Atrophy and High Intensity Lesions Complementary Neurobiological Mechanisms in Late-Life Major Depression

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) Depression is one of the most common mental disorders in the elderly (Alexopolous et al. 1988;Beck and Koenig 1996;Blazer et al. 1987;Blazer 1989Blazer , 1994Koenig et al. 1993;Oxman et al. 1987;Parmalee et al. 1989;Ruegg et al. 1988;Sherbourne et al. 1994). The prevalence of major depressive disorder (MDD) is estimated to be approximately 1-2 percent in community settings and strikingly higher in inpatient and long term care settings (Blazer et al. 1987;Koenig et al. 1993;Parmalee et al. 1989). The prevalence of other clinically significant forms of depression, that do not meet the severity criteria for MDD, lies between 5 and 15 percent in all major clinical settings (Beck and Koenig 1996;Blazer et al. 1987, Blazer 1994Parmalee et al. 1989). Anatomical and physiological neuroimaging approaches have been utilized to study the neurobiological correlates of MDD and minor depression in the elderly (Coffey et al. 1990;Coffey et al. 1993;Greenwald et al. 1996;Krishnan et al. 1988;Krishnan 1993;Kumar et al. 1997a;Lesser et al. 1994;Sackheim et al. 1993;Sheline et al. 1996). Glucose hypometabolism and Lesser et al. 1994;Sackheim et al. 1993). Using magnetic resonance imaging (MRI), investigators have demonstrated neuroanatomical abnormalities including smaller focal brain volumes and larger high intensity lesion volumes in patients with both late-life major and minor depression when compared with non-depressed controls (Coffey et al. 1990;Coffey et al. 1993;Greenwald et al. 1996;Krishnan et al. 1988;Krishnan 1993;Kumar et al. 1997aKumar et al. , 1997bKumar et al. , 1998Sheline et al. 1996).Despite these observations, the precise nature and extent of the neuroanatomical changes in elderly patients with MDD remains unresolved (Jeste et al. 1988;Morris and Rapoport 1990).Late-life MDD is also consistently associated with medical comorbidity (Berkman et al 1986;Gierz and Jeste 1993;Katz et al. 1994;Katz 1996;Lacro and Jeste 1994;Rodin and Voshart 1986). A broad spectrum of medical disorders including cardiovascular, musculoskeletal, gastrointestinal, pulmonary and metabolic disturbances are associated with both major and minor forms of depression (Alexopolous et al. 1988;Katz et al. 1994;Koenig et al. 1993;Lacro and Jeste 1994). Despite this association, the relationship between neuroanatomical abnormalities and medical disorders in late-life and their relative contributions to the pathophysiology of mood disorders remain unknown.In an earlier report, we demonstrated that the odds of developing MDD in late-life increased with overall medical burden and larger whole brain cerebrospinal fluid (CSF) volume (Kumar et al. 1997a). However, only global measures ...

Temporal Lobe Atrophy and White Matter Lesions are Related to Major Depression over 5 years in the Elderly

“…Cross-sectional associations between WMLs and depression have been shown repeatedly, especially for MRI and mainly from clinical studies (Greenwald et al, 1998;Ikram et al, 2010;Kumar et al, 2000;Kumar et al, 2002), although not all studies support this association (Rainer et al, 2006;Skoog et al, 1994). Our finding that WMLs preceded major depression is in agreement with three previous longitudinal studies using MRI (Godin et al, 2008;Steffens et al, 2002;Teodorczuk et al, 2007).…”

“…Our findings support the hypothesis that brain atrophy and WMLs represent relatively independent and complementary pathways to the development of major depression in the elderly (Kumar et al, 2000;Kumar et al, 2002). The only previous study that has explored this hypothesis is a clinical cross-sectional study, and depression was related to frontal but not temporal lobe atrophy (Kumar et al, 2000).…”

“…Regarding cerebrovascular disease, cross-sectional studies, often from patient samples, consistently show associations between white matter lesions (WMLs) and depression (Greenwald et al, 1998;Ikram et al, 2010;Kumar et al, 2000;Kumar et al, 2002). The results from longitudinal population-based studies are conflicting.…”

“…It has been suggested that cortical atrophy and WMLs represent two relatively independent pathways to major depression in the elderly (Kumar et al, 2000;Kumar et al, 2002). This hypothesis was based on a cross-sectional clinical study, and has not been tested in longitudinal population-based studies.…”

Mood, cognition and in vivo protein imaging: the emerging nexus in clinical neuroscience

“…It is important to remember that while AD is not typically conceptualized as a vascular dementia, mixed vascular-degenerative dementias are increasingly recognized both clinically and neuropathologically. Vascular mechanisms clearly contribute to late-life depression and preliminary work in our laboratory indicates that smaller frontal lobe volumes (degeneration) and high intensity lesions (putatively linked to vascular disease) detected using MRI are complementary, albeit autonomous pathways to MDD (Kumar et al, 2000(Kumar et al, , 2002a. These pathways are comparable to mechanisms and pathways that have been implicated in AD and mixed dementia and suggest that neurodegeneration and vascular compromise may represent pathophysiological mechanisms that transcend traditional diagnostic boundaries.…”