From the national data of CHARLS, we found that after controlling for potential confounders, older adults with the highest HGS had a 54% lower risk of depression than those with the lowest HGS (OR: 0.46; 95% CI: 0.35 to 0.61). Further exploratory investigations showed that this association was independent of age, marriage, BMI, sleep duration, and comorbidity, but there may be an interaction with gender, which allows the association between HGS and depression in older adults to be established. Further analysis revealed a significant negative bidirectional association between HGS and depression in community-dwelling older adults.
Comparison with other studies
Similar to a recent cross-sectional study on hospitalized older adults in China, there was a non-linear relationship between HGS and depression in community-dwelling older adults 15. Another survey of middle-aged and older adults in 18 European countries showed that men and women in the second, third, and fourth quartiles of HGS were less likely to have depressive symptoms than men and women in the first quartile of HGS. This is consistent with our study. The difference is that the study by Marques A et al. 21 used the HGS thresholds delineated by the European Working Group on Sarcopenia in Older People (i.e., HGS < 30 kg in men and < 20 kg in women), whereas our study was based on the Asian Working Group on Muscular Dystrophy. The low HGS cut-offs across geographic regions still yielded similar results, reinforcing the negative association between handgrip strength and depression. In addition, Marques A et al. 22 conducted a pooling of evidence that included the results of a systematic review of 21 studies suggesting a positive effect of muscle strength on reducing depression, and a meta-analysis also reported an inverse association between muscle strength and depression (OR: 0.85; 95% CI: 0.80 to 0.89). Moreover, in a large cohort study, Kandola AA et al. 23 with a 7-year follow-up of 152,978 United Kingdom Biobank participants, Low and medium HGS was associated with 1.410 (95% CI: 1.335 to 1.490) and 1.126 (95% CI: 1.066 to 1.189) higher odds of the common mental disorder compared to high HGS. Interestingly, an interaction between gender and HGS and depression was found in the exploratory analysis of this study. The potential reason may be that sex hormone levels (e.g., testosterone and estrogen) play a crucial role in muscle development, and differences in estrogen concentrations between the sexes may explain this interaction effect.
In exploring the bidirectional association between HGS and depression in older adults, a previous analysis of data from 17,713 older Americans by Luo et al. showed that every 5 kg decrease in HGS was associated with a 6% (95% CI: 3–9%) increase in the risk of depression 24. Conversely, depression may be associated with a 0.33 kg (95% CI: 0.09 to 0.56) decrease in HGS. The present study makes the bidirectional relationship between HGS and depression in older adults more reliable.
Possible explanations and implications
The negative association of HGS with depression can be explained by the fact that, on the one hand, low HGS leads to a limitation of motor function in individuals, as well as to physical weakness and reduced physical activity, inducing inflammation, especially in older age groups 25,26. The inflammatory factor theory suggests that the inflammatory response in the body occurs with the production of large amounts of cytokines that promote the inflammatory response, such as interleukins and tumor apoptotic factors, which enter the brain and affect neurotransmitters, neuromodulators, or neural circuits related to mood-emotion regulation, thus producing the symptoms of depression 27,28. On the other hand, HGS is a key indicator for assessing sarcopenia, a risk factor for increased depression 29.
With this in mind, the current study has several clinical implications. Since HGS predicts the onset of depression, routine screening for HGS should be incorporated into the prevention and management process of depression. More importantly, HGS can be reversed or maintained by exercise training. Meta-analyses based on randomized control trials have shown that aerobic and resistance training is beneficial in improving HGS 30–33. Several cohort studies have also demonstrated the benefits of physical activity for depression 34–36. Therefore, promoting physical activity in people at high risk for depression is a public health issue that needs appropriate attention and intervention.
Limitations
First, because it is a cross-sectional study, this study cannot infer causality. Second, given that the CESD is a self-report questionnaire, the diagnosis of depression may not be very accurate. Third, although we considered some of the confounding factors associated with depression, we did not consider inflammatory factors included, which are important indicators of the occurrence of depression. However, the negative association of HGS with depression remained in the study by Wu et al. after correction for inflammatory markers (C-reactive protein) 37. Fourth, due to the high number of missing HGS retest data from CHARLS, we included only the first measurement, which may have overestimated the association between HGS and depression.