Handgrip strength is associated with hippocampal volume and white matter hyperintensities in major depression and healthy controls: a U.K. Biobank study

Objectives: Emerging evidence suggests that handgrip strength (a proxy for muscular fitness) is associated with better cognitive performance in people with major depressive disorder (MDD). The underlying processes are unclear, although hippocampal volume (HCV) reductions and white matter hyperintensities (WMHs) have been implicated. Therefore, we investigated the associations between maximal handgrip strength and volume of various brain regions and WMHs in MDD and healthy controls (HCs). Methods: We conducted cross-sectional analysis of handgrip strength and neuroimaging data from the U.K. Biobank. Generalised linear models assessed the relationship between grip strength and grey matter, white matter, total brain volume, left and right hippocampus volume and WMHs in MDD and HCs, adjusting for age, sex, education and bodyweight. Results: The final sample included 527 people with MDD (54.3 years, 37.2% male) and 1764 HCs (56.6 years, 53% male). In MDD, stronger handgrip was significantly associated with increased left (Coefficient±S.E= 109.5±27.4) and right (76.6±30.2) HCV. In HCs, only right HCV related to handgrip strength (44.8±17.9). Interaction analyses found stronger associations between grip strength and HCV in MDD compared to HCs, for both hippocampal regions. Stronger handgrip was associated with reduced WMHs in people with MDD (-839.0±277.6) and HCs (-394.1±175.5). Maximal handgrip strength was not associated with grey matter, white matter or total brain volumes in either group. Conclusions: Stronger grip strength is associated with greater left and right HCV and reduced WMHs in MDD. Future research should investigate directionality and consider if interventions targeting strength/muscular fitness can improve brain health and reduce the neurocognitive abnormalities associated with MDD.