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Association between cytokines and depressive symptoms in adolescents: gender and depressive symptom clusters
Yang Zhang1, Xingbo Suo2, Xinqi Wang1
1Department of Clinical Psychology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China.
Background:
Depressive disorders are prevalent in adolescents. Identifying the cytokines that are specifically associated with gender and symptom clusters in adolescent depressive disorders may help to advance personalized treatment.
Methods:
A cross-sectional study was conducted at Qilu Hospital of Shandong University (Qingdao) from January 2022 to April 2025, including 449 adolescents (aged 10-19) diagnosed with depressive disorders. The levels of twelve cytokines in serum were determined by multiplex immunofluorescence. Overall depressive symptoms and seven depressive symptom clusters were evaluated through the Hamilton Depression Scale 24-item. The relationships among cytokines, overall depressive symptoms, and symptom clusters were examined through linear regression and gender stratification. Statistical analysis and visualization were performed using R software (version 4.3.2).
Results:
Interleukin-2 (IL-2) was negatively associated with overall depressive symptoms in female adolescents, while no cytokines showed significant associations in males. Among female adolescents, the associations between cytokines and depressive symptom clusters were most prominent for the anxiety/somatization cluster (involving three cytokines: negative associations for IL-2 and interleukin-4 (IL-4), positive association for interleukin-12 subunit p70). In the total sample and female adolescents, the diurnal variation cluster (negative association for IL-4) and the retardation cluster (negative association for IL-2) demonstrated significant associations with cytokines. No significant associations were observed between depressive symptom clusters and any of the cytokines in male adolescents.
Conclusions:
Cytokines have a specific association with overall depressive symptoms and depressive symptom clusters in adolescents with depressive disorders, and the association is gender-specific.
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