Question

How does the glucocorticoid hypothesis of depression explain changes that occur in the hippocampus in individuals experiencing depression, and what are the changes seen in the hippocampus?

Answer 1

While depression can affect a person psychologically, it also has the potential to affect physical structures in the brain. The following parts of the brain can be affected:

• hippocampus
• thalamus
• amygdala
• frontal
• prefrontal cortices

The hippocampus is one region that has recently received significant attention in mood disorders research and, although almost certainly not solely responsible for the myriad of symptoms observed in depression, the highly plastic, stress-sensitive hippocampal region may play a central role in depressive illness.

Results provide some evidence for relationships between depression and decrease in right hippocampal volume. This would be consistent with depression as a causal factor in subsequent cognitive decline. Plausible biological mechanisms include a glucocorticoid cascade or a facilitating effect of depression on amyloid-beta plaque formation. Future studies should examine the relationship between hippocampal volume and specialized memory measures, as well as between depression diagnosis and volume of other brain structures.

Converging lines of research suggest that the hippocampal complex (HC) may have a role in the pathophysiology of major depressive disorder (MDD). Although postmortem studies show little cellular death in the hippocampal complex (HC) of depressed patients, animal studies suggest that elevated glucocorticoid levels associated with major depressive disorder (MDD) may negatively affect neurogenesis, cause excitotoxic damage or be associated with reduced levels of key neurotrophins in the hippocampal complex (HC) . Antidepressant medications may counter these effects, having been shown to increase hippocampal complex (HC)   neurogenesis and levels of brain-derived neurotrophic factor in animal studies. Neuropsychological studies have identified deficits in hippocampus-dependent recollection memory that may not abate with euthymia, and such memory impairment has been the most reliably documented cognitive abnormality in patients with major depressive disorder (MDD). Finally, data from imaging studies suggest both structural changes in the volume of the hippocampal complex (HC)   and functional alterations in frontotemporal and limbic circuits that may be critical for mood regulation. The extent to which such functional and structural changes determine clinical outcome in major depressive disorder (MDD) remains unknown; a related, but also currently unanswered, question is whether the changes in hippocampal complex (HC)   function and structure observed in major depressive disorder (MDD) are preventable or modifiable with effective treatment for the depressive illness.