Depression in older adults is associated with a smaller volume in one specific corner of the hippocampus, according to researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC. Writing in Translational Psychiatry, the team analyzed high-resolution brain scans from 2,009 cognitively healthy adults between the ages of 50 and 90 and found that those with depression had less volume in a region combining the CA2, CA3, and dentate gyrus areas, referred to collectively as CA23DG.
What makes the finding notable is what it survived. The association held after the researchers adjusted for body mass index, physical activity, and several of the biological markers most closely tied to Alzheimer's risk, including amyloid and tau proteins and the APOE e4 gene variant. In other words, the smaller CA23DG volume was not simply a reflection of underlying Alzheimer's pathology or lifestyle differences among participants.
The hippocampus is usually talked about as a single structure, but it is built from subfields with distinct jobs, and lumping them together can hide changes confined to just one. The study measured three: CA1, which helps the brain recognize new information and link it to existing knowledge; the subiculum, the main route carrying signals out of the hippocampus; and CA23DG, which is heavily involved in retrieving memories, telling similar experiences apart, and reconstructing a full memory from fragments. Only CA23DG showed the depression-related difference.
Depression has long been tied to a higher risk of later developing Alzheimer's disease, yet the biology linking the two has remained murky. As the study's authors put it, examining the individual parts of the hippocampus allowed them to pinpoint an area that may be particularly sensitive to depression in older adults. Because the participants were cognitively healthy, the work identifies an association rather than a chain of cause and effect, but it gives future research a much narrower target than the hippocampus as a whole.