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The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression

Author

Listed:
  • Rongtao Jiang

    (Yale School of Medicine)

  • Stephanie Noble

    (Northeastern University
    Northeastern University
    Northeastern University)

  • Matthew Rosenblatt

    (Yale University)

  • Wei Dai

    (Yale University)

  • Jean Ye

    (Yale University)

  • Shu Liu

    (University of Amsterdam
    Amsterdam Neuroscience)

  • Shile Qi

    (Georgia State University, Georgia Institute of Technology, and Emory University)

  • Vince D. Calhoun

    (Georgia State University, Georgia Institute of Technology, and Emory University)

  • Jing Sui

    (Beijing Normal University)

  • Dustin Scheinost

    (Yale School of Medicine
    Yale University
    Yale University
    Yale University)

Abstract

Cross-sectional studies have demonstrated strong associations between physical frailty and depression. However, the evidence from prospective studies is limited. Here, we analyze data of 352,277 participants from UK Biobank with 12.25-year follow-up. Compared with non-frail individuals, pre-frail and frail individuals have increased risk for incident depression independent of many putative confounds. Altogether, pre-frail and frail individuals account for 20.58% and 13.16% of depression cases by population attributable fraction analyses. Higher risks are observed in males and individuals younger than 65 years than their counterparts. Mendelian randomization analyses support a potential causal effect of frailty on depression. Associations are also observed between inflammatory markers, brain volumes, and incident depression. Moreover, these regional brain volumes and three inflammatory markers—C-reactive protein, neutrophils, and leukocytes—significantly mediate associations between frailty and depression. Given the scarcity of curative treatment for depression and the high disease burden, identifying potential modifiable risk factors of depression, such as frailty, is needed.

Suggested Citation

  • Rongtao Jiang & Stephanie Noble & Matthew Rosenblatt & Wei Dai & Jean Ye & Shu Liu & Shile Qi & Vince D. Calhoun & Jing Sui & Dustin Scheinost, 2024. "The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48827-8
    DOI: 10.1038/s41467-024-48827-8
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    References listed on IDEAS

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    1. Andres Gil-Salcedo & Aline Dugravot & Aurore Fayosse & Julien Dumurgier & Kim Bouillon & Alexis Schnitzler & Mika Kivimäki & Archana Singh-Manoux & Séverine Sabia, 2020. "Healthy behaviors at age 50 years and frailty at older ages in a 20-year follow-up of the UK Whitehall II cohort: A longitudinal study," PLOS Medicine, Public Library of Science, vol. 17(7), pages 1-19, July.
    2. Weikang Gong & Edmund T. Rolls & Jingnan Du & Jianfeng Feng & Wei Cheng, 2021. "Brain structure is linked to the association between family environment and behavioral problems in children in the ABCD study," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Remi Daviet & Gökhan Aydogan & Kanchana Jagannathan & Nathaniel Spilka & Philipp D. Koellinger & Henry R. Kranzler & Gideon Nave & Reagan R. Wetherill, 2022. "Associations between alcohol consumption and gray and white matter volumes in the UK Biobank," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    5. Kerri Smith, 2014. "Mental health: A world of depression," Nature, Nature, vol. 515(7526), pages 180-181, November.
    6. Ho, Daniel & Imai, Kosuke & King, Gary & Stuart, Elizabeth A., 2011. "MatchIt: Nonparametric Preprocessing for Parametric Causal Inference," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 42(i08).
    7. Priscila Marconcin & Sharon Barak & Gerson Ferrari & Élvio R. Gouveia & Marcelo de Maio Nascimento & Renata Willig & Margarida Varela & Adilson Marques, 2022. "Prevalence of Frailty and Its Association with Depressive Symptoms among European Older Adults from 17 Countries: A 5-Year Longitudinal Study," IJERPH, MDPI, vol. 19(21), pages 1-11, October.
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