Combining neurobiological markers and a sociodemographic risk score to predict adolescent depression - An IDEA RiSCo prospective cohort study

The prevention of adolescent depression is a critical global challenge, hindered by the difficulty of identifying those at increased risk. We previously developed a sociodemographic-based risk score (IDEA-RS), which has proven to successfully predict depression onset in adolescents across five continents. This study aims to 1) improve the predictive accuracy by integrating biological and sociodemographic factors, and 2) generate a biological risk score, by combining biological information, to complement IDEA-RS. Derived from screening over 7000 adolescents aged 14-16 years old in Brazil, we recruited 100 adolescents representing the extremes of the sociodemographic risk score and including 50 adolescents at low-risk and 50 at high-risk of developing depression according to IDEA-RS. Baseline blood samples and fMRI scan were performed to measure selected biological markers: cytokines, kynurenine pathway metabolites and amygdala reactivity to negative stimuli. Adolescents were followed up over three years to identify those who would transition to develop depression. The primary outcome of depression incidence was assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). A composite biological risk score (IDEA-BIO-RS) was created incorporating the above biomarkers. Combining biological factors with IDEA-RS significantly improved the accuracy of predicting depression onset compared with IDEA-RS alone. Among adolescents classified as high-risk by both IDEA-RS and IDEA-BIO-RS, 44% developed depression over three years, while none of those classified as low-risk by both scores developed depression. This combined approach shows promise as a screening tool to identify adolescents at risk of developing depression and aid in prevention efforts.