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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.
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