Background Information

Major Depression is one of the most frequent psychiatric syndromes in late life and a major source of excess suffering and disability. The causes of Major Depression, however, remain largely unknown.  As has been true for disorders such as Alzheimer Disease, Parkinson Disease, and Schizophrenia, advances in our understanding of the mechanisms underlying Major Depression may benefit from the study of brain tissue. Traditionally, brain tissue studies of Major Depression have relied on measures of neurotransmitter receptors in frozen tissue specimens. More recently, guided in part by brain imaging studies of living patients with Major Depression, investigators have used techniques to identify subtle regional changes in cell structure and density


These early findings of the changes in brain tissue from patients with Major Depression have often been limited by the nature and quality of the brain tissue samples.  These studies have frequently utilized brain tissue from subjects who had not been evaluated by a psychiatrist while alive, having to rely instead on determination of the diagnosis of Major Depression after death, a procedure potentially less reliable than diagnoses assigned during life. Nor have studies addressed issues specifically relevant to Late Life Major Depression. For example, Late Life Major Depression is frequently associated with cognitive impairment, and many patients subsequently develop dementia.  Both cerebrovascular disease and Alzheimer Disease have been hypothesized to cause this deterioration, though studies have yet to test these hypotheses definitively by examining brain tissue.  Because Alzheimer Disease is also known to affect brain tissue concentrations of neurotransmitters and their receptors, the extent of Alzheimer Disease changes needs to be assessed and controlled when studying neurotransmitters in individuals with Late Life Major Depression. 


To address these issues, we have established a brain tissue collection from a cohort of Late Life Major Depression patients modeled on the approach used successfully in Alzheimer Disease Research Centers. Individual participants agree while alive to the donation of brain tissue after death. Participants are carefully characterized while alive with regard to psychiatric diagnosis, cognitive functioning, other medical illness, treatment history, and illness course. This prospective, longitudinal methodology provides a wealth of accurate, reliable clinical data that can then be correlated with results of quantitative studies of the brain tissue.  To our knowledge, this is the first attempt to establish such a resource.


Preliminary findings from this project were recently reported (Sweet et al, 2004).  Seven out of the first ten (70%) participants with mood disorders had evidence of dementia onset prior to death.  After reviewing the neuropathologic diagnoses of those seven, six (86%) had Alzheimer Disease pathology, four (57%) had Dementia with Lewy Bodies, and four (57%) with had Cerebrovascular pathology.  Neither Dementia with Lewy Bodies or Cerebrovascular pathology were found more frequently in patients with dementia than without dementia, but an association between Alzheimer Disease pathology and dementia was found to be statistically significant, even with such a small sample.  Although they were preliminary, these findings suggest that the increased risk for subsequent dementia in individuals with Late Life Major Depression is due to a specific increased risk for Alzheimer Disease as the predominant neuropathologic condition.




Current Studies

Late Life Mood Disorders Brain Tissue Collection

The Aims of this project are:

1) To establish a Late Life Mood Disorder (LLMD)  Brain Tissue Collection for elderly subjects with LLMD, prospectively and extensively characterized as part of ongoing participation in clinical and neuroimaging research trials conducted through the LLMD Intervention Research Center, to serve as a local and national resource for brain tissue study, and an exemplar for future efforts at other centers.

2) To identify the neuropathologic correlates of LLMD we will conduct standard research neuropathologic examinations, establishing neuropathologic diagnoses of Alzheimer Disease, Dementia with Lewy Bodies, and Vascular Dementia, and quantifying the pathologic features in all cases.


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Last Updated:

August 30, 2011