Genetic predisposition to combined depression and cardiometabolic disease creates detectable biological signatures decades before symptoms appear. Analyzing 5,821 participants in the landmark ALSPAC birth cohort, researchers tracked children from age 9 to 24 and found those with higher polygenic risk scores showed elevated inflammatory markers—particularly interleukin-6, TNFSF14, and hepatocyte growth factor—at both childhood and young adult timepoints. These same individuals exhibited worsening trajectories for depressive symptoms and metabolic markers over the 15-year follow-up period. The inflammatory signature suggests that genetic liability to adult internalizing-cardiometabolic multimorbidity operates through immune dysregulation that begins in childhood, potentially seeding tissue inflammation that later manifests as clinical disease. This represents a significant advance in understanding how psychiatric and metabolic conditions share biological pathways from early development. The findings could enable earlier identification of high-risk individuals, though the observational design cannot establish causation. As this work is a preprint awaiting peer review, these inflammatory biomarker patterns require validation before clinical application. If confirmed, childhood IL-6 levels might serve as early intervention targets for preventing adult multimorbidity.