12 girls) of alcoholic fathers, COAs] were analyzed from birth to the age of 11 years. Paternal alcoholism was defined according to the ICD-10 categories of alcohol dependence and harmful use. Socio-demographic data, cognitive development, number and severity of behavior problems, and gender-related differences in the rates of externalizing and internalizing symptoms were assessed using standardized instruments (IQ tests, Child Behavior Checklist questionnaire and diagnostic interviews). The general linear model analysis revealed a significant overall effect of paternal alcoholism on the number of child psychiatric problems (F = 21.872, d.f. = 1.217, P < 0.001). Beginning at age 2, significantly higher numbers of externalizing symptoms were observed among COAs. In female COAs, a pattern similar to that of the male COAs emerged, with the predominance of delinquent and aggressive behavior. Unlike male COAs, females showed an increase of internalizing symptoms up to age 11 years. Of these, somatic complaints revealed the strongest discriminating effect in 11-year-old females. Children of alcoholic fathers are at high risk for psychopathology. Gender-related differences seem to exist and may contribute to different phenotypes during development from early childhood to adolescence.

Adherence to drug therapy in kidney disease

Non-adherence to drug therapy has not been extensively studied in patients with chronic kidney disease (CKD). The objective of the present study was to identify determinants of non-adherence to drug therapy in patients with CKD, not on dialysis. A prospective cohort study involving 149 patients was conducted over a period of 12 months. Adherence to drug therapy was evaluated by the self-report method at baseline and at 12 months. Patients who knew the type of drug(s) and the respective number of prescribed pills in use at the visit preceding the interview were considered to be adherent. Patients with cognitive decline were assessed by interviewing their caregivers. Mean patient age was 51 ± 16.7 years. Male patients predominated (60.4%). Univariate analysis performed at baseline showed that non-adherence was associated with older age, more pills taken per day, worse renal function, presence of coronary artery disease, and reliance on caregivers for the administration of their medications. In multivariate analysis, the factors that were significantly associated with non-adherence were daily use of more than 5 pills and drug administration by a caregiver. Longitudinal evaluation showed an increase in non-adherence over time. Medication non-adherence was lower (17.4%) at the baseline period of the study than after 1 year of the study (26.8%). Compared to the baseline period, the percentage of adherent patients who became non-adherent (22%) was lower than the percentage of non-adherent patients who became adherent (50%). In CKD patients not on dialysis, non-adherence was significantly associated with the number of pills taken per day and drug administration by third parties. Adherence is more frequent than non-adherence over time.

Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience

INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

Psychological well-being of the parents and child development, behavior, and quality of life in very low birth weight infants

The parents of premature infants, especially the mothers, are at increased risk for distress. Infants born prematurely are at risk for developmental problems. The aim of this study was to investigate whether the psychological well-being of both parents is associated with child development in very low birth weight (VLBW, ≤1500g) children. The burden of prematurity-related morbidity to the children and to the family was also assessed. A cohort of 201 VLBW infants born during 2001–2006 in the Turku University Hospital, Finland, and their parents were studied (I–IV). One study included a control group (n=166) of full-term infants (IV). The psychological well-being of the parents was evaluated by assessments of depressive symptoms, parenting stress, the sense of coherence and general family functioning. Cognitive, behavioral, and socio-emotional development, and the health-related quality of life (HRQoL) of the children were determined when the children were 2 to 8 years old. The psychological well-being of the parents was associated with the cognitive, behavioral and social development of the VLBW children. The VLBW infants with prematurity-related morbidities had a poorer HRQoL and the general functioning of the family was inferior compared to the control children and their families. 64.5% of the VLBW children survived without morbidities. Most of the VLBW children did not have significant behavior problems (93%), had normal social skills (63%), had no emotional problems (64%), and had no problems in executive functioning (62%). Only 3% of the surviving VLBW infants had significant cognitive delay. In conclusion, the depressive symptoms and stress of the parents can be risk factors for disadvantageous child development, while a strong sense of coherence can be protective. Parents of the premature children with developmental delays might also experience more depressive symptoms and stress than other parents. Prematurity-related morbidities were a burden to the VLBW child as well as to the family.

The relation of attentional, emotional, and social regulation to cognitive competence, from infancy to school entry

Recent research on the sources of cognitive competence in infancy and early childhood has highlighted the role of social and emotional factors (for example, Lewis, 1993b). Exploring the roots of competence requires a longitudinal and multivariate approach. To deal with the resulting complexity, potentially integrative theoretical constructs are required. One logical candidate is self-regulation. Three key developmental questions were the focus of this investigation. 1) Does infant self-regulation (attentional, emotional, and social) predict preschool cognitive competence? 2) Does infant self-regulation predict preschool self-regulation? 3) Does preschool self-regulation predict concurrent preschool cognitive competence? One hundred preschoolers (46 females, 54 males; mean age = 5 years, 11 months) who had participated at 9- and/ or 12-months of age in an object permanence task were recruited to participate in this longitudinal investigation. Each subject completed four scales of the WPPSI-R and two social cognitive tasks. Parents completed questionnaires about their preschoolers' regulatory behaviours (Achenbach's Child Behavior Checklist [1991] and selected items from Eisenberg et ale [1993] and Derryberry & Rothbart [1988]). Separate behavioural coding systems were developed to capture regulatory capabilities in infancy (from the object permanence task) and preschool (from the WPPSIR Block Design). Overall, correlational and multiple regression results offered strong affirmative answers to the three key questions (R's = .30 to .38), using the behavioural observations of self-regulation. Behavioural regulation at preschool substantially predicted parental reports of regulation, but the latter variables did not predict preschool competence. Infant selfregulation and preschool regulation made statistically independent contributions to competence, even though regulation at Time 1 and Time 2 ii were substantially related. The results are interpreted as supporting a developmental pathway in which well-regulated infants more readily acquire both expertise and more sophisticated regulatory skills. Future research should address the origins of these skills earlier in infancy, and the social contexts that generate them and support them during the intervening years.

Évaluation d’une intervention infirmière basée sur une approche caring et cognitive comportementale sur l’acceptation d’un défibrillateur cardiaque implantable

Le taux de mortalité chez les patients à risque d’arythmies cardiaques menaçantes à la vie a été considérablement réduit grâce au défibrillateur cardiaque implantable (DCI). Toutefois, des préoccupations uniques face au DCI, y compris les chocs que l’appareil peut déclencher, sont susceptibles de provoquer des symptômes d'anxiété et une limitation perçue des activités chez les porteurs de DCI. Ces réactions émotives et modifications de comportement peuvent affecter l’acceptation du patient envers le DCI. Cette étude pilote randomisée avec groupe contrôle (n=15 /groupe) visait à examiner la faisabilité et l'acceptabilité d'une intervention infirmière individualisée de même que ses effets préliminaires sur l’anxiété, le fonctionnement dans les activités de la vie quotidienne et l’acceptation du DCI auprès de nouveaux porteurs de DCI. L'intervention infirmière, basée sur la théorie du Human Caring et teintée d’une approche cognitive comportementale, ciblait les préoccupations individuelles face au DCI. À partir des préoccupations identifiées, l’infirmière intervenait en mettant l'accent sur les croyances contraignantes du patient, qui pouvaient mener à de l’anxiété et des comportements d'évitement. Après randomisation, les patients du groupe intervention (GI) ont participé à un premier entretien en face-à-face avant le congé hospitalier. Subséquemment, deux entretiens se sont faits par téléphone, à environ 7 et 14 jours suite au congé hospitalier. Les résultats soutiennent la faisabilité et l’acceptabilité du devis de l’étude et de l’intervention évaluée. De plus, ils soulignent le potentiel de l’intervention à diminuer les sentiments anxieux chez les participants du GI. Les résultats de cette étude pilote offrent des pistes de recherches futures et permettront de guider la pratique clinique.

Warfarin-induced vitamin K deficiency is associated with cognitive and behavioral perturbations, and alterations in brain sphingolipids in rats

La Vitamine K (VK) est largement reconnue pour son rôle dans la coagulation sanguine toutefois, de plus en plus de travaux indiquent son implication dans la fonction cérébrale. La VK est requise pour l'activation de différentes protéines, par exemple la protéine Gas6, et la ménaquinone-4 (MK-4), le principal vitamère K dans le cerveau, est impliquée dans le métabolisme des sphingolipides. Dans un rapport précédent, nous avons montré qu'un régime alimentaire faible en VK tout au long de la vie était associé à des déficits cognitifs chez des rats âgés. La warfarine sodique est un puissant antagoniste de la VK qui agit en bloquant le cycle de la VK, provoquant un «déficit relatif de VK » au niveau cellulaire. À la lumière du rôle émergent de la VK dans le cerveau, la warfarine pourrait représenter un facteur de risque pour la fonction cérébrale. Ce travail est donc pertinente en raison de la forte proportion d'adultes traîtés à la warfarine sodique. Dans la présente étude, 14 rats mâles Wistar ont été traités avec 14 mg de warfarine/kg /jour (dans l'eau potable) et des injections sous-cutanées de VK (85 mg/kg), 3x/sem, pendant 10 semaines. Quatorze rats témoins ont été traités avec de l'eau normale et injectés avec une solution saline. Les rats ont été soumis à différents tests comportementaux après quoi les niveaux de phylloquinone, MK-4, sphingolipides (cérébroside, sulfatide, sphingomyéline, céramide et gangliosides), et les sous-types de gangliosides (GT1b, GD1a, GM1, GD1b), ont été évalués dans différentes régions du cerveau. Comparativement aux rats du groupe contrôle, les rats traités à la warfarine présentaient des latences plus longues au test de la piscine de Morris (p <0,05) ainsi qu'une hypoactivité et un comportement exploratoire plus faible au test de « l’open field » (p <0,05). Le traitement par warfarine a également entraîné une diminution spectaculaire du niveau de MK-4 dans toutes les régions du cerveau (p <0,001), une altération des concentrations de sphingolipidiques, en particulier dans le cortex frontal et le mésencéphale (p <0,05), et une perte de différences régionales sphingolipidiques, notamment pour les gangliosides. Le traitement par warfarine a été associé à un niveau inférieur de GD1a dans l'hippocampe et un niveau supérieur de GT1b dans le cortex préfrontal et le striatum. En conclusion, la déficience en VK induite par warfarine altère les niveaux de VK et sphingolipides dans le cerveau, avec de potentiels effets néfastes sur les fonctions cérébrales.

Institutions, Behavior and Evolution

The three articles constituting this thesis are for reasons of content or method related to the following three fields in economics: Behavioral Economics, Evolutionary Game Theory and Formal Institutional Economics. A core element of these fields is the concept of individual preferences. Preferences are of central importance for the conceptional framework to analyze human behavior. They form the foundation for the theory of rational choice which is defined by the determination of the choice set and the selection of the most preferred alternative according to some consistency requirements. The theory of rational choice is based on a very simplified description of the problem of choice (object function and constraints). However, that choices depend on many more factors is for instance propagated by psychological theories and is supported by many empirical and experimental studies. This thesis adds to a better understanding of individual behavior to the extent that the evolution of certain characteristics of preferences and their consequences on human behavior forms the overarching theme of the dissertation. The long-term effect of evolutionary forces on a particular characteristic of importance in the theoretical, empirical and experimental economic literature, the concept of inequality aversion, is subject of the article “The evolution of inequality aversion in a simplified game of life” (Chapter 4). The contribution of the article is the overcoming of a restriction of former approaches to analyze the evolution of preferences in very simple environments. By classifying human interaction into three central economic games, the article provides a first step towards a simplified and sufficiently complete description of the interaction environment. Within such an environment the article characterizes the evolutionary stable preference distribution. One result shows, that the interaction of the aforementioned three classes can stabilize a preference of inequality aversion in the subpopulation which is favored in the problem of redistribution. The two remaining articles are concerned with social norms, which dissemination is determined by medium-run forces of cultural evolution. The article “The impact of market innovations on the evolution of social norms: the sustainability case.“ (Chapter 2) studies the interrelation between product innovations which are relevant from a sustainability perspective and an according social norm in consumption. This relation is based on a conformity bias in consumption and the attempt to avoid cognitive dissonances resulting from non-compliant consumption. Among others, it is shown that a conformity bias on the consumption side can lead to multiple equilibria on the side of norm adoption. The article “Evolution of cooperation in social dilemmas: signaling internalized norms.” (Chapter 3) studies the emergence of cooperation in social dilemmas based on the signaling of social norms. The article provides a potential explanation of cooperative behavior, which does not rely on the assumption of structured populations or on the unmotivated ability of social norms to restrict individual actions or strategy spaces. A comprehensive result of the single articles is the explanation of the phenomenon of partial norm adaption or dissemination of preferences. The plurality of the applied approaches with respect to the proximity to the rational choice approach and regarding the underlying evolutionary mechanics is a particular strength of the thesis. It shows the equality of these approaches in their potential to explain the phenomenon of cooperation in environments that provide material incentives for defective behavior. This also points to the need of a unified framework considering the biological and cultural coevolution of preference patterns.

Embodied Autonomy in Digital Ecosystems: From Bio-Inspired Agents to Cognitive Systems

This paper proposes to promote autonomy in digital ecosystems so that it provides agents with information to improve the behavior of the digital ecosystem in terms of stability. This work proposes that, in digital ecosystems, autonomous agents can provide fundamental services and information. The final goal is to run the ecosystem, generate novel conditions and let agents exploit them. A set of evaluation measures must be defined as well. We want to provide an outline of some global indicators, such as heterogeneity and diversity, and establish relationships between agent behavior and these global indicators to fully understand interactions between agents, and to understand the dependence and autonomy relations that emerge between the interacting agents. Individual variations, interaction dependencies, and environmental factors are determinants of autonomy that would be considered. The paper concludes with a discussion of situations when autonomy is a milestone

Conducta suicida y consumo de alcohol y marihuana

En la actualidad tanto el consumo de alcohol y marihuana, como las conductas suicidas (ideación e intención suicida) en adultos jóvenes, constituyen un problema de salud pública cuyo impacto a nivel social y emocional, irrumpe el estilo de vida no sólo de quien es consumidor y lleva a cabo conductas suicidas sino al núcleo familiar y social circundante. Hay una especial preocupación por el temprano consumo de estas sustancias, oscilando entre los 15 años en el caso de los hombres y en las mujeres a los 18 años. El objetivo de esta revisión teórica es revisar la evidencia teórica y empírica sobre la conducta suicida (ideación e intención) y el consumo de alcohol y marihuana en adolescentes y adultos jóvenes. Entre otros, los resultados muestran que el consumo de alcohol y la conducta suicida están relacionados y que no hay evidencia empírica sobre la relación entre el consumo de marihuana y esta conducta.