High-resolution scans reveal how depression affects hippocampal subfields

Researchers from the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC have found that depression is associated with smaller volume in a specific part of the hippocampus, a brain region essential for learning and memory.

The study, published in Translational Psychiatry, examined high-resolution brain scans from 2,009 cognitively healthy adults ages 50 to 90. Researchers found that participants with depression had smaller volumes in a hippocampal area encompassing the CA2, CA3, and dentate gyrus, collectively called the CA23DG. The association remained after researchers accounted for body mass index, physical activity, and several major biological indicators of Alzheimer's disease risk, including amyloid and tau proteins and the APOE ε4 genetic variant.

Depression has long been associated with an increased risk of developing Alzheimer's disease, but we still do not fully understand the biological connection between the two. By looking closely at the individual parts of the hippocampus, we identified a specific area that may be particularly sensitive to depression in older adults."

The hippocampus plays a central role in forming and retrieving memories. Although it is often discussed as a single brain region, it is made up of several smaller sections, or subfields, that perform different functions and may respond differently to aging, depression, and neurological disease. Studying the hippocampus as a whole can obscure changes concentrated in only one of these subfields. For the new study, researchers used high-resolution MRI scans to measure three areas: CA1; the subiculum; and CA23DG, a combined region containing CA2, CA3, and the dentate gyrus. Each of these areas contributes to learning and memory in a different way. CA1 helps the brain recognize new information and connect it with what is already known. CA23DG plays a particularly important role in retrieving memories, distinguishing between similar experiences, and using partial information to reconstruct more complete memories. The subiculum serves as a major pathway for carrying information from the hippocampus to other parts of the brain.