Brain metabolic vulnerability in 18-F FDG PET/CT predict future depression risk in young cancer survivors

Adolescent and early young adult (AeYA) cancer survivors (aged 15-25 years) face elevated risks of depression following remission. Emerging evidence suggests that brain metabolic vulnerability, detectable via 18-F FDG PET/CT, may serve as a sentinel biomarker for latent depression risk. To investigate this hypothesis, we conducted a multicenter longitudinal study in two independent cohorts (n = 923 discovery, n = 518 validation) in which participants underwent sequential PET/CT scans and were followed for 3 years (mean follow-up: 29.58 ± 10.01 months). Reduced SUVmean values in the ventral prefrontal cortex, hippocampus, and amygdala predominantly predicted future depression onset after adjusting for clinical, psychosocial, and treatment-related confounders. A radiomic nomogram integrating these metabolic parameters demonstrated robust predictive accuracy (C-index: 0.91 discovery, 0.88 validation). By identifying neurobiological susceptibility years before symptom emergence, this study points to 18-F FDG PET/CT as a clinically actionable tool for preemptive depression risk stratification in AeYA survivors, thus repurposing 18F-FDG PET/CT from tumor management surveillance to preemptive depression risk screening.