Major depression is a prevalent mental disorder with a high risk of recurrence and unsatisfactory treatment response, which associates high rates of disability, psychosocial impairment, excess of morbidity and mortality and high healthcare costs. Some evidence suggests that brain changes occurring during depressive episodes may leave residual traces which progressively increase the risk of refractoriness and vulnerability to further relapses. In recent decades, development and implementation of neuroimaging techniques have help to identify at least part of the underlying neuroanatomical and functional abnormalities in depression, although alterations related to clinical course have been less explored. The aim of the current thesis was to gain knowledge about the neural substrate of recurrence and chronicity, ie those neuroimaging abnormalities that would be associated with relapse or treatment failure, even those that may accumulate along the course of the illness interfering with clinical recovery. Studies were based on two particular techniques: Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging. This thesis is composed by three articles published in international journals indexed on most popular scientific databases [1-3]. The first two works assess neurochemical alterations associated with refractoriness and history of recurrences in ventromedial prefrontal cortex (vmPFC) and hippocampus, two keys areas in the pathophysiology of affective disorders, sensitive to the potentially harmful effects of chronic stress. The third study evaluates changes in the white-matter microstructure in the cortico-cortical and cortico-subcortical pathways, including the fronto- limbic connectivity. Studies, based on representative samples of a wide spectrum of disease severity, show changes in glutamate-glutamine and other metabolites levels within vmPFC and hippocampus and widespread abnormalities of white matter microstructure in depressive patients clearly overrepresented among those with worst clinical response, history of previous episodes or longer illness duration. Findings are highly suggestive of the neurotoxic potential of depressive states and warrant longitudinal studies to confirm the possible progression of these markers in subgroups of patients with the worst prognosis over the course of the illness.
|Date of Award||11 Jul 2014|
|Supervisor||Enric Alvarez Martinez (Director) & Maria Jesus Portella Moll (Director)|