Die Dissertation besteht aus einem Einleitungsteil sowie drei empirischen Zeitschriftenartikeln. Die Einleitung liefert den theoretischen Hintergrund, integriert die drei Zeitschriftenartikel und geht auf anknüpfende Forschungsfragen ein. Der erste Artikel befasst sich mit unterschiedlichen indirekten Messverfahren zur Erfassung impliziter Selbstwertschätzung und untersucht deren Reliabilität sowie konvergente und diskriminante Validität. Der zweite Artikel untersucht, wie Diskrepanzen zwischen impliziter und expliziter Selbstwertschätzung mit defensiven Reaktionen auf soziales Feedback zusammenhängen. Der dritte Artikel untersucht schließlich Zusammenhänge zwischen Selbstwertdiskrepanzen und Indikatoren psychischer und physischer Gesundheit. / The dissertation consists of an introduction and three empirical journal articles. The introduction gives the theoretical background, integrates the three journal articles, and elaborates on future research questions. The first article investigates the reliability and convergent and discriminant validity of implicit self-esteem measures. The second article examines, how discrepancies between implicit and explicit self-esteem are connected to defensive reactions to social feedback. The third article investigates the relationship of self-esteem discrepancies to indicators of mental and physical health.

To study of cognitive fear networks and associations, indirect experimental paradigms like the Implicit Association Test (IAT, Greenwald et al., 1998) or the Extrinsic Affective Simon Task (EAST, De Houwer, 2003) may be helpful, as they promise to assess the structure of specific associations using a performance based approach without having to ask the participant for a verbal report. Three studies investigated the usefulness and characteristics of IAT and EAST. The aim of the first study was to measure fear associations towards spiders among spider phobic and non-phobic participants as well as in a group of spider enthusiasts. Results indicate that the IAT paradigm is sensitive to the strength of fear relevant associations and able to predict anxious behavior beyond the predictions of direct measures such as questionnaires. The second study focused on some of the mechanisms that underlie IAT effects. With a newly developed masked IAT, these experiments investigated the influences of individual stimuli and superordinate categories on IAT performance. Besides theoretical implications, the results also provide practical, relevant applications for the use of IAT experiments. A third study applied the EAST to investigate how different context conditions lead to differential activation of cognitive schemata in fear of spiders. One can conclude that the impact of automatic threat associations depends on the activated context, and that the EAST is suitable for the assessment of fear associations and their current activation level. This dissertation leads to the conclusion that the performance based methodology of the IAT and EAST is a useful and practical approach to reflect fear associations in phobia indirectly. At this point, the use of indirect measures is still at its beginning, and requires intensive methodological and theoretical efforts. These paradigms, however, may become useful for possible implications in psychopathology and other fields of psychology.

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[pt] Neuroticismo é um fator de personalidade que engloba quatro subfatores: depressão, vulnerabilidade, passividade e instabilidade emocional. Esta pesquisa teve como objetivos construir e buscar evidências de validade de medidas implícitas para aferir as facetas de neuroticismo. Para tanto, foram realizados dois estudos: (1) elaboração dos itens; (2) teste empírico das medidas. O primeiro estudo consistiu em um procedimento empírico para selecionar itens e buscar evidências de validade baseadas no conteúdo das medidas construídas. Participaram 408 pessoas, sendo que todas eram estudantes universitárias. Esse procedimento resultou em listas de palavras representativas do indivíduo e das facetas de neuroticismo. No segundo estudo, as palavras selecionadas previamente foram implementadas em testes de associação implícita para que fossem buscadas mais evidências de validade e obtidos indicadores de fidedignidade. Participaram 417 pessoas com diferentes níveis de escolaridade, sendo que 72,2 por cento tinham ensino superior incompleto e 61,4 por cento eram mulheres. Os resultados indicaram que as medidas de depressão, insegurança e passividade apresentaram evidências de validade satisfatórias, incluindo uma estrutura consonante com as definições dos construtos e relações esperadas com outras variáveis. Por exemplo, encontraram-se correlações positivas entre as medidas construídas e neuroticismo e correlações negativas com satisfação de vida. A medida de instabilidade emocional, por outro lado, se mostrou mais problemática no que diz respeito às evidências de validade. Ainda, os índices de consistência interna de todas as medidas se mostraram adequados e os coeficientes de correlação teste-reteste foram superiores aos valores que têm sido encontrados na literatura. Discute-se, entretanto, que mais evidências de validade são necessárias para que essas medidas possam ser usadas em contextos aplicados. / [en] Neuroticism is a personality factor that encompasses four subfactors: depression, vulnerability, passivity and emotional instability. This research aimed to build and search for evidence of validity of implicit measures to assess the facets of neuroticism. For this purpose, two studies were conducted: (1) elaboration of the items; (2) empirical test of the measures. The first study consisted of an empirical procedure to select items and search for evidence of validity based on the content of the built measures. Participants were 408 people, all of them were university students. This procedure resulted in lists of representative words of the individual and the facets of neuroticism. On the second study, the previously chosen words were implemented on implicit association tests, so that more evidence of validity was sought and reliability indicators were obtained. Participants were 417 people with different levels of educational background, 72.2 percent of them had incomplete higher educational background and 61.4 percent were women. The results indicated that the measures of depression, insecurity and passivity presented satisfactory evidence of validity, including a structure aligned with the definition of the constructs and expected relations to other variables. For instance, we found positive correlations between the built measures and neuroticism and negative correlations with satisfaction with life. The measure of emotional instability, however, proved to be more problematic regarding the evidence of validity. In addition, the internal consistency indexes for all measures were found to be adequate and the test-retest correlation coefficients were higher than the values found in previous studies. It is argued, however, that more evidence of validity is needed so that these measures can be used in applied contexts.

La dysplasie fibromusculaire artérielle (DFM) est un groupe de pathologies vasculaires non inflammatoires, et non athéromateuses de la paroi artérielle. Elle est caractérisée par la sténose, l'occlusion, l’anévrisme ou la dissection des artères de petit et moyen calibres, en particulier les artères rénales et le tronc supra-aortique. La DFM est un facteur de risque de l’hypertension et de l’accident vasculaire cérébral. Elle touche essentiellement les femmes (80% des cas) de moins de 50 ans. La prévalence en population générale est inconnue et les estimations varient de 0.4% pour les formes cliniques à 4% dans une cohorte de donneurs de reins. Une agrégation familiale a été démontrée et une composante génétique suggérée. L'objectif de mon travail de thèse était de caractériser les bases génétiques la DFM. Dans la première partie, nous avons analysé des variants génétiques rares générés par séquençage d'exomes chez 16 cas apparentés de DFM issus de 7 fratries. Aucun gène majeur n’était muté pour l’ensemble des fratries ou pour au moins 3 fratries sur 7. Cependant, nous avons pu mettre en évidence puis validé un enrichissement en variants rares à fort potentiel fonctionnel de quatre gènes candidats pour la DFM (MYLK, OBSCN, DYNC2H1, RNF213) en combinant l’approche de séquençage d’exomes et l’étude d’association gène entier de 62767 variants rares (MAF < 5%) générés par génotypage avec la puce Exome-chip chez 249 cas non apparentés de DFM et 689 témoins. Cependant, l’implication de ces gènes dans la DFM doit être confirmée dans d’autres familles, et par des études de validations fonctionnelles. Dans la seconde partie, nous avons étudié l'association avec la DFM de 25606 variants fréquents (MAF ≥ 5%) de l’Exome-chip. Les résultats majeurs obtenus ont été répliqués dans une première étude (402 cas de DFM et 2537 témoins) puis dans 3 autres études incluant 512 cas de DFM et 669 témoins. La méta-analyse de l’ensemble a permis d’associer à la DFM le polymorphisme rs9349379-A situé dans l’intron du gène PHACTR1 (OR=1,39 [1,39-1,54] ; P=7,36 ×10-10). Ce variant est aussi un facteur de risque pour la maladie coronaire, la migraine et la dissection de l’artère cervicale. Des études complémentaires conduites chez 2458 volontaires non malades ont permis de montrer que l’allèle à risque pour la DFM, rs9349379-A est associé avec une augmentation de l’épaisseur intima média (P=1,97×10-4) et du rapport de la paroi sur la lumière artérielle (P=0,002), deux paramètres décrits comme augmentés chez les cas de DFM dans des études antérieures. Ensuite, PHACTR1 a été détecté par immunohistochimie dans l’endothélium et les cellules musculaires lisses de carotides dysplasiques et non dysplasiques avec une expression augmentée de PHACTR1 pour les porteurs de l’allèle à risque de DFM dans des cultures primaires de fibroblastes humains (N=86, P=0,003). Enfin, l’invalidation de Phactr1 chez le poisson zèbre conduit à une dilatation des vaisseaux indiquant un défaut du développement vasculaire. Ce travail confirme le caractère multifactoriel et hétérogène de la DFM et ouvre de nouvelles perspectives pour évaluer l’ensemble de la variabilité génomique des patients de DFM par des approches massives de génétique épidémiologique. / Fibromuscular dysplasia (FMD) is a group of nonatherosclerotic and noninflammatory vascular diseases leading to stenosis, aneurysm, dissection and/or occlusion of medium-sized arteries, in particular the renal and extracranial cervical arteries. Clinical manifestations of FMD are hypertension, dizziness, pulsatile tinnitus, transient ischemic attack or stroke, according to the involved arterial beds. FMD occurs predominantly (80% of cases) in females under 50 years with a variable prevalence estimation from 0.4% for asymptomatic clinical relevant forms to 4% in potential renal donors. The pathogenesis of FMD is unknown and a genetic origin is suspected given its demonstrated familial aggregation. The aim of my thesis work was to characterize genetic basis of FMD. In the first part of this thesis, we analyzed whole exome sequencing data in 16 related FMD cases from seven families. No gene harbors variants that were shared by all affected members in at least three out seven families. Using combined strategy of whole exome sequencing and gene based association study of 62,767 rare variants (MAF < 5%) generated by Exome‐chip arrays in 249 unrelated FMD cases and 689 controls, we have identified and validated an enrichment of rare and putatively functional variants in four candidates genes (MYLK, OBSCN, DYNC2H1 and RNF213). This results need to be validated in other FMD families and by functional analysis. In the second part, we analyzed 25,606 common variants (MAF ≥ 5%) generated by Exome‐chip array. Top loci were replicated in first replication study (402 cases and 2,537 controls) and in 3 others studies (512 cases and 669 controls). Meta-analysis of all including 1,154 unrelated FMD cases and 3,895 controls allowed identification of association between FMD and rs9349379-A (OR=1.39 [1.39-1.54]; P=7.4×10‐10). rs9349379 is intronic to PHACTR1, a risk locus for coronary artery disease, migraine, and cervical artery dissection. The analyses of geometrical parameters of carotids from 2,458 healthy volunteers indicated higher intima media thickness (P = 1.97×10‐4) and wall to lumen ratio (P = 0.002) in rs9349379‐A carriers, suggesting indices of carotid hypertrophy as previously described in carotids of FMD patients. Immunohistochemistry detected PHACTR1 in endothelium and smooth muscle cells of FMD and normal human carotids. The expression of PHACTR1 by genotypes in primary human fibroblasts showed higher expression in rs9349379‐A carriers (N=86, P=0.003). Phactr1 knockdown in zebrafish resulted in dilated vessels indicating subtle impairment of vascular development. This work confirms the multifactorial and heterogeneous genetic architecture of the FMD and opens new opportunities to evaluate all of genomic variability of FMD patients with massive genetic epidemiology approaches.

Die Dissertation besteht aus einem Einleitungsteil und drei empirischen Beiträgen. Die Einleitung gibt eine Einführung in das Themengebiet der Selbstwertschätzung und deren Erfassung mit indirekten Verfahren. Vor allem aber dient sie dazu, die empirischen Befunde der Beiträge zu integrieren. Die ersten beiden Artikel widmen sich der Überprüfung der psychometrischen Qualität indirekter Verfahren. Das Augenmerk des ersten Beitrags liegt auf der Prüfung, ob verschiedene indirekte Verfahren konvergieren und ob explizite und implizite Selbstwertschätzung korrespondieren, wenn implizite Selbstwertschätzung reliabel erfasst wird. Außerdem werden strukturelle Ähnlichkeiten der indirekten Verfahren in die Betrachtungen mit einbezogen. Der zweite Beitrag komplettiert die Untersuchungen zur Güte der Verfahren. Der Fokus dieses Beitrags liegt im Nachweis der prädiktiven Validität verschiedener indirekter Verfahren. Dabei werden Kriterien herangezogen, die nicht im Selbstbericht erhoben werden. Im Detail wird eine doppelte Dissoziation zwischen expliziter und impliziter Selbstwertschätzung geprüft. Der dritte Beitrag rundet diese Arbeit ab, da er sich auch einem anwendungsbezogenen Aspekt der Persönlichkeitspsychologie widmet. Untersucht wird der Zusammenhang zwischen defensiven Verhaltensweisen und Selbstwertdiskrepanzen, also der Kombination expliziter und impliziter Selbstwertschätzung. / The dissertation consists of an introduction and three empirical journal articles. The introduction gives the theoretical background about self-esteem and its assessment with indirect measures, and primarily, integrates the three journal articles. The first article investigates the reliability and convergent and discriminant validity of indirect measures of self-esteem. The second article complements the examination of the psychometric properties. It contributes evidence to the predictive validity of indirect self-esteem measures. With using non-self-reported criteria, a double dissociation between explicit and implicit self-esteem is tested. The third article brings into focus an applied aspect of personality psychology. It is analyzed how defensive reactions are related to self-esteem discrepancies, that are different combinations of explicit and implicit self-esteem.

Les maladies neurodégénératives, telles que la maladie d'Alzheimer (AD) et Charcot Marie Tooth (CMT), sont des maladies complexes. Leurs mécanismes pathologiques ne sont toujours pas bien compris et les progrès dans la recherche et le développement de nouvelles thérapies potentielles modifiant la maladie sont lents. Les données catégorielles, comme les échelles de notation et les données sur les études d'association génomique (GWAS), sont largement utilisées dans les maladies neurodégénératives dans le diagnostic, la prédiction et le suivi de la progression. Il est important de comprendre et d'interpréter ces données correctement si nous voulons améliorer la recherche sur les maladies neurodégénératives. Le but de cette thèse est d'utiliser la théorie psychométrique moderne: théorie de la réponse d’item pour analyser ces données catégoriques afin de mieux comprendre les maladies neurodégénératives et de faciliter la recherche de médicaments correspondante. Tout d'abord, nous avons appliqué l'analyse de Rasch afin d'évaluer la validité du score de neuropathie Charcot-Marie-Tooth (CMTNS), un critère important d'évaluation principal pour les essais cliniques de la maladie de CMT. Nous avons ensuite adapté le modèle Rasch à l'analyse des associations génétiques pour identifier les gènes associés à la maladie d'Alzheimer. Cette méthode résume les génotypes catégoriques de plusieurs marqueurs génétiques tels que les polymorphisme nucléotidique (SNPs) en un seul score génétique. Enfin, nous avons calculé l'information mutuelle basée sur la théorie de réponse d’item pour sélectionner les items sensibles dans ADAS-cog, une mesure de fonctionnement cognitif la plus utilisées dans les études de la maladie d'Alzheimer, afin de mieux évaluer le progrès de la maladie. / Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Charcot Marie Tooth (CMT), are complex diseases. Their pathological mechanisms are still not well understood, and the progress in the research and development of new potential disease-modifying therapies is slow. Categorical data like rating scales and Genome-Wide Association Studies (GWAS) data are widely utilized in the neurodegenerative diseases in the diagnosis, prediction and progression monitor. It is important to understand and interpret these data correctly if we want to improve the disease research. The purpose of this thesis is to use the modern psychometric Item Response Theory to analyze these categorical data for better understanding the neurodegenerative diseases and facilitating the corresponding drug research. First, we applied the Rasch analysis in order to assess the validity of the Charcot-Marie-Tooth Neuropathy Score (CMTNS), a main endpoint for the CMT disease clinical trials. We then adapted the Rasch model to the analysis of genetic associations and used to identify genes associated with Alzheimer’s disease by summarizing the categorical genotypes of several genetic markers such as Single Nucleotide Polymorphisms (SNPs) into one genetic score. Finally, to select sensitive items in the most used psychometrical tests for Alzheimer’s disease, we calculated the mutual information based on the item response model to evaluate the sensitivity of each item on the ADAS-cog scale.

Die Dissertation besteht aus einem Einleitungsteil und drei empirischen Beiträgen. Die Einleitung gibt eine Einführung in das Themengebiet der Selbstwertschätzung und deren Erfassung mit indirekten Verfahren. Vor allem aber dient sie dazu, die empirischen Befunde der Beiträge zu integrieren. Die ersten beiden Artikel widmen sich der Überprüfung der psychometrischen Qualität indirekter Verfahren. Das Augenmerk des ersten Beitrags liegt auf der Prüfung, ob verschiedene indirekte Verfahren konvergieren und ob explizite und implizite Selbstwertschätzung korrespondieren, wenn implizite Selbstwertschätzung reliabel erfasst wird. Außerdem werden strukturelle Ähnlichkeiten der indirekten Verfahren in die Betrachtungen mit einbezogen. Der zweite Beitrag komplettiert die Untersuchungen zur Güte der Verfahren. Der Fokus dieses Beitrags liegt im Nachweis der prädiktiven Validität verschiedener indirekter Verfahren. Dabei werden Kriterien herangezogen, die nicht im Selbstbericht erhoben werden. Im Detail wird eine doppelte Dissoziation zwischen expliziter und impliziter Selbstwertschätzung geprüft. Der dritte Beitrag rundet diese Arbeit ab, da er sich auch einem anwendungsbezogenen Aspekt der Persönlichkeitspsychologie widmet. Untersucht wird der Zusammenhang zwischen defensiven Verhaltensweisen und Selbstwertdiskrepanzen, also der Kombination expliziter und impliziter Selbstwertschätzung. / The dissertation consists of an introduction and three empirical journal articles. The introduction gives the theoretical background about self-esteem and its assessment with indirect measures, and primarily, integrates the three journal articles. The first article investigates the reliability and convergent and discriminant validity of indirect measures of self-esteem. The second article complements the examination of the psychometric properties. It contributes evidence to the predictive validity of indirect self-esteem measures. With using non-self-reported criteria, a double dissociation between explicit and implicit self-esteem is tested. The third article brings into focus an applied aspect of personality psychology. It is analyzed how defensive reactions are related to self-esteem discrepancies, that are different combinations of explicit and implicit self-esteem.

Indiana University-Purdue University Indianapolis (IUPUI) / Stigma is a barrier to recovery for people with mental illness. Problematically, stigma also has been documented among mental health practitioners. To date, however, most research has focused on explicit attitudes regarding mental illness. Little research has examined implicit attitudes, which has the potential to reveal evaluations residing outside of conscious control or awareness. Moreover, research has tended to use a mixed sample of practitioners and programs. The extent to which both explicit and implicit stigma is endorsed by mental health practitioners utilizing evidence-based practices is unknown. The purposes of the current study were to 1) carefully examine implicit and explicit stigmatizing attitudes, or biases, among Assertive Community Treatment (ACT) staff and 2) explore the extent to which explicit and implicit biases predicted the use of treatment control mechanisms. Participants were 154 ACT staff from nine states. They completed implicit (Implicit Association Test) and explicit measures of stigma. Overall, participants exhibited positive explicit and implicit attitudes towards people with mental illness. When modeled using latent factors, implicit, but not explicit bias significantly predicted the endorsement of restrictive or controlling clinical interventions. Practitioners who perceived individuals with mental illness as relatively more dangerous and helpless (both explicit and implicit), as well as participants from Indiana and those with less education were more likely to endorse use of control mechanisms. Thus, despite overall positive attitudes toward those with mental illness for the sample as a whole, even low levels of stigma at the individual level were found to affect clinical care. Mental health professionals, and specifically ACT clinicians, should work to be aware of ways in which their biases influence how they intervene with consumers.