ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Genetic and environmental factors interact to influence vulnerability for internalizing psychopathology, including Major Depressive Disorder (MDD). The mechanisms that account for how environmental stress can alter biological systems are not yet well understood yet are critical to develop more accurate models of vulnerability and targeted interventions. Epigenetic influences, and more specifically, DNA methylation, may provide a mechanism by which stress could program gene expression, thereby altering key systems implicated in depression, such as frontal-limbic circuitry and its critical role in emotion regulation. This thesis investigated the role of environmental factors from infancy and throughout the lifespan affecting the serotonergic (5-HT) system in the vulnerability to and treatment of depression and anxiety and potential underlying DNA methylation processes. First, we investigated the contributions of additive genetic vs. environmental factors on an early trait phenotype for depression (negative emotionality) in infants and their stability over time in the first 2 years of life. We provided evidence of the substantial contributions of both genetic and shared environmental factors to this trait, as well as genetically- and environmentally- mediated stability and innovation. Second, we studied how childhood environmental stress is associated with peripheral DNA methylation of the serotonin transporter gene, SLC6A4, as well as long-term trajectories of internalizing behaviours. There was a relationship between childhood psychosocial adversity and SLC6A4 methylation in males, as well as between SLC6A4 methylation and internalizing trajectory in both sexes. Third, we investigated changes in emotion processing and epigenetic modification of the SLC6A4 gene in depressed adolescents before and after Mindfulness-Based Cognitive Therapy (MBCT). The alterations from pre- to post-treatment in connectivity between the ACC and other network regions and SLC6A4 methylation suggested that MBCT may work to optimize the connectivity of brain networks involved in cognitive control of emotion as well as also normalize the relationship between SLC6A4 methylation and activation patterns in frontal-limbic circuitry. Our results from these three studies strengthen the theory that environmental influences are critical in establishing early vulnerability factors for MDD, driving epigenetic processes, and altering brain processes as an individual undergoes treatment, or experiences relapse.

Comorbid Migraine in Major Depressive Disorder Suggests a Subgroup Related to Bipolar Disorder

Aims: Previous small-scale studies suggest presence of migraine in major depressive disorder (MDD) is associated with specific clinical characteristics that may overlap with those of bipolar disorder. We aimed to compare a broad range of characteristics in participants who have MDD with and without migraine, and to explore possible similarities between those characteristics associated with the presence of migraine in MDD and those in bipolar disorder in a large UK sample. Methods: Lifetime and episodic clinical characteristics and affective temperaments in DSM-IV MDD with (n=134) and without (n=218) migraine were compared. Characteristics associated with the presence of migraine were then compared with a sample of participants with DSM-IV bipolar disorder (n=407). All participants were recruited into the Bipolar Disorder Research Network (www.bdrn.org). Results: The presence of migraine in MDD was associated with female gender (76.9% vs 56.9%, p<0.001), younger age of onset (23 vs 27 years, p=0.002), history of attempted suicide (38.3% vs 22.7%, p=0.002), and more panic/agoraphobia symptomatology (6 vs 4, p<0.001). Female gender (OR=2.44, p=0.006) and younger age of onset (OR=0.97, p=0.013) remained significant in a multivariate model. These clinical characteristics were not significantly different to those of our participants with bipolar disorder. Conclusions: The presence of migraine in MDD delineates a subgroup of individuals with a more severe illness course. The clinical presentation of this subgroup more closely resembles that of bipolar disorder than that of MDD without migraine. The presence of migraine in major depression may be a marker of a specific subgroup that could be useful in future research.

Polygenic Interactions with Environmental Adversity in the Aetiology of Major Depressive Disorder

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

Seasonality Shows Evidence for Polygenic Architecture and Genetic Correlation With Schizophrenia and Bipolar Disorder

OBJECTIVE: To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. METHOD: Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality. RESULTS: The most significant association was with rs11825064 (P = 1.7 × 10⁻⁶, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in log-transformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10⁻³), and no evidence for overlap in risk was detected between MDD and seasonality. CONCLUSIONS: Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia.

Bisphenol A alters transcript levels of biomarker genes for major depressive disorder in vascular endothelial cells and colon cancer cells

Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans.

Construyendo Perfiles Virtuales Mediante el Procesamiento de Eventos Complejos

A medida que se incrementa el nímero de dispositivos inteligentes, el esfuerzo requerido para adaptarlos a las necesidades de cada usuario también crece. Asimismo, el proceso de adaptación de un dispositivo al contexto de un usuario es todavía un proceso muy manual. A pesar de que en los últimos años han surgido algunas propuestas centradas en obtener la información contextual de los usuarios para crear sus perfiles virtuales, se necesitan soluciones novedosas que permitan crear perfiles más completos, que sean utilizados por los dispositivos inteligentes para adaptarse automáticamente a las necesidades de sus usuarios, redundando en una mayor exactitud de la adaptación. En este artículo se propone la integración del modelo computacional People as a Service (PeaaS) con el procesamiento de eventos complejos (CEP) para la creación en tiempo real de perfiles virtuales complejos desde el propio dispositivo móvil y la compartición de estos como servicios para el resto de sistemas y dispositivos. Además, se evalúa esta integración en un caso de estudio sobre Alzheimer. Los resultados confirman que el uso de la tecnología CEP para la identificación de información contextual compleja es posible.

Towards person-centered neuroimaging markers for resilience and vulnerability in Bipolar Disorder

Improved clinical care for Bipolar Disorder (BD) relies on the identification of diagnostic markers that can reliably detect disease-related signals in clinically heterogeneous populations. At the very least, diagnostic markers should be able to differentiate patients with BD from healthy individuals and from individuals at familial risk for BD who either remain well or develop other psychopathology, most commonly Major Depressive Disorder (MDD). These issues are particularly pertinent to the development of translational applications of neuroimaging as they represent challenges for which clinical observation alone is insufficient. We therefore applied pattern classification to task-based functional magnetic resonance imaging (fMRI) data of the n-back working memory task, to test their predictive value in differentiating patients with BD (n=30) from healthy individuals (n=30) and from patients' relatives who were either diagnosed with MDD (n=30) or were free of any personal lifetime history of psychopathology (n=30). Diagnostic stability in these groups was confirmed with 4-year prospective follow-up. Task-based activation patterns from the fMRI data were analyzed with Gaussian Process Classifiers (GPC), a machine learning approach to detecting multivariate patterns in neuroimaging datasets. Consistent significant classification results were only obtained using data from the 3-back versus 0-back contrast. Using contrast, patients with BD were correctly classified compared to unrelated healthy individuals with an accuracy of 83.5%, sensitivity of 84.6% and specificity of 92.3%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their relatives with MDD, were respectively 73.1%, 53.9% and 94.5%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their healthy relatives were respectively 81.8%, 72.7% and 90.9%. We show that significant individual classification can be achieved using whole brain pattern analysis of task-based working memory fMRI data. The high accuracy and specificity achieved by all three classifiers suggest that multivariate pattern recognition analyses can aid clinicians in the clinical care of BD in situations of true clinical uncertainty regarding the diagnosis and prognosis.

El merchandising de las marcas de distribución vs. marcas de fabricantes, en productos de alimentación de la Comunidad Autónoma de Madrid

El presente trabajo se centra en el estudio de ciertos elementos de Marchandising relacionados con la pujanza que en los últimos años han conseguido las marcas propias de la Distribución y sus efectos sobre las marcas de fabricantes, fundamentalmente, líderes. OBJETIVOS Y RESULTADOS: Durante la década analizada, crecieron las Marcas Privadas (MDD) en alimentación y apareció la segunda generación de Marcas Propias (Marcas de Primer Precio: MPP) La bibliografía de Marketing es escasa en referencias al Merchandising y, menos con métodos cuantitativos. De aquí nuestra motivación para abordar este tema que consideramos de gran importancia. Por todo ello nos hemos propuesto cubrir los siguientes objetivos, aunque obviamente se detallan en las hipótesis a corroborar son los siguientes: • Espacio dedicado en el lineal de las MDD vs MF • Situación en el lineal de las MDD vs MF • Comparación de actividades promocionales y sus clases entre las MDDs y las MFs • Comparación de calidad de envases de las MDDs vs MFs • Finalmente hemos querido modernizar y actualizar ciertos contenidos académicos. HIPÓTESIS A CORROBORAR HIPÓTESIS TEÓRICA: Las enseñas con marcas de distribución, con el objetivo de incrementar el margen bruto de los productos con estas marcas, tienden a optimizar las acciones de marketing de sus marcas vs. las marcas líderes, en sus mismos mercados. HIPÓTESIS BÁSICAS: H1.- Las Marcas de Distribuidor gozan de, al menos, igual longitud de lineal que las marcas de fabricante líderes de su categoría de producto... NOTA 520 8 The current research focuses on certain Merchandising elements related to the push that in the latest years have gotten distribution private labels and its effects over manufactureŕs brand, mainly, leaders. RESEARCH OBJECTIVES AND OUTCOMES During the analyzed decade, the explosion of the Private Brands (PB) happened in the food market of Spain. In this period of time the second generations of Private Brands (First Price Brands) were launched. In Marketing bibliography there is only a few Merchandising references. And among the latter, there are even fewer when it comes to quantitative publications. This is the reason why the target of this research is mainly quantitative. Due to these considerations, the objectives to cover (detailed in the hypothesis to corroborate) have been: Share of shelf of PB vs MB Shelf position of PB vs MB Comparison of PB́s packaging vs MB Promotional activities and types of PB vs MB Below the Line And also an update of certain academic content The main statements investigated are based on the following hypothesis: THEORETICAL ASSUMPTION: Distributors that own private brands, with the objective to increase the gross margin of these brands, tend to optimize Marketing tactics of their own brands vs. manufactureŕs brands...

Propuesta de un modelo de desarrollo de las marcas de distribución en España

El desarrollo de las marcas de distribución (MDD) a expensas de las marcas de fabricante (MF) ha sido un cambio importante en la industria de bienes de gran consumo mundial en las pasadas décadas. Particularmente importante en Europa, este fenómeno ha sido ampliamente investigado para entender los factores explicativos de su éxito, identificándose históricamente diferentes variables como palancas del crecimiento de la cuota de mercado de la MDD. España es el país europeo con la segunda mayor cuota de MDD. Se puede considerar un mercado maduro y el reciente entorno económico desfavorable ha podido introducir nuevos patrones de consumo en los consumidores. Por tanto, hay un interés genuino en revisar la validez de las variables clásicas como variables explicativas de la cuota de MDD en este contexto. Este estudio es original debido al análisis mensual de un número considerable de variables y a la inclusión de variables que no han sido poco comprobadas anteriormente. Además, el periodo de estudio introduce el aspecto de la crisis económica y de consumo como un elemento potencial de cambio respecto al pasado. Esta investigación tiene el objetivo de verificar qué variables influyen en la cuota de mercado de las MDD en los mercados de gran consumo en España...

The Comparative Effectiveness of EEG Biomarkers in Antidepressant Response and Illness Prediction in Major Depressive Disorder

Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2016-08-27 00:55:35.782

ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Thesis (Ph.D, Psychology) -- Queen's University, 2016-10-04 17:37:07.888