Patients with recurrent depression have smaller hippocampi

The brains of people with recurrent depression have a significantly smaller hippocampus than healthy individuals, according to a global study of nearly 9,000 people. This appears to be particularly true for adolescent patients with early onset depression. This study highlights the need to identify and treat depression effectively when it first occurs, particularly among teenagers and young adults.

Major depression is a very common condition that affects at least 1 in 6 people (>16%) during their lifetime. It is a serious clinical mood disorder and is among the leading causes of disability worldwide.

Prior research has found structural alterations in various subcortical brain regions in people with major depressive disorder (MDD). But volumetric differences have not been consistent and sample sizes were often small.

To overcome some of those issues, researchers from around the world initiated the MDD Working Group within the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium—an international collaboration currently evaluating 15 research samples from 6 different countries worldwide. The research, published in Molecular Psychiatry, is the largest international study to compare brain volumes in people with and without major depression.

Using magnetic resonance imaged (MRI) brain scans and clinical data from 1,728 people with major depression and 7,199 healthy individuals, ENIGMA researchers found robust reductions in hippocampal volume (1.24%) in MDD patients compared with healthy controls. This key finding was largely explained by subjects with recurrent depression, a group that represented 65% of MDD subjects in the study.

People with an early age of onset of major depression (before age 21) also had a smaller hippocampus than healthy individuals, consistent with the notion that many of these young people go on to have recurrent disorders.

However, people who had a first episode of major depression (34% of MDD subjects) did not have a smaller hippocampus than healthy individuals, indicating that the changes are due to the adverse effects of depressive illness on the brain.

"This new finding of smaller hippocampal volume in people with major depression may offer some support to the ‘neurotrophic hypothesis of depression,’" said one of the study’s co-authors, Jim Lagopoulos, PhD, Associate Professor of the University of Sydney's Brain and Mind Research Institute (BMRI) in Camperdown, Australia. "This hypothesis argues that a range of neurobiological processes, such as elevated glucocorticoid levels in those with chronic depression, may induce brain shrinkage.”

In that regard, abnormal hippocampal development may predate the onset of adolescent depression, and may represent risk markers for depression, recurrence and chronicity, the study authors concluded.

"This large study confirms the need to treat first episodes of depression effectively, particularly in teenagers and young adults, to prevent the brain changes that accompany recurrent depression,” said Ian Hickie, MD, Professor and Co-Director of BMRI.

This study’s findings suggest that the hippocampus is a prime target region for future research aimed at further unraveling the pathophysiology of MDD and improving treatment, the authors concluded.

Dr. Hickie added, "Clearly, there's a need for longitudinal studies that can track changes in hippocampal volume among people with depression over time to better clarify whether hippocampal abnormalities result from prolonged duration of chronic stress, or represent a vulnerability factor for depression, or both.”

For more information on depression, visit the Depression Resource Center on MDLinx.