Associations of childhood trauma with clinical features and inflammatory cytokines in adolescents with first-episode and recurrent major depressive disorder

Xi Zhang^1,2Lewei Liu¹Ruitong Li²Yun Zhang²Haojie Fan¹Mingru Hao¹Feng Geng³Mo Daming⁴Lei Xia^1*Huanzhong Liu^1,2,4*

• ¹Department of Psychiatry, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
• ²Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China
• ³Department of Psychology and Sleep Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
• ⁴Affiliated Psychological Hospital of Anhui Medical University, Hefei, China

Background: Childhood trauma is a significant risk factor for adolescents with major depressive disorder (MDD), but its associations with clinical features and inflammatory cytokines remain unclear across illness stages. This study aimed to investigate these associations by comparing adolescents with first-episode and recurrent MDD. Methods: We recruited 170 adolescents with MDD and 76 healthy controls (HCs) between January 2021 and December 2022. The Childhood Trauma Questionnaire (CTQ), the Center for the Epidemiological Studies Depression Scale (CES-D), the Positive and Negative Suicidal Ideation Scale (PANSI), and the 20-item Toronto Alexithymia Scale (TAS-20) were used to assess childhood trauma, severity of depression, suicidal ideation, and alexithymia. Plasma levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, and tumor necrosis factor-alpha (TNF-α) were determined by electrochemiluminescence. Results: The detection rate of childhood trauma was significantly higher in the MDD group than in HCs (80.59% vs. 31.58%). Patients also had significantly higher scores on all clinical scales and elevated levels of IL-1β, IL-6, IL-10, IL-17A, and TNF-α (all P < 0.001), except for IL-8 (P = 0.543). Correlation analysis revealed that in first-episode patients, CTQ scores were positively linked to scores of CES-D, PANSI, and TAS-20 and levels of IL-1β, IL-6, IL-10, and IL-17A. However, in the total sample and recurrent patients, CTQ scores correlated solely with clinical features. Further multivariate linear stepwise regression analysis revealed that in first-episode patients,CTQ scores were independently associated with CES-D scores (β = 0.396, t = 3.688, P < 0.001), PANSI scores (β = 0.519, t = 5.190, P < 0.001), TAS-20 scores (β = 0.454, t = 4.355, P < 0.001), and levels of IL-1β (β = 0.264, t = 2.336, P = 0.022), IL-6 (β = 0.228, t = 2.002, P = 0.049), IL-10 (β = 0.253, t = 2.233, P = 0.029), and IL-17A (β = 0.251, t = 2.215, P = 0.030). Conclusion: Childhood trauma is common in adolescents with MDD and associated with more severity of depression, suicidal ideation, and alexithymia. Its link to inflammatory cytokines is exclusively observed in first-episode patients, suggesting trauma-related immune activation may be particularly important in initial onset.