Abstract
The large majority of structural MRI studies of major depressive disorder (MDD) investigated volumetric changes in chronic medicated patients in whom course of illness and treatment effects may impact anatomic measurements. Further, in few studies, separate measurements of cortical thickness and surface area have been performed that reflect different neurobiological processes regulated by different genetic mechanisms. In the present study, we investigated both cortical thickness and surface area in first-episode, treatment-naïve, mid-life MDD to elucidate the core pathophysiology of this disease and its early impact on the brain. We observed increased cortical thickness in the right hemisphere, including medial orbitofrontal gyrus, pars opercularis, rostral middle frontal gyrus and supramarginal gyrus. Increased thickness of rostral middle frontal gyrus was negatively related with depression severity on the Hamilton Depression Rating Scale. Furthermore, MDD patients showed significantly increased associations in cortical thickness measurements among areas where increased cortical thickness was observed. Analysis of pial area revealed a trend toward increased surface area in the left parahippocampal gyrus in MDD. To permit comparison of our data with those of previous gray matter volume studies, voxel-based morphometry was performed. That analysis revealed significantly increased gray matter volume in left paracentral lobule, left superior frontal gyrus, bilateral cuneus and thalamus which form limbic-cortico–striato–pallido–thalamic loops. These changes in first-episode, treatment-naïve, mid-life MDD patients may reflect an active illness-related cortical change close to illness onset, and thus potentially provide important new insight into the early neurobiology of the disorder.
Highlights
Though major depressive disorder (MDD) ranks as the leading cause of years lived with disability among all diseases,[1] the pathogenesis and pathophysiological processes of this illness are not well understood
No region with significantly decreased cortical thickness was found in MDD patients (Figure 1 and Table 2)
Controls showed no significant correlation among these areas except for a positive correlation between right medial orbitofrontal gyrus and right rostral middle frontal gyrus (r = 0.35, P = 0.019)
Summary
Though major depressive disorder (MDD) ranks as the leading cause of years lived with disability among all diseases,[1] the pathogenesis and pathophysiological processes of this illness are not well understood. Most previous structural studies of brain anatomy in MDD investigated volumetric changes in chronic medicated patients. These studies most commonly reported reduced gray matter volume in regions including anterior cingulate,[2,3] orbitofrontal cortex,[2,3,4] dorsal anterolateral and ventrolateral prefrontal cortex, precuneus and inferior parietal lobule.[3] Two meta-analyses reported smaller volumes of the basal ganglia, thalamus, hippocampus, anterior cingulate and orbitofrontal cortex in MDD.[5,6] In addition, three studies[7,8,9] measured cortical thickness in elderly MDD patients and one of these studies[9] found significantly decreased cortical thickness. Another study found significantly thinner posterior cingulate cortex in non-remitters with MDD than in remitters.[12]
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