Aug 18, 2026 19:00:00

Research shows that areas of the brain associated with memory and learning are reduced in patients with depression.

While depression has long been known as a risk factor for Alzheimer's disease, the interaction between depression and cognitive decline is not well understood. A new study of middle-aged and older adults with depression has revealed that the volume of specific areas of

the hippocampus , which are involved in memory and learning, is reduced in the brains of depressed patients.

Depression and hippocampal subfield volume in older adults | Translational Psychiatry
https://www.nature.com/articles/s41398-026-04223-y

Depression linked to smaller volume in key memory region of older adults
https://keck.usc.edu/news/depression-linked-to-smaller-volume-in-key-memory-region-of-older-adults/

A Specific Part of Your Brain Seems to Shrink If You Have Depression : ScienceAlert
https://www.sciencealert.com/a-crucial-part-of-the-brains-memory-center-seems-to-shrink-in-people-with-depression

The hippocampus is a brain region that plays a crucial role in memory formation and retrieval, and it is composed of multiple subregions, each with different functions. These subregions may show different responses to aging, depression, and neurodegenerative diseases, and focusing only on the hippocampus as a whole may lead to overlooking the connection to these diseases.

In this study, a research team at the University of Southern California used high-resolution MRI scans to measure three regions that make up the hippocampus: CA1 , the hippocampal subcolumnar , and CA23DG (a complex region including CA2, CA3 , and the dentate gyrus ). Of these, CA1 is a region that helps the brain recognize new information and link it to known information, the hippocampal subcolumnar is a major pathway for transmitting information to other parts of the brain, and CA23DG is an important region for memory retrieval and reconstruction.

Daniel Lu, lead author of the paper and a doctoral student in the University of Southern California's School of Neuroscience, said, 'Depression has long been associated with an increased risk of developing Alzheimer's disease, but the biological link between the two is still not fully understood. By examining individual regions of the hippocampus in detail, we identified areas that may be particularly sensitive to depression in older adults.'

The study involved MRI scans of 2,009 participants aged 50-90 with normal cognitive function. Of these participants, 630 were classified as having depression based on their current symptoms and past diagnoses, while the remaining 1,379 were not. Because all participants had normal cognitive function, the research team was able to measure brain changes that occur before memory loss or cognitive decline appears.

When analyzed after taking into account factors such as age, sex, body mass index (BMI), and physical activity level, it was revealed that patients with depression had a smaller volume of CA23DG compared to subjects without depression. On the other hand, no decrease in CA1 or hippocampal lobe was observed in patients with depression.

This trend remained largely unchanged even when considering factors such as

amyloid precursor protein , tau protein , and APOE gene mutations, which are risk factors for Alzheimer's disease. This suggests that known Alzheimer's disease risk factors are not involved in the decrease of CA23DG, and that depression and CA23DG are associated through their own unique pathways.

However, when the research team took antidepressant use into consideration, they found that subjects taking antidepressants had smaller volumes not only of CA23DG but also CA1. This result seems counterintuitive, as antidepressants are generally thought to mitigate the harmful physiological effects of depression. The research team speculates that people with more severe symptoms of depression are more likely to be prescribed antidepressants, and as a result, the impact on the hippocampus may have been greater.

Similarly, the research team found that people who had suffered from depression for a long period, even if their symptoms were mild and under control, were more strongly associated with a decrease in CA23DG volume compared to people who had severe symptoms of depression but had only recently started suffering from it. This trend suggests that not only the severity but also the duration of depression influences changes in the hippocampus.

Further research is needed to understand the mechanisms by which depression causes these changes in the hippocampus of patients. This study only shows a correlation and does not prove a causal relationship that 'depression or antidepressants cause a decrease in CA23DG volume.'

Dr. Lu cautioned, 'This study cannot separate the potential effects of the medication from the effects caused by the depression itself, which is more severe than the condition for which the medication is prescribed. To understand these relationships, long-term studies that track patients before and after treatment are essential. These results should not be interpreted as a reason to change or discontinue prescription medications.'