The neuroimaging correlates of depression established across six large-scale datasets

Hamilton, K. M.; Luo, X. D.; Easley, T. O.; Ahmad, F.; Guo, T.; Jarukasemkit, S.; Modi, H.; Rincon, S. N.; Shelton, C.; Stahl, L.; Wang, Z.; Zhu, Y.; Lenzini, P.; Hannon, K.; Bijsterbosch, J. D.

doi:10.1101/2025.07.02.660888

bioRxiv · 10.1101/2025.07.02.660888

The neuroimaging correlates of depression established across six large-scale datasets

Hamilton, K. M.·Luo, X. D.·Easley, T. O.·Ahmad, F.·Guo, T.·Jarukasemkit, S.·Modi, H.·Rincon, S. N.·Shelton, C.·Stahl, L.·Wang, Z.·Zhu, Y.·Lenzini, P.·Hannon, K.·Bijsterbosch, J. D.

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Abstract

Neuroimaging data offers noninvasive insights into the structural and functional organization of the brain and is therefore commonly used to study the neuroimaging correlates of depression. To date, a substantial body of literature has suggested reduced size of subcortical regions and abnormal functional connectivity in frontal and default mode networks linked to depression. However, recent meta analyses have failed to identify significant converging correlates of depression across the literature such that a conclusive mapping of the neuroimaging correlates of depression remains elusive. Here we leveraged 23,417 participants across six datasets to comprehensively establish the neuroimaging correlates of depression. We found reductions in gray matter volume/ cortical surface area associated with depression in the frontal cortex, anterior cingulate, and insula, confirming prior studies showing the importance of prefrontal and default mode regions in depression. Our findings demonstrate multiple surprising results, including a lack of depression correlates in subcortical brain regions, significant depression correlates in somatomotor and visual regions, and limited functional connectivity findings. Overall, these results shed new light on key brain regions involved in the pathophysiology of depression, updating our understanding of the neuroimaging correlates of depression. We anticipate that these insights will inform further research into the role of sensorimotor and visual regions in depression and into the impact of heterogeneity on functional connectivity correlates of depression.

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Hamilton, K. M., Luo, X. D., Easley, T. O., Ahmad, F., Guo, T., Jarukasemkit, S., Modi, H., Rincon, S. N., Shelton, C., Stahl, L., Wang, Z., Zhu, Y., Lenzini, P., Hannon, K., Bijsterbosch, J. D.. 2025-07-08. The neuroimaging correlates of depression established across six large-scale datasets. https://doi.org/10.1101/2025.07.02.660888

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