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Despite several decades of neuroimaging studies reporting brain structural and functional alterations in depression, discrepancies in findings across various studies and limited convergence across several recent meta-analyses have raised questions about the consistency and robustness of the observed brain phenotypes.

To investigate the effects of six different operational criteria of lifetime exposure to depression on functional and structural neuroimaging measures.

A cross-sectional study analyzed data from the UK biobank in individuals aged 45 to 80 years enrolled from 2014 to 2018. Six operational depression criteria were defined: Help-seeking for depression, Self-reported Depression, Antidepressant usage, Depression defined by Smith, Hospital International Classification of Disease, 10th Edition (ICD-10), and short-form Composite International Diagnostic Interview. Six increasingly conservative groups of lifetime depression were defined based on the six available depression criteria from meeting only one to more restrictive meeting all six criteria. We tested the effect of these definitions on voxel-wise measures of local functional activity, global connectivity, and gray matter volume.

Voxel-wise fractional amplitude of low-frequency fluctuations, local connectivity, global connectivity, and gray matter volume.

We included 20,484 individuals with lifetime depression (12,645 women [61.73%]; mean [SD] age, 63.92 [7.6] years) and 25,462 healthy individuals (11,384 women [44.7%]; mean [SD] age, 65.05 [7.8] years) from the UK biobank. Across all depression …