Abstract
The primary objective of our study was to examine the role of atrophy, high intensity lesions and medical comorbidity in the pathophysiology of major depressive disorder in the elderly (late-life MDD). Our sample was comprised of 51 patients with late-life MDD and 30 non-depressed controls. All subjects were scanned on 1.5 tesla magnetic resonance imaging scanner (MRI) and absolute and normalized measures of brain and lesion volumes were obtained and used for comparison between groups. Patients with MDD had significantly smaller frontal lobe volumes, together with larger whole brain lesion volumes when compared with controls (p < .05). Whole brain lesion volumes correlated significantly (r = 0.41, p = .006) with overall medical comorbidity. The odds ratio (OR) for existing MDD increases significantly with a decrease in frontal lobe volume and an increase in whole brain lesion volumes (p < .05). Our findings suggest that atrophy and high intensity lesions represent relatively independent pathways to late-life MDD. While medical disorders lead to neuropathological changes that are captured on MR imaging as high intensity signals, atrophy may represent a relatively autonomous phenomenon. These findings have broad implications for the pathophysiology of mood disorders and suggest that complementary neurobiological processes may lead to cumulative neuronal injury thereby predisposing to clinical depression.
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Acknowledgements
Supported by grants MH 55115 (to Dr Kumar) and MH 52129 (to Clinical Research Center) from NIMH. Presented in part at the 28th Annual Meeting of the Society for Neuroscience, Los Angeles, 1998.
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Appendix 1
Appendix 1
In Figure 2A, the temporal lobe region is drawn onto a 5-mm axial T2 image. The region delineated is representative of temporal lobe drawings for all slices inferior to the one shown. In Figure 2B, the frontal and temporal lobe regions are drawn on a slice located 1 cm superior to that shown in A The line used to delineate the posterior temporal border is depicted with dashes from the anteriormost tip of the contralateral cerebral peduncle to the anteromedialmost tip of the cerebellum. The frontal and temporal lobe regions drawn onto slices located 1 cm and 2 cm superior to that shown in B are depicted in C and D, respectively. All frontal regions drawn on slices superior to the one shown in D used the same posterior boundary. It should be noted that all regions drawn encompass tissue to be further segmented into brain and CSF volumes.
The boundaries of the frontal and temporal lobes from the inferior to the superior slices of the brain. C, cerebellum; cn, caudate nucleus; cp, cerebral peduncle; F, frontal region; d, diencephalon; if, interhemispheric fissure; mca, middle cerebral artery; p, pons; sf, sylvian fissure; T, temporal region
Neuroradiologic evaluation of MRI's. Prior to regional measurement, brains were realigned in three dimensions using the software package PETVIEW 1.1 and resliced along the AC-PC axis to standardize for differences in head tilt during image acquisition. Resliced images were then imported into another computer software package (Kohn et al., 1991) modified to accommodate regional analysis. The borders of the frontal and temporal lobes were drawn by investigators working with a neuroradiologist using standardized boundaries.
In the inferiormost slices, the temporal lobe did not share common lateral or anterior borders with other structures and was easily outlined. The posteromedial temporal lobe border was formed by the pons and cerebellum (Figure 2A). At the level of the midbrain, borders of the frontal lobe were drawn along the interhemispheric fissure and followed the middle cerebral artery through the suprasellar cistern (Figure 2B). The temporal lobe was separated from adjacent frontal regions by the Sylvian fissure within which runs the middle cerebral artery. The amygdala and hippocampus were included within the temporal lobe, and the midbrain structures were excluded (Figure 2B). The posterior temporal lobe was delineated by a line extending from the anteriormost tip of the contralateral cerebral peduncle to the anteromedialmost tip of the cerebellum (the dashed line in Figure 2B).
Above the level of the mammillary bodies, the posterior border of the frontal lobe was delineated by a horizontal line that extended from the anteromedial-most aspect of the Sylvian fissure to midline (Figure 2C). The medial borders of the temporal lobe were the Sylvian fissure and structures of the diencephalon (Figure 2C, D). A horizontal line, extending from the posteriormost tip of the posterior fossa to the lateral cortical perimeter, delineated the posterior temporal lobe (Figure 2C). The posterior border for the remaining superior slices containing frontal lobe was delineated in the slice immediately inferior to the crossing of the splenium of the corpus callosum (Figure 2D). A line defined by the anteriormost aspect of the caudate was drawn from the midline to the Sylvian fissure. This slice was also the most superior location at which temporal lobe borders were drawn. Adapted from Cowell et al, J Neuroscience, 1994
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Kumar, A., Bilker, W., Jin, Z. et al. Atrophy and High Intensity Lesions. Neuropsychopharmacol 22, 264–274 (2000). https://doi.org/10.1016/S0893-133X(99)00124-4
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DOI: https://doi.org/10.1016/S0893-133X(99)00124-4
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