A Follow-up Study On The Associations Of Plasma Inflammatory Cytokines With Mental Health Among College Students

Objectives The study aimed to describe the prevalence of multiple mental health and their trajectories among college students,and analyze the associations of plasma inflammatory cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)levels and the ratio of the sum of IL-6,IL-1β and TNF-α to IL-10 at baseline with multiple mental health at baseline,and examine the predictive effect of baseline plasma inflammatory cytokines on multiple mental health problems at follow-up,new-onset mental health problems after 6 and 12 months and the trajectory of mental health problems.Methods Participants were from the College Student Behavior and Health Cohort Study,which tracked the behavioral and health problems of college students in Hefei City,Anhui Province and Shangrao City,Jiangxi Province through electronic questionnaires in April 2019 and April 2021,with an interval of 6 months.Depression Anxiety Stress Scale-21(DASS-21)was used to assess depressive symptoms,anxiety symptoms and stress symptoms,and the Patient Health Questionnaire 9(PHQ-9)was used to assess the specificity of depressive symptoms in college students,while fasting venous blood was collected at baseline to measure the plasma inflammatory cytokines IL-1β,IL-6,TNF-α,and IL-10 levels.The latent variable growth curve models were used to analyze the trajectories of depressive symptoms,anxiety symptoms and stress symptoms,and binary logistic regressions were used to analyze the relationship between IL-6,IL-1β,TNF-α and IL-10 and the ratio of the sum of IL-6,IL-1β and TNF-α to IL-10 and multiple mental health problems and their trajectories at baseline,the 6-month follow-up and the 12-month follow-up.Results A total of 706 college students were included in our study,including 230 males(32.6%)and 476 females(67.4%).The mean age was 18.68±1.00 years at baseline.The rates of depressive symptoms were 17.1% at baseline,18.1% at the 6-month follow-up and 15.0% at the 12-month follow-up,respectively.The rates of anxiety symptoms were25.8% at baseline,22.2% at the 6-month follow-up and 14.7% at the 12-month follow-up,respectively.The rates of stress symptoms were 8.8% at baseline,8.5% at the6-month follow-up,and 5.4% at the 12-month follow-up,respectively.After adjusting for sex,self-reported family economic status,paternal education,smoking,alcohol consumption,physical activity,and sleep disorders,the results of binary logistic regression analysis revealed that higher levels of IL-10 were associated with decreased risks of depressive symptoms at the 6-month follow-up(OR=0.45,95%CI: 0.24-0.87),new-onset depressive symptoms after 6 months(OR=0.25,95%CI: 0.11-0.60)and the increased stress symptoms trajectory(OR=0.52,95%CI: 0.27-0.97).IL-1β levels were negatively associated with new-onset depressive symptoms after 6 months(OR=0.25,95%CI: 0.09-0.72).TNF-α levels were negatively associated with new-onset stress symptoms after 12 months(OR=0.17,95%CI: 0.03-0.94)and the increased stress symptoms trajectory(OR=0.31,95%CI: 0.12-0.79).The ratio of the sum of IL-1β,IL-6,TNF-α to IL-10 were positively correlated with depressive symptoms(OR=3.11,95%CI:1.25-7.74)and new-onset depressive symptoms after 6 months(OR=2.92,95%CI:1.13-7.54).After adjusting for sex,self-reported family economic status,paternal education,smoking,alcohol consumption,physical activity,and sleep disorders,binary logistic regression analysis revealed that the level of IL-10 was positively associated with anhedonia(OR=1.86,95%CI: 1.11-3.11)and fatigue(OR=2.01,95%CI: 1.19-3.40)at baseline;and negatively correlated to suicidal ideation after 6 months(OR=0.47,95%CI:0.23-0.97).The level of IL-1β was also positively associated with anhedonia(OR=2.23,95%CI: 1.19-4.17)and fatigue at baseline(OR=2.13,95%CI: 1.14-4.01).The level of TNF-α was positively associated with anhedonia at baseline(OR=2.28,95%CI:1.06-4.89).Higher IL-6 levels were associated with increased risks of sleep problems(OR=1.71,95%CI: 1.01-2.92)and fatigue after 6 months(OR=1.83,95%CI: 1.11-3.01),as well as sleep problems after 12 months(OR=2.02,95%CI: 1.11-3.67).The ratio of the sum of IL-1β,IL-6 and TNF-α to IL-10 was positively associated with psychomotor changes(OR=2.82,95%CI: 1.16-6.86)and suicidal ideation after 6 months(OR=3.25,95%CI: 1.28-8.26);it was also positively related to depressive mood(OR=2.73,95%CI:1.15-6.48),and sleep problems after 12 months(OR=3.25,95%CI: 1.24-8.51).Conclusions Mental health problems such as depressive symptoms,anxiety symptoms,stress symptoms were common among college students.The trajectories of mental health problems among college students during the 1-year follow-up was mainly manifested as increased and declined.Chronic inflammation is associated with the onset and progression of mental health problems during a 1-year follow-up,and it is also related to symptom-specificity of depressive symptoms such as anhedonia,depressive mood,sleep problems,fatigue,psychomotor changes,and suicidal ideation.More research with larger samples is wanted to verify the directivity of the associations between chronic inflammation and depressive symptoms.