Sex-specific trajectories of inflammatory markers and depressive symptoms across adolescence: a 3-year follow-up study

Background

Depression in adolescence remains a major global challenge, and there is a need to better understand the biological mechanisms linked to changes in depressive symptoms over time. This is particularly important in low- and middle-income countries (LMICs) where most adolescents live and where limited research exists. Previous work from our group in a Brazilian adolescent cohort showed sex-specific associations between inflammatory markers and depression, with increased interleukin (IL)-2 associated with depressive symptoms in boys and increased IL-6 associated with depressive symptoms in girls [1]. Building on these findings, this study examined longitudinally whether changes in the levels of IL-2 and IL-6 were associated with changes in depressive symptoms over the course of 3 years in the same cohort of adolescents, and whether these associations differed by sex.

Methods

The sample consisted of N = 121 adolescents (boys N = 58 and girls N = 63) who were recruited from schools in Porto Alegre, Brazil, as part of the Identifying Depression Early in Adolescence Risk-Stratified Cohort (IDEA-RiSCo) and followed up over a 3-year period. Depressive symptoms were assessed at baseline and at the 3-year follow-up using Mood and Feelings Questionnaire (MFQ) – a self-report scale completed by adolescents. Serum IL-2 and IL-6 levels were measured at baseline and the 3-year follow-up, and change scores were calculated for each cytokine and for depressive symptoms across the 3-year period. Linear regression analyses were used to examine whether changes in IL-2 and IL-6 levels were associated with the changes in depressive symptoms over a 3-year period. Analyses were first conducted in the whole sample and then stratified by sex.

Results

Increase in IL-6 levels was associated with the increase in depressive symptoms over the 3-year follow-up (β = .22, p=.016). This association was driven by adolescent girls (β = .33, p=.009), whereas the same pattern was not observed in boys (β = -.006, p=.963). Changes in IL-2 levels were not associated with depressive symptom change in the whole sample or in sex-stratified analyses (all p>’s.40).

Conclusions

Our findings suggest that longitudinal links between inflammatory marker trajectories and depressive symptom trajectories across adolescence may differ by sex, with increases in IL-6 levels showing particular relevance in adolescent girls. These results extend our previous cross-sectional findings and support the importance of considering biological sex when investigating inflammatory predictors of adolescent depression. Further longitudinal studies in larger samples are needed to confirm these findings and clarify their clinical relevance.

Conflict of Interest and Acknowledgements:The authors declare no competing interests. Funding was provided by MQ Brighter Futures, the Royal Academy of Engineering, the UK Medical Research Council, the Academy of Medical Sciences, the National Institute of Mental Health, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul.

References

Zajkowska, Z., Nikkheslat, N., Manfro, P.H., Souza, L., Rohrsetzer, F., Viduani, A., Pereira, R., Piccin, J., Zonca, V., Walsh, A.E.L., Gullett, N., Fisher, H.L., Swartz, J.R., Kohrt, B.A., Kieling, C., Mondelli, V., 2023. Sex-specific inflammatory markers of risk and presence of depression in adolescents. J. Affect. Disord. 342, 69–75.