Effect of lifetime exposure to depression on brain structure and function in the UK Biobank

ImportanceDespite 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. ObjectiveTo investigate the effects of six different operational criteria of lifetime exposure to depression on functional and structural neuroimaging measures. Design, Setting, ParticipantsA 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. Main Outcomes and MeasuresVoxel-wise fractional amplitude of low-frequency fluctuations, local connectivity, global connectivity, and gray matter volume. ResultsWe 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 definitions, individuals with lifetime depression displayed regionally consistent decreases in local functional activity in sensorimotor regions but not in global connectivity and gray matter volume. Previous hospital ICD10 diagnosis and antidepressant usage resulted in the most pronounced alterations. Conclusions and RelevanceLifetime exposure to depression is associated with robust functional changes with more restrictive criteria revealing more pronounced alterations. Different inclusion criteria for depression may strongly contribute to the substantial variation of imaging findings reported in the literature.