Depression may be connected with subtle differences in a part of the brain that helps people form and retrieve memories, according to a large study of older adults.
Researchers found that people with depression had a smaller volume in one specific section of the hippocampus, even though they showed no signs of cognitive impairment.
The hippocampus is a small structure deep inside the brain that plays an essential role in learning and memory. It is also one of the brain regions closely studied in aging because changes there can occur in conditions such as Alzheimer’s disease.
Scientists from the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC wanted to examine the hippocampus in greater detail. Instead of treating it as one structure, they studied several smaller sections that have different jobs.
The researchers analyzed high-resolution MRI brain scans from 2,009 adults between ages 50 and 90. All participants were considered cognitively healthy, meaning they did not have the memory or thinking problems used to diagnose cognitive impairment.
Of the participants, 630 were classified as having depression based on current symptoms or a previous diagnosis reported from a healthcare provider. The other 1,379 participants were not classified as having depression.
The team focused on three parts of the hippocampus. These included CA1, the subiculum and a combined area called CA23DG, which contains CA2, CA3 and the dentate gyrus.
These names describe small areas with different roles in memory. CA1 helps the brain work with new information, while the subiculum is an important route through which information leaves the hippocampus and travels to other brain regions.
CA23DG is particularly interesting because it helps people distinguish between similar experiences and retrieve memories. It can also help the brain rebuild a more complete memory when only part of the original information is available.
When researchers compared the scans, depression was associated with a smaller CA23DG volume. They did not find a significant depression-related difference in CA1 or the subiculum.
This suggests that depression may not be associated with a general reduction across the entire hippocampus. Instead, the relationship may be concentrated in particular memory-related areas.
The researchers also wanted to know whether the finding could simply reflect well-known biological risks for Alzheimer’s disease. Depression has previously been associated with a higher risk of developing dementia, but scientists still do not fully understand why.
To explore this question, the team examined amyloid and tau, two proteins that can build up abnormally in the brains of people with Alzheimer’s disease. They also looked at APOE ε4, a genetic variant known to increase Alzheimer’s risk.
Even after these factors were considered, the relationship between depression and smaller CA23DG volume remained. The researchers also accounted for factors including body mass index and physical activity.
This does not mean that depression causes Alzheimer’s disease or that people with a smaller CA23DG will eventually develop dementia. Instead, the results suggest that depression may be related to brain structure through biological pathways that are at least partly separate from amyloid, tau and APOE ε4.
The researchers also examined antidepressant use. Among participants with depression, those who reported taking antidepressants had smaller CA1 and CA23DG volumes than those who were not taking the medicines.
However, the researchers strongly cautioned against concluding that antidepressants caused these differences. People who take antidepressants may have had more severe or longer-lasting depression, and the study did not contain enough information about treatment duration, dosage or past symptom severity to separate these possibilities.
The findings therefore should not be used as a reason to stop or change prescribed antidepressant treatment. Long-term research following people before and after treatment would be needed to determine whether medication itself has any relationship with changes in hippocampal volume.
The study used data from the Health and Aging Brain Study–Health Disparities, known as HABS-HD. The project includes Hispanic, non-Hispanic Black and non-Hispanic white adults, giving researchers an opportunity to study healthy brain aging in a more diverse population.
The research was published in Translational Psychiatry. The study was led by Danielle Luu, with Meredith N. Braskie as senior author, and involved researchers at the Keck School of Medicine of USC.
A major strength of the study is its large sample and detailed brain imaging. Looking at individual hippocampal areas can reveal differences that might disappear when researchers measure only the total size of the hippocampus.
Still, the study provides a snapshot rather than showing what happened to each person’s brain over time. It therefore cannot determine whether depression led to smaller CA23DG volume, whether pre-existing brain differences increased vulnerability to depression, or whether another factor influenced both.
Depression is also a complex condition with many possible causes and patterns. Future studies that track symptoms, treatment and brain changes for years could provide a clearer picture of how mental health and memory systems interact during aging.
Overall, the study adds an important piece to the puzzle linking depression, aging and brain health. It suggests that researchers may gain more insight by examining specific memory circuits rather than viewing the hippocampus as a single structure, while also making clear that the findings do not show that depression inevitably leads to dementia.
If you care about health, please read studies about how dairy foods may influence depression risk, and B vitamins could help prevent depression and anxiety.
For more health information, please see recent studies that ultra-processed foods may make you feel depressed, and extra-virgin olive oil could reduce depression symptoms.
Source: University of Southern California.
