Lobar Distribution of Lesion Volumes in Late-Life Depression: The Biomedical Informatics Research Network (BIRN)

Abstract

White matter hyperintense lesions on T2-weighted images are associated with late-life depression. Little work has been carried out examining differences in lesion location between elderly individuals with and without depression. In contrast to previous studies examining total brain white matter lesion volume, this study examined lobar differences in white matter lesion volumes derived from brain magnetic resonance imaging. This study examined 49 subjects with a DSM-IV diagnosis of major depression and 50 comparison subjects without depression. All participants were age 60 years or older. White matter lesion volumes were measured in each hemisphere using a semiautomated segmentation process and localized to lobar regions using a lobar atlas created for this sample using the imaging tools provided by the Biomedical Informatics Research Network (BIRN). The lobar lesion volumes were compared against depression status. After controlling for age and hypertension, subjects with depression exhibited significantly greater total white matter lesion volume in both hemispheres and in both frontal lobes than did control subjects. Although a similar trend was observed in the parietal lobes, the difference did not reach a level of statistical significance. Models of the temporal and occipital lobes were not statistically significant. Older individuals with depression have greater white matter disease than healthy controls, predominantly in the frontal lobes. These changes are thought to disrupt neural circuits involved in mood regulation, thus increasing the risk of developing depression.

White matter hyperintensities in late life depression: a systematic review

“…Consistent with this, several studies have observed a strong association between WMHs occurring in the orbitofrontal cortex and presence of LLD 53 54 56 – 58. However, the majority of studies of LLD employ rating scales that fail to incorporate lesion lateralisation or site.…”

“…Longitudinal studies are needed in order to clarify the mechanism underlying the link between hyperintensities and geriatric depression. This is an exciting avenue for future research, particularly when employing advanced imaging techniques, such as diffusion tensor imaging52 62 – 66 which is superior at assessing white matter integrity and detecting sites where hyperintensities may directly predispose to the development of depression 18 53. Delineation of the underlying mechanisms may have an impact on how we approach prevention and treatment of LOD and may lead to novel strategies aimed at managing geriatric depression 6…”

Brain grey matter volume alterations in late-life depression

“…52 Many studies have shown that the WMH associations with LLD occur mainly in subcortical regions and their frontal white matter projections. 44,[53][54][55][56] Diffusion tensor imaging studies have also shown microstructural white matter abnormalities in fronto-striatal-limbic networks, including the lateral to anterior and posterior cingulate cortices and the prefrontal, insular and parahippocampal regions, are associated with executive dysfunction in patients with LLD. 46,57 A grey matter volume increase was observed in the right lingual gyrus both in the pooled meta-analysis and the subgroup meta-analysis.…”

Assessment of Depression in Three Medically ill, Elderly Populations: Alzheimer's Disease, Parkinson's Disease, and Stroke

“…Namely, when compared to non-depressed elderly people, depressed elderly people are found to have lower frontal volumes and greater whole-brain high-intensity lesions (Kumar, Bilker, Jin, & Udupa, 2000). MacFall et al (2006) found that not only are frontal lobe lesion volumes greater in depressed elderly people, but there is also a trend for total and right parietal regions. Previous findings have also implicated frontal and parietal lesions, which extended into the occipital and temporal lobes in older individuals with greater levels of clinical depression, later onset of depression, and medical comorbidity (Artero et al, 2004).…”