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bioRxiv · 10.64898/2026.09.09.750514

An updated roadmap for brain-mental health associations in the UK Biobank

Li, X.·Khalife, S.·Oestreich, L. K. L.
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Abstract

The UK Biobank offers an unprecedented opportunity to examine associations between brain imaging and mental health at scale, but their magnitude and replicability remain unclear. We correlated 17,580 imaging-derived phenotypes across seven MRI modalities with 309 mental health phenotypes in 8,415 participants, split into discovery and validation subsets. Associations were generally small (median |r| = 0.018; top 1% of 0.108), and they replicated poorly: only 9.0% of significant discovery associations were significant in validation. Eating disorders showed the largest effects of any mental disorders but replicated in only 6.0% of cases, whereas substance use showed the highest replication (14.5%). Susceptibility-weighted imaging produced the most replicable imaging associations. Longitudinal changes in brain and mental health measures were weakly related. We provide an interactive dashboard that returns the effect-size and replicability benchmarks for any combination of mental health category and imaging modality, supporting variable selection and study design in UK Biobank research.

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Li, X., Khalife, S., Oestreich, L. K. L.. 2026-09-13. An updated roadmap for brain-mental health associations in the UK Biobank. https://doi.org/10.64898/2026.09.09.750514

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