Sex-specific inflammatory markers of risk and presence of depression in adolescents

Zuzanna Zajkowska, Naghmeh Nikkheslat, Pedro H. Manfro, Laila Souza, Fernanda Rohrsetzer, Anna Viduani, Rivka Pereira, Jader Piccin, Valentina Zonca, Annabel Walsh, Nancy Gullett, Helen Fisher, Johnna R. Swartz, Brandon A Kohrt, Christian Kieling, Valeria Mondelli

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Associations between inflammatory markers and depression are reported among adults; however, less is known in adolescent depression in particular whether these associations are sex-specific. We aimed to identify inflammatory markers of increased risk and presence of depression in adolescence and their association with severity of depressive symptoms in the entire cohort and separately in boys and girls.
We measured serum cytokines using a Meso Scale Discovery electrochemiluminescence V-PLEX assay in a cohort of 150 adolescents stratified for risk/presence of depression. Risk group and sex-specific differences in inflammatory markers were assessed with 2-way mixed ANOVA, and sex-moderated associations between inflammatory markers and the severity of depressive symptoms were assessed with moderated multiple hierarchical regression analyses.
We found a significant interaction between biological sex and the risk group, where boys showed higher interleukin (IL)-2 levels among the depressed group compared with the low-risk group. The severity of depressive symptoms was associated with elevated levels of IL-2 in boys, and of IL-6 in girls. There was a significant moderating effect of sex on the relationship between IL-2 and the severity of depressive symptoms but not for IL-6.
The cross-sectional design means that we cannot be certain about the direction of the associations.
Our findings suggest sex-specific associations between inflammatory markers and the development of adolescent depression, where IL-2 may increase risk for depression and severity of depressive symptoms in boys, but not in girls. However, IL-6 may increase risk for more severe depressive symptoms in girls.
Original languageEnglish
Article numberJAD 16309
Pages (from-to)69-75
Number of pages7
JournalJournal of affective disorders
Early online date16 Jul 2023
Publication statusPublished - 1 Dec 2023


  • Depression
  • Cytokine
  • depressive symptoms
  • Adolescence
  • inflammation
  • Sex differences


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