To explore the correlation between peripheral plasma cytokine levels and disease severity in adolescents with first-episode and recurrent depression.

Clinical data were prospectively collected on a total of 134 adolescents with depression, including 36 males and 98 females, aged 12-18 (15.3±1.5) years, who were either the outpatients or the inpatients in the Department of Psychiatry of Chaohu Hospital of Anhui Medical University and the Hefei Fourth People′s Hospital from October 2020 to March 2022. Patients were classified into 76 first-episode depression (first-episode group) and 58 recurrent depression (recurrent group) according to whether the depressive symptoms were in their first episode or not. During the same period, 76 age-matched healthy controls (health controls group) were recruited, including 45 males and 31 females, aged 12-18 (15.1±1.8) years. The 24-item Hamilton Depression Scale (HAMD₂₄) was used to assess the severity of depression in the patients, and a total HAMD₂₄ score of 35 was used as the cutoff point to classify the depressive patients into mild-to-moderate (52 patients) and severe depression (24 patients). Plasma interleukin (IL)-10, IL-17A, IL-1β, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) levels of patients were measured using meso scale discovery. Spearman correlation analysis was used to analyze the relationship between cytokine levels and disease severity in patients with depression; multiple linear regression was used to analyze the factors influencing disease severity in the first-episode group, and binary logistic regression was used to analyze the risk factors in severely ill patients in the first-episode group.

Comparison of plasma IL-1β, IL-6 and TNF-α (H=6.46, 6.75, 6.41, all P<0.05) levels between the 3 groups of subjects showed statistically significant differences; posthoc analysis showed no statistically significant differences in plasma cytokine levels between the first-episode group and the recurrent group(all P>0.05); the plasma IL-6 levels in the first-episode group were significantly higher compared with the healthy controls [M(Q₁, Q₃)] [1.69 (1.17, 2.45) ng/L vs 1.34 (1.05, 2.06) ng/L, Z=-2.67, P_{Bonferroni correction}=0.030]. Spearman correlation analysis showed a positive correlation between the HAMD-24 total score and the levels of IL-17A, IL-1β, IL-6, and TNF-α (r=0.275, 0.260, 0.300, 0.331, all P<0.05) in the first-episode group, and no correlation was found between the HAMD₂₄ total score and any cytokine in the recurrent group. In the first-episode group, plasma IL-10, IL-17A, IL-1β, IL-6, and TNF-α levels were significantly higher in severely ill patients compared to mildly/moderately ill patients[0.48 (0.33, 0.72) ng/L vs 0.63 (0.46, 1.10) ng/L, 1.89 (1.22, 3.04) ng/L vs 3.01 (1.94, 5.18) ng/L, 0.17 (0.12, 0.36) ng/L vs 0.42 (0.22, 0.65) ng/L, 1.55 (1.12, 2.05) ng/L vs 2.30 (1.68, 3.75) ng/L, 0.92 (0.77, 1.38) ng/L vs 1.42 (0.95, 2.15) ng/L respectively, all P<0.05]. Both multiple linear regression and binary logistic regression analyses showed that LgIL-6 level was independently associated with the severity of disease (multiple linear regression: β=2.550,95%CI:1.258-10.724,P<0.05; binary logistic regression: OR=12.499,95%CI:2.061-75.806,P<0.05).

Higher levels of plasma IL-6 correlate with more severe depressive symptoms in adolescents with first-episode depressive disorder and are a risk factor for severely ill patients with depression.

Depressive disorder; Adolescents; First-episode; Recurrent; Cytokines; Disease severity