Research Shows Depression May Reduce Brain Memory Centre Volume in Older Adults

What if depression quietly shrinks your brain's memory center-long before memory problems even begin?

Depression may leave a subtle mark on the aging brain years before dementia symptoms appear, according to a new study from the USC Mark and Mary Stevens Neuroimaging and Informatics Institute. Researchers found that older adults with depression had a smaller volume in a specific part of the hippocampus—a brain region essential for learning and memory—even though they had no signs of cognitive impairment.

Published in Translational Psychiatry, the study analyzed high-resolution brain scans from 2,009 cognitively healthy adults aged 50 to 90 years. Of these, 630 participants had depression based on current symptoms or a previous diagnosis.

Instead of examining the hippocampus as a single structure, researchers focused on three subregions. They found that depression was specifically linked to a smaller CA23DG region, which plays a crucial role in retrieving memories, distinguishing between similar experiences, and reconstructing memories from incomplete information. No significant differences were seen in the CA1 or subiculum regions.

Importantly, the association remained even after accounting for body mass index, physical activity, amyloid and tau proteins, and the APOE ε4 gene—well-known Alzheimer's disease risk factors. This suggests depression may affect brain structure through biological pathways that are at least partly separate from those linked to Alzheimer's disease.

The researchers also observed that participants with depression who reported taking antidepressants had smaller CA1 and CA23DG volumes than those not taking medication. However, they stressed this does not mean antidepressants caused the changes. People receiving medication may have experienced more severe or long-lasting depression, and the study could not separate medication effects from illness severity.

The findings do not prove that depression causes brain shrinkage or predicts Alzheimer's disease. Instead, they highlight a vulnerable memory-related brain region and reinforce the importance of recognizing and treating depression as part of healthy brain aging.

REFERENCE: Luu, D., Twisselmann, A.M., Tennant, V.R. et al. Depression and hippocampal subfield volume in older adults. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-04223-y