Whether depression and poor sleep interact or have statistically independent associations with brain structure and its change over time is not known. Within a subset of UK Biobank participants with neuroimaging and subjective and/or objective sleep data (n = 28,351), we examined associations between lifetime depression and sleep disruption, and their interaction with structural neuroimaging measures, both cross-sectionally and longitudinally. Sleep variables were: self-reported insomnia and difficulty getting up
actigraphy-derived short sleep (<
7 h)
sustained inactivity bouts during daytime (SIBD)
and sleep efficiency. Imaging measures were white matter microstructure, subcortical volumes, cortical thickness and surface area of 24 cortical regions of interest. Individuals with lifetime depression (self-reported, mental health questionnaire or health records) were contrasted with healthy controls. Interactions between depression and difficulty getting up for i) right nucleus accumbens volume and ii) mean diffusivity of forceps minor, reflected a larger negative association of poor sleep in the presence vs. absence of depression. Depression was associated with widespread reductions in white matter integrity. Depression, higher SIBD and difficulty getting up were individually associated with smaller cortical volumes and surface area, particularly in the frontal and parietal lobes. Many regions showed age-related decline, but this was not exacerbated by either depression or sleep disturbance. Overall, we identified widespread cross-sectional associations of both lifetime depression and sleep measures with brain structure. Findings were more consistent with additive rather than synergistic effects - although in some regions we observed greater magnitude of deleterious associations from poor sleep phenotypes in the presence of depression.