Abstract
A number of studies indicate that prolonged, major depression is associated with a
selective loss of hippocampal volume that persists long after the depression has resolved.
This review is prompted by two ideas. The first is that overt neuron loss may be a
contributing factor to the decrease in hippocampal volume. As such, the first half
of this article reviews current knowledge about how hippocampal neurons die during
insults, focusing on issues related to the trafficking of glutamate and calcium, glutamate
receptor subtypes, oxygen radical generation, programmed cell death, and neuronal
defenses. This is meant to orient the reader toward the biology that is likely to
underlie any such instances of neuron loss in major depression. The second idea is
that glucocorticoids, the adrenal steroids secreted during stress, may play a contributing
role to any such neuron loss. The subtypes of depression associated with the hippocampal
atrophy typically involve significant hypersecretion of glucocorticoids, and the steroid
has a variety of adverse effects in the hippocampus, including causing overt neuron
loss. The second half of this article reviews the steps in this cascade of hippocampal
neuron death that are regulated by glucocorticoids.
Keywords
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Article info
Publication history
Accepted:
July 3,
2000
Received in revised form:
June 26,
2000
Received:
March 9,
2000
Identification
Copyright
© 2000 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
