Theories of emotion regulation and social engagement indicate that resting and reactive respiratory sinus arrhythmia (RSA), which reflect vagal activity, in early childhood can inform the development of social and emotional behaviors later in life. Low RSA at baseline and during a stressful task have been associated with symptoms of ED and disorders characterized by social impairments. The current study examined the mediating role of ED at 24-months-old (mo) on the prospective association between early infant resting and reactive RSA at 5 mo on social functioning outcomes at 48 mo, and the mediating role of social functioning at 24 mo on infant RSA at 5 mo and ED at 48 mo in 237 healthy children. It was hypothesized that ED would mediate the relationship between infant RSA and later childhood social function. Results largely indicated no support of the hypotheses and that there is no mediating effect of childhood ED on early RSA on later childhood social behavior; however, there was a significant relationship between infant resting and reactive RSA and later ED. Limitations and future directions for improving the methodology are addressed. / M.S. / Early childhood heart rate has been thought to influence the development of later child emotional and social development. The Polyvagal Theory suggests that low variability in heart rate, as measured by respiratory sinus arrhythmia (RSA), is related to greater difficulties in emotional and social behavior. Finding an underlying biological reason for emotional and social development can be important for understanding childhood psychological disorders. This research study examined healthy children at three different time points during development: 5 months old (mo), 24 mo, 48 mo. RSA was measured at 5 mo, and frustration levels and social abilities at 24 and 48 mo. It was hypothesized that low RSA at 5 mo predicts low social abilities at 48 mo because of high frustration levels at 24 mo. To rule out an alternate hypothesis, this study also tested if low RSA at 5 mo predicts high frustration levels at 48 mo because of low social abilities at 24 mo. The results of this study did not support the predictions and there was no evidence of emotional abilities affecting how RSA predicts later social abilities. Possible explanations for the lack of findings and ideas for future research were discussed.

Parmi les facteurs intervienant dans la régulation et le maintien du fonctionnement d'organes, le système nerveux autonome et la microcirculation jouent un rôle prépondérant. Chez les patients critiques, comme les patients en sepsis, des altérations de la balance sympatho-vagale et de la perfusion tissulaire peuvent survenir et avoir des conséquences majeures en matière de morbidité et mortalité. La mise en oeuvre de méthodes de détection précoces de ces perturbations pourrait donc contribuer à améliorer la survie des patients à risque. En effet, le suivi des paramètres hémodynamiques, comme classiquement réalisé lors de réanimation, peut s'avérer insuffisant pour détecter des altérations de perfusion tissulaire : lors de sepsis, des altérations microcirculatoires peuvent persister en dépit de la normalisation des paramètres macrocirculatoires et sont associées à un mauvais pronostic. Eu égard à la présence de dysfunctions microcirculatoires et du système nerveux autonome chez les patients critiques, ce travail de recherche s'est proposé d'évaluer l’impact de modulateurs du système sympathique sur la balance sympatho-vagale et la microcirculation. Pour ce faire, nous avons travaillé avec des modèles animaux et des animaux admis en centre hospitalier universitaire vétérinaire. Le suivi du système nerveux autonome s'est basé sur un nouvel index de mesure du tonus parasympathique (Parasympathetic Tone Activity ou PTA). En parallèle, la microcirculation a été évaluée par vidéomicroscopie (SDF, Sidestream Dark Field imaging). L'index PTA a démontré une performance correcte pour prédire les réactions hémodynamiques chez les chiens anesthésiés. Il a aussi permis de détecter une altération de la balance sympathique chez les chevaux admis pour une chirurgie de colique ainsi qu’une altération de la microcirculation en dépit des manoeuvres de réanimation. Les études précliniques sur l’impact de la perfusion d’esmolol et de dexmédétomidine dans un modèle porcin septique ont montré que, malgré leurs effets hémodynamiques potentiels, ces agents n’ont pas eu d’effet négatif sur la microcirculation. Ainsi, les résultats de ce travail suggèrent un effet bénéfique des modulateurs du système nerveux sympathique sur la microcicultion mais nécessite d'être confirmé à plus grande échelle / Among the factors involved in the regulation and maintenance of the organs’ functioning, the autonomic nervous system and the microcirculation play a preponderant role. In critical patients, such as septic patients, alterations in the sympathovagal balance and tissue perfusion may occur and have major consequences of morbidity and mortality. The implementation of early detection methods for these disturbances could therefore contribute to improve the survival of patients at risk. Indeed, the monitoring of hemodynamic parameters, as conventionally performed during resuscitation, may be insufficient to detect tissue perfusion alterations: during sepsis, microcirculatory changes may persist despite the normalization of macrocirculatory parameters and are associated with a bad prognosis. With regard to the presence of microcirculatory dysfunctions and autonomic nervous system alterations in critical patients, this research project proposed to evaluate the impact of modulators of the sympathetic system on the sympatho-vagal balance and microcirculation. In order to achieve this, we worked on animal models and animals admitted to the faculty’s veterinary hospital center. Monitoring of the autonomic nervous system was based on a new Parasympathetic Tone Activity (PTA) index. In parallel, the microcirculation was evaluated by videomicroscopy (SDF, Sidestream Dark Field imaging). The PTA index demonstrated a good performance in predicting hemodynamic reactions in anesthetized dogs. It also detected disturbances of the sympathetic balance in horses admitted for colic surgery as well as an alteration of microcirculation despite resuscitation maneuvers. Preclinical studies on the impact of esmolol and dexmedetomidine infusion in a septic swine model showed that, despite their potential hemodynamic effects, these agents did not have a negative effect on the microcirculation. Thus, these findings suggest a beneficial effect of the modulators of the sympathetic nervous system on the microcicultion, however, these resutls should be confirmed on a larger scale

The aim of this thesis is to provide insights into how previous negative social experiences and/or societal norms concerning body size influence social information processing. The first two studies included in this thesis were conducted in Germany, a society with high level of prejudice towards individuals with obesity. The third study was conducted in American Samoa, a society with low prejudice towards individuals with obesity. Study one (chapter 5.1) investigated potential alterations in social information processing and behavior in individuals with obesity compared to lean individuals by measuring heart rate and reaction times. To identify potential reasons for alterations in the individual’s personal history, the influence of weight-related teasing on social information processing was analyzed. In the second study (chapter 5.2), I examined how individuals with and without obesity respond to social inclusion and social exclusion by measuring affect and heart rate. Of special interest were subjective factors of body dissatisfaction and teasing experiences as potential influencing factors. Following this approach, the second study became a “travelling experiment” and was repeated in a Polynesian group on American Samoa (chapter 5.3), a country with a high obesity rate, but less negative social outcomes for individuals with obesity. It aimed at studying the influence of cultural norms and values related to body size as well as varying weight-related stigmatization on psychophysiological processing in social situations.:1 Introduction 2 Theoretical Background 2.1 Social exclusion and behavior 2.1.1 Evolutionary origins of social exclusion and stigmatization 2.1.2 Adaptive behavioral responses to recurrent negative social feedback 2.2 Social exclusion and affect 2.2.1 General biological aspects of emotions 2.2.2 Cultural aspects of emotions 2.2.3 Affect after social exclusion 2.3 Social exclusion and parasympathetic cardio-regulation 2.3.1 Parasympathetic cardio-regulation in psychological research 2.3.2 Parasympathetic cardio-regulation during negative social feedback 2.3.3 Methodological issues 2.4 Obesity in Western societies 2.4.1 Prevalence and health consequences 2.4.2 Obesity and parasympathetic cardio-regulation 2.4.3 The stigma of obesity 2.4.4 Obesity and social information processing 2.5 Obesity and the Samoan Islands 2.5.1 Geography and population 2.5.2 Traditional diets, modernization, and obesity prevalence 2.5.3 Cultural differences in the perception of body sizes 2.5.4 Body size perception in the Samoan Islands 2.5.5 Affect in Samoa 3 Rationale of the Experimental Work 4 Methods 4.1 Autonomic control of the heart 4.2 Heart rate variability analyses 5 Experimental Work 5.1 Study 1 – Differential heart rate responses to social and monetary reinforcement in women with obesity 5.2 Study 2 – Parasympathetic cardio-regulation during social interactions in individuals with obesity – The influence of negative body image 5.3 Study 3 – Body size-related socio-cultural norms in Westerners and Polynesians and their association with heart rate variability and affect during social interaction 5.3.1 Introduction 5.3.2 Methods 5.3.3 Results 5.3.4 Discussion 6 General Discussion and Implications 7 Summary 7.1 English summary 7.2 German summary 8 References 9 Appendix 9.1 Supplemental material 9.1.1 Participants: recruitment, inclusion and exclusion criteria 9.1.2 Overview procedures in Germany and American Samoa 9.1.3 Study 1 9.1.4 Study 2 9.1.5 Study 3 9.2 Declaration of authenticity 9.3 Authors' contributions 9.3.1 Study 1 9.3.2 Study 2 9.3.3 Study 3

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No. of bitstreams: 2 Dissertação - Carolina Nobre Ribeiro Pontes - 2018.pdf: 2152959 bytes, checksum: 9a1997dd7deceede7ede68d4550b490c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Previous studies suggested that the Angiotensin-(1-7) [(Ang-(1-7)] is able to modulate the cardiac sympathetic control and beta-adrenergic sensitivity. However, whether or not Ang-(1- 7) modulates the cholinergic activity in the heart remains unknown. The aim of this study was to evaluate the influence of Ang-(1-7) upon cholinergic sensitivity of hearts from normotensive and hypertensive rats. Wistar and Spontaneously Hypertensive Rats (SHR) were anesthetized with urethane and underwent catheterization of femoral artery and left ventricle to record the arterial and intraventricular pressure, respectively. Following, a dose-response curve of acetylcholine (ACh, 10, 20, 40 and 80 ng/Kg, i.v. into femoral vein) was performed in the absence or presence of Ang-(1-7) (7 x 10-12 mol/min), Mas receptor antagonist A-779 (7 x 10-11 mol/min) or Ang-(1-7)+A-779. Isolated hearts were perfused according to the Langendorff technique. Increasing concentrations of ACh (10-7 to 10-5 mol/L) were added to the hearts in absence or presence of Ang-(1-7), (2 x 10-11 mol/L), A-779, (2 x 10-10 mol/L), Ang-(1-7)+A-779, MrgD receptor antagonist, D-PRO (2 x 10-10 mol/L) or D-PRO+Ang-(1-7). ACh-induced vasorelaxation was assessed in absence or presence of Ang-(1-7) (2 x 10-11 mol/L or 2 x 10-10 mol/L). Ang-(1-7) attenuated the effect of ACh in decreasing the intraventricular systolic, dP/dt max and dP/dt min in anesthetized Wistar and SHR. These effects were blocked by A-779. Ang-(1-7) did not change the amplitude of the hypotensive effect evoked by ACh in Wistar or SHRs. In isolated hearts, Ang-(1-7) also attenuated the reduction of the intraventricular systolic pressure, dP/dt max and dP/dt min evoked by ACh. A-779 blocked the Ang-(1-7) effects in hearts from Wistar. A-779 or D-PRO did not modify the effects of Ang-(1-7) in hearts from SHR, but in presence of D-PRO, Ang-(1-7) effects were equipotent. Ang-(1-7) attenuated the vasorelaxation induced by ACh in aorta from SHR by only in SHR group. These data suggest that Ang-(1-7) exerts differential modulation of cardiac cholinergic sensitivity during experimental primary hypertension, which is independent on blood pressure. / Estudos prévios sugerem que a Angiotensina-(1-7) [(Ang-(1-7)] é capaz de modular o controle simpático cardíaco e sensibilidade beta-adrenérgica. Entretanto, ainda não se sabe se a Ang-(1-7) consegue modular a atividade colinérgica no coração. O objetivo deste estudo foiavaliar a influência da Ang-(1-7) na sensibilidade colinérgica cardíaca de ratos normotensos e hipertensos. Wistar e Ratos Espontaneamente Hipertensos (SHR) foram anestesiados com uretano e submetidos à canulação de artéria femoral e ventrículo esquerdo cardíaco para registro de pressão arterial e intraventricular, respectivamente. Em seguida, foi realizada uma curva dose-resposta de acetilcolina (ACh, 10, 20, 40 e 80 ng/Kg, i.v.) por infusão pela veia femoral. A infusão ocorreu na presença e ausência de Ang-(1-7) (7 x 10-12 mol/min), do antagonista do receptor Mas, A-779 (7 x 10-11 mol/min) ou de Ang-(1-7)+A-779. Os corações isolados foram perfundidos de acordo com a técnica de Langendorff e concentrações crescentes de ACh (10-7 a 10-5 mol/L) foram adicionadas aos corações na presença ou ausência de Ang-(1-7), (2 x 10-11 mol/L), A-779, (2 x 10-10 mol/L), Ang-(1-7)+A-779, antagonista do receptor MrgD, D-PRO (2 x 10-10 mol/L) ou D-PRO+Ang-(1-7). O vasorrelaxamento induzido pela ACh foi mensurado na presença ou ausência da Ang-(1-7) (2 x 10-11 mol/L ou 2 x 10-10 mol/L). Em Wistar e SHR anestesiados, a Ang-(1-7) atenuou o efeito da ACh na queda da pressão intraventricular sistólica, dP/dt máx, e dP/dt mín. Estes efeitos foram bloqueados pelo A-779. A Ang-(1-7) não alterou a resposta hipotensora da ACh em Wistar ou SHR. Nos corações isolados, a Ang-(1-7) também atenuou a redução na pressão intraventricular sistólica, dP/dt máx e dP/dt mín evocados pela ACh. O A-779 bloqueou os efeitos da Ang-(1-7) em corações de Wistar. O A-779 ou D-PRO, per se, não modificaram os efeitos da Ang-(1-7) em corações de SHR, mas na presença do D-PRO, a Ang-(1-7) apresentou efeitos similares. O vasorrelaxamento da aorta induzido pela ACh foi atenuado pela Ang-(1-7) apenas nos SHR. Estes dados sugerem que a Ang-¬(1-¬7) modula o sistema colinérgico cardíaco de forma diferente no modelo de hipertensão primária experimental e de maneira independente de ajustes na pressão arterial.