Depression doesn’t shrink the brain like we thought it did
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- Janine Bijsterbosch and colleagues at Washington University School of Medicine in St Louis analyzed 23,417 brain scans across six large-scale US and UK datasets, including the UK Biobank, and found no significant link between depression and hippocampal volume.
- The finding directly challenges a 2015 study of nearly 9,000 people that concluded people with recurrent depression have smaller hippocampi that shrink further with each episode — a conclusion Bijsterbosch's team attributes partly to modern imaging techniques unavailable in 2015.
- John Fleming of the Southern Colorado TMS Center called the null result "surprising," adding that the study tells researchers "not to take hippocampal shrinkage as a given" and that more needs to be learned about other brain regions.
- The team did detect depression-linked reductions in grey matter volume or cortical surface area in the frontal cortex, anterior cingulate, and insula — all regions involved in emotional regulation that could help explain symptoms like brain fog and pain, Fleming said.
- Bijsterbosch noted key caveats: depression was measured at only a single time point, and most participants had mild to moderate symptoms, leaving open the possibility that hippocampal shrinkage does occur in recurrent or severe depression.
- Fleming suggested the research could inform the depression-dementia link, noting that a larger brain may delay cognitive decline past a damage threshold — though he stressed dementia involves many factors including inflammation and protein plaques.
- Bijsterbosch said transcranial magnetic stimulation, which has been linked to modest brain volume increases, could be explored as a treatment if future research robustly ties brain shrinkage to depression.
- The study was published in Nature Mental Health (DOI: 10.1038/s44220-026-00680-y).
Why it matters: For more than a decade, the hippocampus-shrinkage model shaped both clinical assumptions about depression's neurological toll and the rationale for hippocampus-targeted therapies. This 23,000-scan null result — while not dismissing shrinkage in severe or recurrent cases — redirects researchers toward the frontal cortex, anterior cingulate, and insula, potentially reshaping where future treatments like TMS are aimed and how the depression-dementia connection is investigated.
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