Examining Hippocampal Volume In Older Adults With Depression

The overall prevalence of depression among the older population is around 7% and, hence, is a major health issue. Depression may be associated with global cerebral gray matter change. In particular, several structural magnetic resonance imaging (MRI) studies examined the neuro-structural correlates of depression, highlighting volume reductions in a specific brain structure called the hippocampus (HC) in patients with depression, including older adults, in comparison with healthy controls.

In our study, we investigated the volume differences in the HC in a general population sample of French older adults (the “Enquête de Santé Psychologique – Risques, Incidence et Traitement” or ESPRIT study). We compared 3 groups: 1) currently depressed individuals, 2) persons with a past major depressive episode (MDE), and 3) healthy controls.

In this project, subjects aged 65 and over were randomly recruited from the 15 electoral rolls of the Montpellier district (South of France) between March 1999 and February 2001. Participants underwent clinical, biological, and neuroimaging assessment at the Gui de Chauliac Neurology Hospital of Montpellier.

We used T1-weighted magnetic resonance images and both a) FreeSurfer Software (automated method) and b) a manual method to measure HC, dividing it into head, body, and tail.

1. We were able to find a left posterior HC volume reduction in currently depressed participants compared to healthy controls with the manual HC measurement. When individuals with a history of past, but not current, MDE were compared to those who never experienced depression, no HC volume reduction was found.

1. Moreover, when we slightly changed sub-group inclusion criteria (i. including only subjects with a more strict diagnosis of depression; ii. excluding subjects taking antidepressants; and iii. adding metabolic syndrome among confounding factors) the main result remained. In fact, brain volume changes due to depression in older adults may be modified by a number of confounding factors, such as depression severity, antidepressant use, or cardiovascular risk linked to the metabolic syndrome.

What are the plausible implications of our main results?

Our results are fairly in line with former studies supporting HC volume reduction in depression among older adults. Though, in our study, only the left posterior HC volume revealed a significant reduction. This is probably due to the strict methodological adjustments we made to avoid type I errors (i.e. what is called a “false positive” finding, meaning a result found by chance).

A recent MRI study reported the same result in individuals suffering from late-onset depression versus controls. This could mean that measuring total HC volume without considering its sub-fields is less relevant in the analysis of HC volume changes in depression.

Notably, only with the manual method, with its greater accuracy compared to automated methods, we were able to detect differences in HC volumes. This could mean that the actual accuracy of automated methods did not yet match that of the manual one.

How we can explain the presence of reduced HC volume in current depressed individuals but not in one with a past depressive episode?

The hypothesis is that past depressed individuals may have recovered in terms of brain atrophy.

In fact, neural circuits and connections undergo permanent modifications and reorganization in reaction to external or internal environmental stimuli: this is known as the Neuroplasticity theory. Indeed, it appears that neurogenesis in adulthood involves precursors of cell proliferation, migration and differentiation largely occurring in the dentate gyrus of the HC, therefore producing new neurons throughout life. On one hand, stress-induced reduction in neurogenesis may be a significant factor in precipitating episodes of depression. On the other, the recovery from depression could involve a restoration of the original basal rate of neurogenesis (whether it is due to antidepressant treatment or endogenous changes).

In the future, it would be interesting to develop longitudinal imaging studies following participants during several years to better measure brain changes in depressed older adults.

These findings are described in the article entitled Smaller hippocampal volume in current but not in past depression in comparison to healthy controls: Minor evidence from an older adults sample, recently published in the Journal of Psychiatric Research. This work was conducted by Ismaïl Bensassi and Jorge Lopez-Castroman from the University of Montpellier and CHRU Nimes, Jerome J. Maller from the Alfred & Monash University Central Clinical School and General Electric Healthcare, Chantal Meslin from the Australian National University, Marilyn Wyart from CHRU Nimes, Karen Ritchie from the University of Montpellier and the University of Edinburgh, Philippe Courtet from the University of Montpellier, CHU Montpellier, and FondaMental Foundation, Sylvaine Artero from the University of Montpellier, and Raffaella Calati from the University of Montpellier and FondaMental Foundation.