Depressive disorder in middle-aged and elderly adults: Evidence from global burden of disease and genetic analysis

BACKGROUND: Growing evidence highlights accelerated biological aging as a potential mediator linking mental disorders morbidity and reduced healthy life expectancy. METHODS: We employed the Global Burden of Disease (GBD) cross-sectional study combined with Mendelian randomization (MR) analysis to investigate the aging-related trends in mental disorders. Leveraging the comprehensive GBD 2021 data, we conducted an in-depth analysis of global trends in incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and years lived with disability (YLDs) from 1990 to 2021. The global burden of YLDs due to psychiatric and depressive disorders has been quantified using age-period-cohort (APC), join-point regression and Bayesian models. Bidirectional two-sample MR analyses were performed to assess causal relationships between depressive disorders and biological aging. Biological aging phenotypes included leukocyte telomere length (TL) and a multidimensional index (MV-Age), which integrates parental lifespan, healthspan, extreme longevity, frailty, and epigenetic aging. RESULTS: YLDs from depressive disorders increased from 6.246 million (95 % UI: 4.253, 8.416 million) to 14.829 million (95 % UI: 10.252, 20.070 million), while YLDs from all mental disorders rose from 14.021 million (95 % UI: 10.448, 17.858 million) to 32.477 million (95 % UI: 24.204, 41.331 million). Among adults 55⁺ years, females maintained higher absolute rates, while males showed a steeper proportional increase (AAPC: 0.326 vs. 0.282), indicating a narrowing sex gap in late-life incidence. MR analyses revealed the potential bidirectional causal associations between depressive disorders and biological aging indexes: depressive disorders were associated with accelerated biological aging, as reflected by lower MV-Age (OR = 0.924, 95 %CI: 0.913-0.935, P = 1.53 × 10⁻³⁹) and by shorter telomere length (OR = 0.950, 95 %CI: 0.932-0.969, P = 1.94 × 10⁻⁷). Conversely, higher MV-Age was associated with a reduced risk of depressive disorders (OR = 0.654, 95 %CI: 0.535-0.799, P = 3.34 × 10⁻⁵). CONCLUSION: These results analyze global trends in mental disorders among middle-aged and older adults, highlighting the importance of targeting aging pathways to promote healthier lifespans and mitigate the impact of mental health conditions. The synthesis of GBD database combined with MR findings offered a nuanced understanding of the total mental disorders in middle and older age.