Background
Structural brain changes have often been found in major depressive disorder (MDD),
and it is thought that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity may
explain this relation. We investigated the association of MDD and history of depression
with hippocampal and entorhinal cortex volumes and whether HPA axis activity explained
this association.
Methods
In 636 participants with a history of atherosclerotic disease (mean age 62 ± 9 years,
81% male) from the second Manifestation of ARTerial disease-Memory depression and
aging (SMART-Medea) study, a 12-month diagnosis of MDD and history of depression were
assessed. Age of first depressive episode was classified into early-onset depression
(< 50 years) and late-onset depression (≥ 50 years). HPA axis regulation was assessed
by four morning saliva samples, two evening samples, and one awakening sample after
.5 mg dexamethasone. Hippocampus and entorhinal cortex volume were manually outlined
on three-dimensional T1-weighted magnetic resonance images.
Results
General linear models adjusted for demographics, vascular risk, antidepressant use,
and white matter lesions showed that ever having had MDD was associated with smaller
hippocampal volumes but not with entorhinal cortex volumes. Remitted MDD was related
to smaller entorhinal cortex volumes (p < .05). Participants with early-onset depression had smaller hippocampal volumes
than those who were never depressed (p < .05), whereas participants with late-onset depression had smaller entorhinal cortex
volumes (p < .05). HPA axis activity did not explain these differences.
Conclusions
We found differential associations of age of onset of depression on hippocampal and
entorhinal cortex volumes, which could not be explained by alterations in HPA axis
regulation.
Key Words
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Article info
Publication history
Published online: March 25, 2011
Accepted:
January 27,
2011
Received in revised form:
January 18,
2011
Received:
September 28,
2010
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Depression and the Hippocampus: Cause or Effect?Biological PsychiatryVol. 70Issue 4
- PreviewResearch examining the relationship between major depressive disorder (MDD) and hippocampal volume has long wrestled with the chicken and egg question. From the time the first report was published finding smaller hippocampal volumes in patients with MDD compared with healthy control subjects (1), there have been hundreds of studies in the literature, with the majority, but not all, finding smaller hippocampal volumes in MDD (2). The direction of a potential causal arrow, however, remains unresolved.
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