The causal relationship of depression, anxiety, and neuroticism with main indicators of sarcopenia: A Mendelian randomization study

Abstract

Background: Observational studies have shown the relationship between sarcopenia and psychiatric disorders. However, due to the limitations of traditional research methods, the causal relationship between them has not been accurately concluded. At the same time, considering that sarcopenia is mainly manifested by low muscle strength and low muscle mass, we used Mendelian randomization (MR) analysis in this study to explore the causal relationship of anxiety, depression, and neuroticism with muscle strength and muscle mass, respectively.

Methods: Genetic variants associated with depression were obtained from FinnGen Biobank (Ncase = 33,812, Ncontrol = 271,380), those associated with anxiety were from FinnGen Biobank (Ncase = 21,519, Ncontrol = 307,558), and those associated with neuroticism, including 12 items, were from a large-scale genome-wide association study (N range: 366,301-375,913). Muscle strength was represented by the hand grip strength (HGS), and muscle mass was represented by the appendicular lean mass (ALM) and the body fat percentage. The inverse-variance weighted (IVW) method was used as the primary analysis method, and the Mendelian Randomization Egger (MR-Egger) and the weighted median were used as supplementary methods to test whether the three psychological factors were causally related to these two main indicators of sarcopenia severity.

Results: Depression and neuroticism had different degrees of causal influence on muscle mass and strength, which was statistically significant. Specifically, the depression predicted by genes was significantly associated with ALM (beta = -0.043, p = 0.027), low hand grip strength (LHGS, measured for people of 60 years and older) (odds ratio (OR) = 1.129 (1.019-1.251), p = 0.019), right HGS (beta = -0.050, p = 0.001), left HGS (beta = -0.06, p = 0.001), and body fat percentage (beta = 0.035, p = 0.0138). The neuroticism predicted by genes was significantly associated with ALM (beta = -0.073, p = 0.034), LHGS (OR = 1.222 (1.085-1.377), p = 0.001), right HGS (beta = -0.058, p = 0.000), left HGS (beta = -0.080, p < 0.000), and body fat percentage (beta = 0.063, p = 0.008). However, anxiety was only significantly associated with LHGS (OR = 1.215 (1.008-1.465), p = 0.041) but not significantly associated with ALM (beta = 0.033, p = 0.313), right HGS (beta = -0.008, p = 0.678), left HGS (beta = 0.007, p = 0.712), or body fat percentage (beta = 0.022, p = 0.559).

Conclusion: This study supported the causal association of depression and neuroticism with muscle strength and mass, which are the two main indicators of sarcopenia. At the same time, there was no sufficient evidence for the causal relationship between anxiety and muscle strength or mass. The results of this study pointed to the need to intervene in the mental health of the elderly to prevent sarcopenia or reduce its severity.

Keywords: Mendelian randomization; anxiety; depression; muscle mass; muscle strength; neuroticism.