Objective: To investigate the changes of serum neuropeptide Y (NPY), 5-hydroxytryptophan (5-HT) and brain-derived neurotrophic factor (BDNF) in first-episode generalized anxiety disorder (GAD) of adolescents with different anxiety levels and their correlation with life stress, inflammatory factors and memory function. Methods: 147 adolescent first-episode GAD patients who were admitted to Chengdu mental health center from January 2019 to December 2021 were selected, and they were divided into mild anxiety group (5-9 scores, 50 cases), moderate anxiety group (10-14 scores, 65 cases) and severe anxiety group (15-21 scores, 32 cases) according to the Generalized Anxiety Scale (GAD-7). Serum levels of NPY, 5-HT, BDNF, C-reactive protein (CRP), interleukin (IL) -1αand IL-6 were detected. Students’ Life Stress Inventory (SLSI) and delayed matching test (DMS) were used to evaluate the life stress level and memory function. The levels of serum NPY, 5-HT, BDNF, CRP, IL-1α and IL-6 as well as SLSI and DMS were compared between groups, and the correlation between serum levels of serum NPY, 5-HT and BDNF and levels of serum CRP, IL-1α and IL-6 as well as SLSI and DMS were analyzed. Results: The levels of serum NPY, 5-HT and BDNF in severe anxiety group were lower than those in moderate anxiety group and mild anxiety group (P<0.05), and the moderate anxiety group was lower than the mild anxiety group (P<0.05). The levels of CRP, IL-1α and IL-6 and SLSI score in severe anxiety group were higher than those in moderate anxiety group and mild anxiety group (P<0.05). The moderate anxiety group was higher than the mild anxiety group (P<0.05). The total delayed response time and no delayed response time in the severe anxiety group were longer than those in the moderate anxiety group and the mild anxiety group (P<0.05), and the moderate anxiety group was longer than the mild anxiety group (P<0.05). The total delayed correct number and no delayed correct number in severe anxiety group were less than those in moderate anxiety group and mild anxiety group (P<0.05),and the moderate anxiety group was less than the mild anxiety group (P<0.05). The levels of serum NPY, 5-HT and BDNF were negatively correlated with SLSI score, CRP, IL-1α, IL-6, total delayed response time and no delayed response time (P<0.05), and positively correlated with total delayed correct number and no delayed correct number (P<0.05). Conclusion: With the aggravation of anxiety, life stress intensity, inflammatory factor level and memory function of adolescent first-episode GAD patients are enhanced, and all of them are related to the decrease of the levels of serum NPY, 5-HT and BDNF. [ABSTRACT FROM AUTHOR]