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Dysthymic Disorder Case Study

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Dysthymic Disorder (DD) is a chronic, debilitating depressive illness characterized by depressed mood for 2 or more years1. Pathophysiology of DD, however, remains poorly understood as few studies have assessed brain abnormalities in DD. Patients with DD have symptoms that fall along a continuous spectrum for unipolar depression and respond similarly to medication2 as those with Major Depressive Disorder (MDD); therefore, abnormalities in brain structure, function, and metabolism in DD previously have been inferred from those in MDD. Brain metabolism and how it is altered in illness can be quantitatively assessed in vivo using Magnetic Resonance Spectroscopy (MRS), a noninvasive technique that quantifies several endogenous neurochemicals, …show more content…

Although single voxel MRS generates spectra with high signal-to-noise ratio, a single MRS voxel cannot be placed in a homologous brain region because of differing brain size and gray matter gyration across individuals. Furthermore, an MRS voxel across participants will contain differing amounts of gray and white matter, with each tissue type containing differing amounts of metabolites will contribute differentially to MRS signal. Therefore, variability in placement and amounts of differing tissue types increases variability in metabolite levels ascertained from single voxel MRS, decreasing statistical power to detect abnormalities in metabolite levels. Second, extant studies often used a case-control design where MR data were acquired only once in each participant. These studies therefore can assess only associations, but not causal relations, between metabolite levels and mechanism of illness. Third, although treatment response and symptoms across unipolar depression fall along a continuum, abnormalities in brain structure, function, and metabolism in DD may differ from those in MDD. Brain abnormalities in DD therefore cannot be inferred from studies of MDD. For example, we showed23 that individuals at high risk for MDD compared with those at low risk had thinner cortex in the right hemisphere of the brain, whereas patients with DD had thicker cortex across large portions of the brain24. Similarly, metabolic abnormalities in

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