Abstract
Increasing evidence has accumulated for structural brain changes associated with unipolar
recurrent major depression. Studies of neuroanatomic structure in early-onset recurrent
depression have only recently found evidence for depression-associated structural
change. Studies using high-resolution three-dimensional magnetic resonance imaging
(MRI) are now available to examine smaller brain structures with precision. Brain
changes associated with early-onset major depression have been reported in the hippocampus,
amygdala, caudate nucleus, putamen, and frontal cortex, structures that are extensively
interconnected. They comprise a neuroanatomic circuit that has been termed the limbic–cortical–striatal–pallidal–thalamic
tract. Of these structures, volume loss in the hippocampus is the only consistently
observed change to persist past the resolution of the depression. Possible mechanisms
for tissue loss include neuronal loss through exposure to repeated episodes of hypercortisolemia;
glial cell loss, resulting in increased vulnerability to glutamate neurotoxicity;
stress-induced reduction in neurotrophic factors; and stress-induced reduction in
neurogenesis. Many depressed patients, particularly those with late-onset depression,
have comorbid physical illnesses producing a high rate of hyperintensities in deep
white matter and subcortical gray matter and brain damage to key structures involved
in the modulation of emotion. Combining MRI studies with functional studies has the
potential to localize abnormalities in blood flow, metabolism, and neurotransmitter
receptors and provide a better integrated model of depression.
Keywords
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Article info
Publication history
Accepted:
July 19,
2000
Received in revised form:
July 10,
2000
Received:
March 28,
2000
Identification
Copyright
© 2000 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
