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Major Depressive Disorder (MDD) has a prevalence of 11% by the end of adolescence and 90% of adolescents live in low and middle income countries (LMIC). Hence, identifying biomarkers to early identify adolescents at risk of developing the disorder is of paramount importance. A risk-stratified cohort of 150 adolescents was recruited in Porto Alegre (Brazil) by using the risk score developed by the IDEA (Identifying Depression Early in Adolescence) project. The cohort is comprised of 50 adolescents with a current diagnosis of MDD, 50 at high- and 50 at low-risk of developing MDD. Genome-wide gene expression analysis was performed and raw data processed for bioinformatic analysis. The comparison between depressed and high-risk adolescents showed the highest difference in terms of genes differentially modulated (FC > |1.2|, p<0.05); the pathways analysis showed the modulation of biological signatures associated with inflammation and immune system in the MDD group compared with both high- and low-risk groups. Alteration in inflammatory pathways are associated with the presence of MDD in adolescence but have not been observed in adolescents at risk of MDD. [ABSTRACT FROM AUTHOR]