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You searched for +publisher:"McGill University" +contributor:("Gustavo Turecki"). Showing records 1 – 3 of 3 total matches.

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McGill University

1. Ju, Chelsey. Differential DNA methylation as a predictor biomarker of antidepressant response in patients with major depressive disorder.

Degree: MS, Integrated Program in Neuroscience, 2018, McGill University

Major depressive disorder (MDD) is a severe and debilitating disease that is primarily treated with antidepressants. However, many patients fail to respond to medication, even after multiple attempts. Given the lack of objective clinical diagnostic and treatment guidelines, a predictor biomarker for antidepressant response (ADR) would largely improve clinical practice for treating MDD, and decrease the time required to effectively treat patients.In addition to genetic factors, environmental factors are also associated with MDD etiology and treatment efficacy. Epigenetic mechanisms better reflect the interaction between genetic and environmental induced effects through chromatin structure modifications, without affecting the DNA sequence directly. An epigenetic biomarker would thus be more sensitive and functional in accounting for the multifactorial basis of treatment response variation in patients. DNA methylation is the best-known type of epigenetic modification, and has been studied in the context of treatment response. However, current studies are based on hypothesis driven approaches, and no genome wide investigations have been made.This thesis aims to identify predictive, functional biomarkers for ADR using a novel genome wide method from peripheral blood samples. Firstly, we observed multiple significantly differentially methylated positions (DMPs) from microarray-based data. When selecting DMPs for validation and replication, we selected DMPs located in differentially expressed genes identified from our genome wide expression analysis. This revealed three DMPs of interest that were validated and partially replicated. We also performed functional annotation analysis which provided further functional perspectives as well. Collectively, this thesis discusses our exploratory findings of new candidates for predicting ADR, along with an overview of possible molecular mechanisms that characterize ADR.

La dépression majeure est un trouble mental sévèrement incapacitant, traité principalement pharmacologiquement par les antidépresseurs. Leur efficacité est cependant relative, puisque près d'un tiers des patients sous traitement n'atteignent pas la rémission et cela même après plusieurs traitements. Compte tenu de l'absence de critères objectifs et systématiques pour établir un diagnostic et pour définir une stratégie thérapeutique adaptée, la découverte de biomarqueurs prédictifs de la réponse aux antidépresseurs faciliterait considérablement la prise en charge clinique des patients vers la rémission.Au-delà des facteurs génétiques, les facteurs environnementaux contribuent aussi grandement à l'étiologie de la dépression et la variabilité dans la réponse aux antidépresseurs. Dans ce contexte, les mécanismes épigénétiques sont des indicateurs pertinents de l'effet de l'environnement sur nos gènes. Ces mécanisme modifient l'architecture de la chromatine et donc l'expression de nos gènes sans pour autant affecter leur séquence ADN.Pour cette raison, un biomarqueur épigénétiques sera plus à même de prendre en compte…

Advisors/Committee Members: Gustavo Turecki (Internal/Supervisor).

Subjects/Keywords: Neuroscience

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Ju, C. (2018). Differential DNA methylation as a predictor biomarker of antidepressant response in patients with major depressive disorder. (Masters Thesis). McGill University. Retrieved from http://digitool.library.mcgill.ca/thesisfile160916.pdf

Chicago Manual of Style (16th Edition):

Ju, Chelsey. “Differential DNA methylation as a predictor biomarker of antidepressant response in patients with major depressive disorder.” 2018. Masters Thesis, McGill University. Accessed June 19, 2019. http://digitool.library.mcgill.ca/thesisfile160916.pdf.

MLA Handbook (7th Edition):

Ju, Chelsey. “Differential DNA methylation as a predictor biomarker of antidepressant response in patients with major depressive disorder.” 2018. Web. 19 Jun 2019.

Vancouver:

Ju C. Differential DNA methylation as a predictor biomarker of antidepressant response in patients with major depressive disorder. [Internet] [Masters thesis]. McGill University; 2018. [cited 2019 Jun 19]. Available from: http://digitool.library.mcgill.ca/thesisfile160916.pdf.

Council of Science Editors:

Ju C. Differential DNA methylation as a predictor biomarker of antidepressant response in patients with major depressive disorder. [Masters Thesis]. McGill University; 2018. Available from: http://digitool.library.mcgill.ca/thesisfile160916.pdf


McGill University

2. Crapper, Liam. «In vitro» modelling of Lesch-Nyhan Disease.

Degree: PhD, Integrated Program in Neuroscience, 2018, McGill University

Lesch-Nyhan Disease (LND) is a rare neurodevelopmental disorder characterized by metabolic symptoms including the accumulation of uric acid crystals in the urine, hyperuricemia, and gout, and neurological symptoms including severe dystonia, intellectual disability, and chronic self-harming behaviours. The causal gene, HPRT1, has been known since 1967 but, despite 50 years of research, the mechanisms and pathways through which HPRT1 mutations cause the neurological symptoms of LND remain unknown. A primary challenge hindering progress in LND research is that traditional approaches to disease modelling have not been very effective. Many in vitro and in vivo models have been used to study LND, but each comes with substantial limitations and studies in different models have yielded at times contradictory results.This work presents the development and transcriptome profiling of three novel models of LND using short hairpin RNA knockdowns (shHPRT) in immortalized human midbrain progenitors, and patient induced pluripotent stem cell-derived forebrain-like neural (fNPCs) and midbrain-like neural progenitors (mdNPCs). These are the first human neuronal models of LND and the largest and most comprehensive transcriptomic datasets available for LND research. Using a combination of bioinformatics, targeted validation, and functional assessments, we have shown cell-type specific alterations to adenosine neurotransmission and increases of the expression of mitochondrial genes. These changes are not found in the brains of HPRT knockout mice, and emphasize the need for species and cell-type accurate models of neurodevelopmental disorders. 

Le syndrome de Lesch-Nyhan (LND) est un trouble neurodéveloppemental rare caractérisé par des symptômes métaboliques incluant l'accumulation de cristaux d'acide urique dans l'urine, l'hyperuricémie et la goutte et des symptômes neurologiques incluant dystonie sévère, déficience intellectuelle et comportements autodestructeurs chroniques. Le gène causal, HPRT1, est connu depuis 1967 mais, malgré 50 années de recherche, les mécanismes et les voies par lesquels les mutations HPRT1 causent les symptômes neurologiques de LND restent inconnus. Un obstacle principal à la progression de la recherche sur le LND est que les approches traditionnelles de la modélisation des maladies n'ont pas été très efficaces. De nombreux modèles in vitro et in vivo de LND ont été utilisés pour étudier le LND, mais chacun présente des limites importantes et des études menées dans différents modèles ont donné des résultats parfois contradictoires.Ce travail présente le développement et le profilage transcriptomique de trois nouveaux modèles de LND utilisant des knockdowns de petit ARN en épingle à cheveux (shHPRT) dans des progéniteurs du mésencéphale humain immortalisés, et des progéniteurs neuraux du cerveau antérieur (fNPCs) et mésencéphaliques mdNPCs) dérivés de cellules souches pluripotentes dérivés de patients. Ce sont les premiers modèles neuronaux humains de LND et les ensembles de données transcriptomiques les…

Advisors/Committee Members: Carl Ernst (Supervisor1), Gustavo Turecki (Supervisor2).

Subjects/Keywords: Neuroscience

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Crapper, L. (2018). «In vitro» modelling of Lesch-Nyhan Disease. (Doctoral Dissertation). McGill University. Retrieved from http://digitool.library.mcgill.ca/thesisfile160857.pdf

Chicago Manual of Style (16th Edition):

Crapper, Liam. “«In vitro» modelling of Lesch-Nyhan Disease.” 2018. Doctoral Dissertation, McGill University. Accessed June 19, 2019. http://digitool.library.mcgill.ca/thesisfile160857.pdf.

MLA Handbook (7th Edition):

Crapper, Liam. “«In vitro» modelling of Lesch-Nyhan Disease.” 2018. Web. 19 Jun 2019.

Vancouver:

Crapper L. «In vitro» modelling of Lesch-Nyhan Disease. [Internet] [Doctoral dissertation]. McGill University; 2018. [cited 2019 Jun 19]. Available from: http://digitool.library.mcgill.ca/thesisfile160857.pdf.

Council of Science Editors:

Crapper L. «In vitro» modelling of Lesch-Nyhan Disease. [Doctoral Dissertation]. McGill University; 2018. Available from: http://digitool.library.mcgill.ca/thesisfile160857.pdf


McGill University

3. Ding, Yang. Neuroimaging of suicidal behaviour: a collection of recent studies in suicide attempters and relatives.

Degree: PhD, Integrated Program in Neuroscience, 2018, McGill University

This thesis presents a series of studies exploring the neurocognitive aspects of suicidal vulnerability using neuroimaging in both suicide attempters and first degree biological relatives of suicide completers. Through a systematic literature review, we demonstrated the association between suicidal acts and structural and functional alterations in several brain regions. We then examined structural neuroimaging measures in the prefrontal cortex of a large sample of suicide attempters and highlighted significant alterations in the left ventrolateral prefrontal cortex, independently from mood disorders. Moreover, we showed that the volume of the nucleus accumbens was negatively correlated with the lethality of previous suicidal acts, which suggests that this region may modulate the way suicidal acts are completed. We then used functional neuroimaging and the classical Go-NoGo task to examine cognitive inhibition among suicide attempters. Our results suggest that cognitive control deficits within suicide attempters, associated with the activation of the inferior frontal gyrus, thalamus, orbitofrontal cortex and parietal cortex, are more likely to be state-related than traits. Moreover, we examined relatives of suicide completers using a battery of cognitive measures and neuroimaging. We found decision-making deficits, but no cognitive control deficits, in suicide relatives who themselves never attempted suicide compared to patient relatives with no family history of suicidal acts and to healthy controls. These results suggest that risky decision-making could be a transmitted trait within families while normal cognitive control could be protective against suicide in these individuals. Furthermore, we showed that risky decision-making in sucide relatives was associated with significant reduction in ventromedial prefrontal cortex activity during decision-making and increased activity in precuneus during choice processing. Finally, both outcome processing during decision-making and angry faces processing (a proxy for social threat) were associated with altered activity in the cerebellum among suicide relatives. Overall, our findings strongly support a significant role for the ventral (both medial and lateral) prefrontal cortex, but they also highlight a network of brains regions beyond the prefrontal cortex. Moreover, they underline the importance and potential heritability of risky decision-making in suicidal vulnerability and the possibility that some cognitive deficits may be states while others are traits. These new findings expand our knowledge and allow us to propose an updated neurocognitive model of suicide.

Cette thèse présente une série d'études explorant les aspects neurocognitifs de la vulnérabilité suicidaire grâce à l'imagerie cérébrale ches des suicidants et des apparentés au premier degré biologique de suicidés. Une revue systématique de la littérature nous a permis de montrer une association entre les actes suicidaires et des modifications structurelles et fonctionnelles dans plusieurs régions du cerveau.…

Advisors/Committee Members: Fabrice Jollant (Supervisor1), Gustavo Turecki (Supervisor2).

Subjects/Keywords: UMIC code is not required - UMIC code is not required

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Ding, Y. (2018). Neuroimaging of suicidal behaviour: a collection of recent studies in suicide attempters and relatives. (Doctoral Dissertation). McGill University. Retrieved from http://digitool.library.mcgill.ca/thesisfile150771.pdf

Chicago Manual of Style (16th Edition):

Ding, Yang. “Neuroimaging of suicidal behaviour: a collection of recent studies in suicide attempters and relatives.” 2018. Doctoral Dissertation, McGill University. Accessed June 19, 2019. http://digitool.library.mcgill.ca/thesisfile150771.pdf.

MLA Handbook (7th Edition):

Ding, Yang. “Neuroimaging of suicidal behaviour: a collection of recent studies in suicide attempters and relatives.” 2018. Web. 19 Jun 2019.

Vancouver:

Ding Y. Neuroimaging of suicidal behaviour: a collection of recent studies in suicide attempters and relatives. [Internet] [Doctoral dissertation]. McGill University; 2018. [cited 2019 Jun 19]. Available from: http://digitool.library.mcgill.ca/thesisfile150771.pdf.

Council of Science Editors:

Ding Y. Neuroimaging of suicidal behaviour: a collection of recent studies in suicide attempters and relatives. [Doctoral Dissertation]. McGill University; 2018. Available from: http://digitool.library.mcgill.ca/thesisfile150771.pdf

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