Association of schizophrenia, major depression, and bipolar disorder with sarcopenia-related traits: a bidirectional two-sample Mendelian randomization study

Abstract

The rising incidence of schizophrenia, depression, bipolar disorder, and other mental illnesses have an association with sarcopenia (SP). Observational studies are susceptible to confounding factors. Mendelian randomization (MR) studies offer a way to mitigate the influence of such factors when assessing causality. The causal connection between schizophrenia, depression, bipolar disorder, and SP was evaluated using inverse-variance weighted (IVW) and other MR methods. Sensitivity analyses were also performed. We found schizophrenia exhibited a negative association with increased whole-body FFM (fat free mass) (odds ratio [OR] = 0.987, 95% CI: 0.979–0.996, P = 0.03), that was attributed to a reduction in FFM in both lower legs (OR = 0.990, 95% CI: 0.981–0.999, P = 0.037; OR = 0.984, 95% CI: 0.975–0.993, P = 0.000). Schizophrenia were negatively correlated in both upper limb, with OR = 0.987, 95% CI: 0.979–0.994, P = 0.001, OR = 0.986, 95% CI: 0.997–0.996, P = 0.004. Major depression and walking pace were negatively related (OR = 0.965, 95% CI: 0.935–0.996, P = 0.027). Bipolar disorder was associated with decreased left leg FFM (OR = 0.979, 95% CI: 0.960–0.999, P = 0.036). Both upper limbs showed a reduction in FFM, with the left and right limbs having an OR = 0.973, 95% CI: 0.953–0.993, P = 0.008 and OR = 0.973, 95% CI: 0.951–0.994, P = 0.014, respectively. Additionally, bipolar disorder was associated with increased walking pace (OR = 1.021, 95% CI: 1.005–1.038, P = 0.012).A potential causal relationship existed among SP-related traits, schizophrenia, and major depression, in addition to bipolar disorder. In conclusion, significant causal relationships exist between schizophrenia, major depression, bipolar disorder, and SP. SP worsens with the increasing severity of mental illness. SP demonstrated a potential causal relationship with schizophrenia and major depression, apart from bipolar disorder.