Clinical manifestations of major depressive disorder (MDD) have been linked to structural and functional
alterations in fronto-limbic circuits and white matter microstructural abnormalities. However, little is known about how
brain pathological changes in volume and microstructure are related to illness progression throughout aging, including
course deterioration and treatment response. A comprehensive review of the literature regarding midlife- and late-onset
MDD was performed through PubMed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2014.
Eligible references included prospective studies in which structural neuroimaging assessments were performed in MDD
samples. The course of MDD may be associated with brain aging modifications, including hippocampal, amigdalar and
frontal volume reductions. White matter changes associated with MDD progression have been reported in the corpus
callosum, frontal and temporal regions and may be associated with poorer response to treatment. The data suggest that
both cortical and subcortical alterations may interact along the progression of MDD. Further knowledge brought by
neuroimaging studies, through the integration of multimodal techniques, may help to improve the accuracy of diagnosis,
disease monitoring and treatment response in MDD.
Keywords: Aging, cognition, depression, diffusion tensor imaging, neuroimaging, region of interest, tract based spatial
statistics, white matter lesions.
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