Biomarqueurs neuroanatomiques chez les individus à haut risque pour le trouble bipolaire
|Advisor:||Duchesne, Simon; Maziade, Michel|
|Abstract:||Bipolar disorder (BD) is a severe psychiatric disorder that affects a considerable proportion of humankind, and whose pathophysiology is still mostly unknown. Because relatives of patients with bipolar disorders are known to be at heightened risk for developing different types of mood disorders, the assessment of these individuals at an age that typically precedes disease onset is a relevant strategy for elucidating developmental and risk factors associated with an increased risk for BD and other affective disorders such as major depression. Magnetic resonance imaging (MRI) investigations in youths at high risk (HR) can help identify genetic vulnerabilities and potential risk markers of the earliest presence, nature, and extent of brain changes that occur during development of this illness and/or diseases associated with BD. This dissertation contributes to the body of research in this field by exploring brain morphology in asymptomatic adolescents and young adults at high risk of developing BD. In the first study (cf. Chapter II), we performed a meta-analysis of voxelbased morphometry (VBM) studies comparing grey and white matter in patients diagnosed with BD to healthy subjects, in order to better explain and understand the neuroanatomical changes related to the disease. This metaanalysis demonstrated the involvement of some gray and white matter regions, especially the frontal, cingulate, and parahippocampal cortices, the striatum, and connections located in the temporal lobe, the cingulate and insular cortices. In light of this study, we wished to explore the same regions in a group of asymptomatic subjects at high risk of developing the disease. Thus, in our second study (cf. Chapter III), we explored gray and white matter morphology using different techniques in eight children of BD patients from Québec compared with age- and sex-matched control individuals without family history of psychiatric disorders. Results reveal alterations in BD offsprings mainly located in cortical volumes and thicknesses in limbic, parietal, and frontal areas, as well as reduced white matter integrity in frontothalamic connections. With this study we confirmed the involvement of the frontal and parahippocampal cortices not only in bipolar disorder, but also as a possible endophenotype associated with a genetic risk of developing this illness. Finally, we investigated white matter (WM) integrity using diffusion tensor images (DTI) in a bigger sample of young subjects at HR of mood disorders recruited in Scotland. WM integrity differences between relatives of BD patients and controls were analyzed both at baseline and after longitudinal follow-up, at which point some high-risk subjects developed major depressive disorder. A reduced WM integrity in genetic high-risk subjects compared with controls was confirmed in this largest Scottish sample (cf. Chapter IV). Moreover, we demonstrated an association between WM integrity in different regions and sub-clinic symptoms of depression at baseline in HR subjects. Finally, we detected a progressive loss of WM integrity with time in both HR subjects and controls (cf. Chapter V). This dissertation provides compelling evidence that HR individuals present distinct neuroanatomical characteristics in both gray and white matter. The results have important theoretical and clinical implications, in that they contribute to clarifying the morphological features of this group and increasing our knowledge of the pathophysiology of BD in order to ameliorate the diagnostic process.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||24 April 2018|
|Collection:||Thèses et mémoires|
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