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Handgrip Strength Is Associated With Hippocampal Volume and White Matter Hyperintensities in Major Depression and
Josh A Firth1, Lee Smith, Jerome Sarris
1From the Department of Zoology, Edward Grey Institute (J.A. Firth), and Merton College (J.A. Firth), University of Oxford, Oxford; The Cambridge Centre for Sport and Exercise Sciences, Department of Life Sciences (Smith), Anglia Ruskin University, Cambridge, United Kingdom; NICM Health Research Institute, Western Sydney University (Sarris, J. Firth), Westmead; Department of Psychiatry (Sarris), University of Melbourne, The Melbourne Clinic, Melbourne, Australia; Department of Rehabilitation Sciences (Vancampfort), KU Leuven, Leuven, Belgium; Department of Sports Methods and Techniques, Federal University of Santa Maria (Schuch), Santa Maria, Brazil; Centre for Addiction and Mental Health (Carvalho), Toronto, Ontario, Canada; Department of Psychiatry (Carvalho), University of Toronto, Toronto, Ontario, Canada; Department of Neurosciences (Solmi), University of Padova; Local Health Unit 17 ULSS 17, Mental Health Department (Solmi), Padova, Italy; Physiotherapy Department (Yung, Stubbs), South London and Maudsley NHS Foundation Trust; Department of Psychological Medicine, Institute of Psychiatry (Yung, Stubbs), Psychology and Neuroscience, King's College London, London; Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health (J. Firth), University of Manchester, Manchester, United Kingdom; and Centre for Youth Mental Health, University of Melbourne (J. Firth), Melbourne, Australia.
Objective:
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 handgrip strength and various brain region volumes and WMHs in MDD and healthy controls (HCs).
Methods:
This study is a cross-sectional analysis of handgrip strength and neuroimaging data from the UK Biobank. Generalized linear models were used to assess the relationship between grip strength and gray matter, white matter, total brain volume, left and right hippocampus volume, and WMHs in MDD and HCs, adjusting for age, sex, education, and body weight.
Results:
The sample included 527 people with MDD (54.3 ± 7.3 years, 37.2% male) and 1764 HCs (56.6 ± 7.2 years, 53% male). In MDD, stronger handgrip was significantly associated with increased left (coefficient ± SE = 108.1 ± 27.6, t = 3.92) and right (76.8 ± 30.4, t = 2.53) HCV. In HCs, only right HCV related to handgrip strength (44.8 ± 18.1, t = 2.47). Interaction analyses found stronger associations between grip strength and HCV in MDD compared with HCs, for both hippocampal regions. Stronger handgrip was associated with reduced WMHs in people with MDD (-0.24 ± 0.07, t = -3.24) and HCs (-0.11 ± 0.04, t = -2.47). Maximal handgrip strength was not associated with gray 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.