University of Southern California study links depression to hippocampal shrinkage

Researchers at the University of Southern California have identified a specific reduction in brain volume linked to major depressive disorder. A study published in the journal Translational Psychiatry, involving over 2,000 cognitively unimpaired adults aged 50 to 90, found that individuals with depression exhibit a smaller volume in a specific subregion of the hippocampus known as CA23DG.

The CA23DG region, which includes the CA2 and CA3 subfields and the dentate gyrus, is critical for memory consolidation, learning, and pattern separation. The study indicates that this structural change appears to operate independently of common Alzheimer’s disease risk factors, such as amyloid and tau protein levels or the APOE ε4 genetic variant.

Lead author Danielle Luu noted that while depression has long been associated with an increased risk of Alzheimer’s, the precise biological connection has remained unclear. The findings suggest that the duration of depression may be a primary driver of these structural changes. However, experts emphasize that due to neural plasticity, these alterations are not necessarily permanent and may be supported by treatments such as therapy and exercise.