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M.A. / none

M.Sc. / This thesis is a meeting of two disciplines: Chaos theory and psychopathology. Chaos theory developed out of mathematics, it aims to explain what is called a 'Chaotic system'. This is a system in which small changes lead to large effects: it is unstable, complex, and in continuous interaction with elements both within and outside of itself. According to this definition, human beings are inherently Chaotic systems. Psychopathology is the study of psychological disorder of human beings, including descriptions, etiologies and treatments. In the past, psychopathology was viewed as a 'modernist' science, seeking one-to-one relationships between cause, effect, symptom and treatment. With the rise of postmodernism, many theorists have criticised this view and sought out a more integrative, context-driven approach to understanding disorder. Although in its infancy, one of these approaches is the application of Chaos theory. In this thesis, the two disciplines meet around a theoretical analysis, and an exploration of a case study of Susan -a 'patient' diagnosed as having Bipolar Mood Disorder. Through exploring the life-story of Susan within the context of Chaos theory, we discover a new, integrative way of looking at 'disorder'1 its manifestations and our reactions to it. This thesis does not aim to give a definitive perspedive of Susan's life-story, or even of the two disciplines. Rather it aims to provide an academic framework for an application of Chaos theory to psychopathology. The thesis concludes that Chaos theory is a useful analogy in constructing a meaning and interpretation of psychopathology.

La obesidad y los trastornos de la conducta alimentaria (TCA) constituyen los mayores problemas que debe afrontar la salud pública en adolescentes, no solo por su alarmante prevalencia, sino también debido a sus serias consecuencias tanto físicas como psicosociales. Asimismo, se ha demostrado que la obesidad es un factor de riesgo para el desarrollo de los TCA, y que algunos de estos (principalmente aquellos de tipo bulímico) a su vez pueden favorecer el desarrollo y el mantenimiento de la obesidad. Todo esto sugiere un solapamiento en los factores de riesgo para la obesidad y los TCA. El hecho de comer o no comer, conlleva consecuencias, en el exceso como en la restricción, ocasionando enfermedades como la obesidad, el trastorno por atracón, la bulimia y la anorexia nerviosa. El presente trabajo está focalizado en el estudio de dichas patologías, las cuales son integradas bajo el rótulo de problemas relacionados con el peso y la alimentación. El objetivo central de esta tesis ha sido esclarecer la definición fenotípica-nosológica de los problemas relacionados con peso-alimentación. Para tal fin, se han llevado a cabo 4 estudios, mediante los que se analizaron semejanzas y diferencias entre pacientes con distintas patologías alimentarias (obesos con y sin TCA y TCA con y sin obesidad), en cuanto a psicopatología general, sintomatología alimentaria y personalidad (estudios 1 y 2); buscando además identificar factores de riesgo y factores asociados, específicos y compartidos (estudios 3 y 4) entre ambas patologías. Resultados: 1 La presencia de múltiples problemas relacionados con peso-alimentación (pe. TCA, Obesidad), a lo largo de la vida, es frecuente y va asociado a mayor gravedad psicopatológica y sintomatológica. 2 La obesidad sin TCA ocupa una posición intermedia en cuanto a psicopatología (general y alimentaria) entre controles en normo-peso, con menor psicopatología, y los TCA, en el extremo opuesto. 3 El perfil de personalidad de los obesos presenta similitudes con el perfil de los TCA, principalmente con BN y TA. Rasgos de personalidad disfuncionales como alta evitación del daño y baja autodirección están presentes en obesidad y en TCA pero con diferencias cuantitativas (apareciendo más acentuados cuanto mayor es la sintomatología alimentaria). 4 En cuanto a los aspectos socioculturales y familiares, algunas influencias alimentarias de la infancia, como un ambiente familiar negativo y las burlas de amigos sobre la figura corporal, fueron compartidas entre las situaciones extremas de peso (TCA en bajo peso y obesidad), mientras que otros factores fueron específicos de cada uno de ellos. 5 Determinados patrones alimentarios durante la infancia fueron especialmente relevantes en individuos obesos. 6 La asociación hallada entre BDNF y conciencia interoceptiva confirma la existencia de interacciones entre factores biológicos y psicopatológicos en conductas alimentaria anormales. Los resultados obtenidos van en concordancia con las evidencias empíricas que indican la existencia de nexos de unión entre los TCA y la obesidad. El solapamiento de distintos factores de riesgo y factores asociados entre ambas patologías aporta evidencia sobre la necesidad de tener en cuenta dichos nexos de unión en programas, tanto de prevención primaria como secundaria. / Introduction Obesity and eating disorders are, currently, the major problems among the teenager population that has to face social security. Not only due to its alarming prevalence, but also because of its serious physical and psychosocial consequences. Eating or not eating leads to consequences, both as excess or restriction, that cause diseases such as obesity, binge eating disorders (BED), bulimia nervosa (BN) and anorexia nervosa. The job presented here is focused in the study of such pathologies, which are integrated under the labeling of weight-related problems. Objectives: With the main objective of clarifying the phenotypic-nosological definition of weight-related problems, the thesis presented here aims at: 1- Analyze clinical variables (eating symptomatology and psychopathology) and traits of personality, common and specific, among people with different eating pathologies (Obese with or without ED and ED with or without obesity). 2- Identify risk and associated factors for weight-related problems. For this purpose, 4 independent but complementary research studies were developed: 1. Lifetime Obesity in Patients with Eating Disorders: Increasing Prevalence, Clinical and Personality Correlates. 2. Loss of Control Over Eating: a Description of the Eating Disorder/Obesity Spectrum 3. Eating Related Environmental Factors in Underweight Eating Disorders and Obesity: Are there Common Vulnerabilities during Childhood and Early Adolescence? 4. Correlation of BDNF Blood Levels with Interoceptive Awareness and Maturity Fears in Anorexia and Bulimia Nervosa Patients. Results: The results obtained are in agreement with the empirical evidences that point to the existence of commons links between ED and obesity. The presence of multiple lifetime weight-related problems is frequent and is associated with increased psychopathological and symptomatological severity. Obesity without ED occupies an intermediate position, in relation to psychopathology, among control group, with lower psychopathology, and the ED, in the opposite end. Dysfunctional personality traits such as high Harm Avoidance and low Self-Directedness are present in obesity and in ED but with quantitative differences (being worst when the eating symptomatology is more severe). Conclusion: The overlap of distinct risk and associated factors among both pathologies provides evidence for the need to take into account such links in prevention and treatment programs.

Thesis (Ph.D.) - University of Queensland, 2003. / Includes bibliography.

Cognitive impairment in the elderly encompasses many forms, ranging from subtle impairments in otherwise cognitively healthy individuals through mild cognitive impairment and dementia. Brain structural and functional changes underlie the observed cognitive impairment. Complementary to the clinical observation, biomarkers have been proposed as in vivo indicators of the underlying pathophysiology and neurobiological changes in a sufficiently reliable manner that they could be used to detect, track, and predict the disease course over time. In this thesis we used a combination of epidemiological and clinic-based approaches to investigate the mechanisms underlying vascular cognitive impairment (VCI) and Alzheimer’s disease (AD) and to identify possible biomarkers that could help early diagnosis of such conditions. To do so, a set of circulating and cerebrospinal fluid (CSF) biomarkers were studied in healthy and cognitively impaired subjects. Then, these measures were related to grey matter (GM) volumes, white matter (WM) integrity and cognition. The first two studies are part of the population-based Barcelona-ASIA neuropsychology study. Study I aimed to compare the cognitive patterns of risk markers for cerebrovascular disease (CVD) with the cognitive profile in relation to novel and traditional vascular risk factors (VRF) in a community-dwelling sample. Biomarkers of inflammation, endothelial dysfunction and vascular thrombosis were selected. Results showed that VRF and circulating markers of inflammation and endothelial dysfunction predicted performance in several cognitive domains. Cognitive patterns of inflammatory markers overlapped those related to VRF. Markers of endothelial dysfunction predicted lower performance in verbal memory. Study II was designed to further explore the structural changes mediating the relationships between risk markers of CVD and cognition. For that purpose the same set of markers of risk for CVD were related to GM atrophy and WM integrity and cognition. The main finding was an association of inflammation and vascular thrombosis with WM integrity loss in cortico-subcortical pathways and association fibres of frontal and temporal lobes. As expected, none of the biomarkers was related to GM volume changes. Vascular thrombosis also predicted lower performance in processing speed. The third study is a memory clinic-based investigation that was conducted aiming to test the potential use of CSF biomarkers cut-offs as components for the diagnostic work-up in AD. We assessed GM and cognitive patterns in cognitively impaired subjects using CSF Aβ1-42, t-tau and p-tau181 cut-offs as grouping criteria. Results indicated that patients with abnormal CSF levels of t-tau and p-tau (but not Aβ1-42) showed impairment and signs of regional GM atrophy in brain regions characteristic for AD, compared to those with normal levels. More specifically, GM volume differences were found in temporal, inferior parietal, lateral occipital and widespread prefrontal regions. Studies I and II show that risk markers of inflammation and vascular thrombosis are related to a VCI profile for both cognitive patterns and structural brain changes. A microvascular damage of WM projections in fronto-subcortical pathways, but not GM atrophy, could mediate the association between these pathogenic processes and cognitive performance. Markers of endothelial dysfunction are related to a different cognitive pattern which is characteristic of both vascular and neurodegenerative mechanisms. Study III provides evidence that patients with abnormal CSF levels of t-tau and p-tau (but not Aβ1-42) show cognitive an AD profile according to GM density patterns and cognitive impairment. Taken together, these results suggest that, complementary to the clinical observation, plasma and CSF markers and structural imaging are well placed to improve early diagnosis of both VCI and AD. / El terme deteriorament cognitiu (DC) es refereix al contínuum de canvis cognitius associats a l’envelliment sa i patològic. El diagnòstic precoç de les persones amb DC és clau, ja que els tractaments són més eficaços quan s’inicien als inicis de la malaltia. Els biomarcadors s’han proposat com a eines pel diagnòstic precoç del DC i la demència. Es consideren indicadors in vivo de la patologia i s’han plantejat com a possibles eines pel diagnòstic, pronòstic i seguiment del DC i la patologia subjacent. L’objectiu general de la present tesi era explorar els mecanismes patofisiològics subjacents al deteriorament cognitiu vascular (DCV) i la (MA). Per aquest motiu, vàrem mesurar diversos biomarcadors sanguinis i de LCR en persones sanes i en persones amb diagnòstic de deteriorament cognitiu i vàrem relacionar-los amb canvis de l’estructura cerebral i de la cognició. L’objectiu final era identificar possibles biomarcadors pel diagnòstic precoç d’aquestes malalties. Els estudis I i II s’emmarquen dins del projecte Barcelona-ASIA Neuropsicologia i tenien com a objectiu estudiar la relació entre biomarcadors en plasma de malaltia vascular cerebral (MVC) i canvis estructurals i cognitius. Els resultats obtinguts mostren que els biomarcadors d’inflamació i trombosi vascular es relacionen amb un perfil de deteriorament cognitiu vascular tant a nivell cognitiu com estructural. La lesió microvascular dels tractes de SB còrtico-subcorticals mediaria l’associació entre aquests mecanismes i la cognició. Els marcadors de disfunció endotelial es relacionen amb un perfil cognitiu diferent, que és característic tant de processos vasculars com neurodegeneratius. L’estudi III té com a objectiu valorar el possible ús dels biomarcadors de líquid cefaloraquidi pel diagnòstic de la MA. En concret, vàrem estudiar els perfils estructurals i cognitius en persones amb deteriorament cognitiu emprant punts de tall de líquid cefaloraquidi com a criteri d’agrupació. Els resultats mostren que pacients amb DC i amb nivells patològics de t-tau i p-tau al LCR (però no d’Aβ1-42) presenten un perfil cognitiu i estructural de MA. En conclusió, els resultats obtinguts en la present tesi suggereixen que, complementaris a l’observació clínica, els biomarcadors de LCR i plasma, així com els indicadors de morfologia cerebral podrien ser d’ús pel diagnòstic precoç del DCL i la demència.

The present dissertation, which can be framed in the fields of behavioural and psychiatric genetics, was aimed to study how early environmental factors such as parental negativity and childhood adversity, directly or in interaction with genetic factors account for psychopathological variation (subclinical and clinical psychiatric symptoms) in general populatiol including childhood behavioural problems, adult psychotic, depressive and anxious symptoms and their neuroimaging correlates. Furthermore, from the different studies included in this dissertation, additional research questions were also explored. The studies included in the thesis were based in singletons and twins samples. We found evidence indicating that child behaviour problems, anxious and depressive symptoms and psychotic experiences (PEs) were present in our samples drawn from the general population which is in agreement with a dimensional approach to psychopathology. Furthermore, using neuroimaging techniques, we were able to find structural brain correlates of vulnerability for anxiety and depression in a MZ twin sample from the general population. Also, psychotic experiences were associated with brain activation to facial emotion in this MZ twin sample. In regard to the specific environmental factors studied (parental negativity and childhood maltreatment), experiences occurring early in life showed to be associated to adolescent behaviour problems and adult psychotic experiences highlighting the enduring effects of exposure to childhood adversity. These results highlight the relevance of early adversity in the understanding of psychopathological features. Finally, our findings provide evidence of different ways through genes, environment and their interplay can modulate the final expression of the phenotype. Thus, while there is no doubt regarding that genes and environmental factors can have a direct influence in the phenotype, there is a gene-environment interdependence that must be considered when studying the etiology of complex characters. / Esta tesis doctoral, que se puede enmarcar en las áreas de la genética de la conducta y psiquiatría genética, se centró en el estudio del papel que desarrollan los factores ambientales, tales como la negatividad parental y la adversidad infantil, de manera directa o en interacción con factores genéticos, en la expresión de características psicopatológicas subclínicas en población general. La variación psicopatológica subclínica estudiada incluyó problemas de conducta en la infancia y el desarrollo de experiencias psicóticas y síntomas ansiosos y depresivos en la etapa adulta. Además se exploraron posibles correlatos de neuroimagen de estos fenotipos subclínicos. En cuanto a los resultados, se hallaron evidencias que indicaban que los problemas de conducta infantil, los síntomas ansiosos y depresivos y las experiencias psicóticas se distribuyen de forma continua en la población general. Estos hallazgos están de acuerdo con el enfoque dimensional a la psicopatología. Por otra parte, mediante el uso de técnicas de neuroimagen, se encontraron correlatos cerebrales estructurales para la vulnerabilidad para el desarrollo de síntomas ansiosos y depresivos en una muestra de gemelos monozigóticos (MZ) de la población general. Además, las experiencias psicóticas se asociaron con la activación del cerebro en respuesta a la emoción facial en esta muestra de gemelos MZ. En referencia a los factores ambientales específicos estudiados (negatividad parental y maltrato en la infancia), las experiencias que acontecen durante los primeros años de vida se asociaron con el desarrollo de problemas de conducta adolescentes y el riesgo a desarrollar experiencias psicóticas en la etapa adulta. Estos hallazgos ponen de relevancia los efectos a largo de la exposición a la adversidad durante la infancia. Por último, nuestros resultados ponen de manifiesto la compleja interacción y diferentes tipos de efectos mediantes los cuales los factores genéticos y ambientales ejercen sus influencias en la variabilidad fenotípica. En este sentido, variación en algunas variantes genéticas como el gen del BDNF o el gen de la COMT proporcionaban mayor vulnerabilidad neurobiológica a algunos individuos que habían estado expuestos a maltrato infantil y/o consumo de cannabis, factores de riesgo ampliamente reconocidos en psicosis.