Association Between Psychoneurological Symptoms With Inflammatory Cytokines And Their Longitudinal Changes In Patients With Glioma

Objective:To investigate the incidence,severity,internal network structural characteristics and longitudinal changes of anxiety,depression,sleep disturbance,fatigue and pain during treatment of glioma patients,and to explore the inflammatory cytokines associated with the occurrence of psychoneurological symptoms to provide a theoretical basis for the precise management and intervention of psychoneurological symptoms during treatment of patients.Methods:The study was a longitudinal study design.Using a convenience sampling method,334 patients with glioma who were hospitalized in neurosurgery departments of two tertiary hospitals in Shandong Province from December 2020 to December 2022 were selected as the research participants.Questionnaires were administered using the General Information Questionnaire,the Hamilton Anxiety Inventory,the Hamilton Depression Inventory,the Pittsburgh Sleep Quality Index Scale,the Multidimensional Fatigue Scale,and the Pain Digital Rating Scale at 2-day after admission(T1),7-day postoperative(T2),and 1-month postoperative(T3).On the same day of the questionnaire survey at stage T1,the researchers drew venous blood from patients for laboratory tests to detect plasma interleukin-1β,interleukin-6,interleukin-10,tumor necrosis factor-α,and C-reactive protein concentrations by enzyme-linked immunosorbent assay.The main statistical methods included descriptive analysis,ANOVA test,and network analysis.Results:1.A total of 334 patients with glioma were investigated in this study,with a mean age of(54.3 8±13.16)years and a mean BMI of(24.65± 3.81)kg/m2,of whom 163(48.8%)were male and 171(51.2%)were female.According to WHO classification of glioma,110 patients(32.9%)had low-grade tumors,and 224 patients(67.1%)had high-grade tumors.According to imaging data and surgical records,53 patients(15.9%)had tumors in the temporal lobe,and 106 patients(31.7%)had tumors in the frontal lobe.The proportion of patients with tumors in the right side was higher(42.5%);41 patients(12.3%)had Karnofsky Performance Status(KPS)scores<60,and 293 patients(87.7%)had KPS scores≥ 60.2.The score of anxiety,depression,sleep disturbance,fatigue,and pain in patients with glioma at baseline(T1)was(13.53± 10.18),(11.26±7.76),(7.87±4.92),(57.30±13.65)and(4.90±2.66),respectively.The each psychoneurological symptom score of patients at 7-day postoperative(T2)was(13.48± 12.00),(14.18±10.13),(8.81 ±4.08),(65.62± 16.96),(3.40±2.92),and(3.40±2.92),respectively.The each psychoneurological symptom score of patients at 1month postoperative(T3)was(18.90±8.54),(10.08± 10.11),(11.44±3.51),(70.20± 10.79),and(3.19±2.46),respectively.Fatigue was the most prevalent psychoneurological symptom reported by patients during treatment.3.Network analysis was used to establish a symptom-cytokine network model,with age and body mass index included as covariates.Among the inflammatory cytokines included,IL6 had the highest strength of 0.87.IL-1β expression level was positively correlated with the sleep disorder dimension(0.14),IL-6 expression level was positively correlated with the anxiety/somatization dimension(0.13),and IL-10 expression level was negatively correlated with the anxiety/somatization dimension(-0.15).The internal structural networks of psychoneurological symptom dimensions in glioma patients from stages T1 to T3 were constructed separately.At stage T1,the comprehensive fatigue dimension,mental anxiety dimension,and sleep duration dimension were the core nodes in the network with strengths of 1.50,1.40,and 1.20,respectively.Network stability test revealed that the network centrality coefficient of strength was 0.594,indicating a good stability of the network model.At stage T2,the mental anxiety dimension,sleep duration dimension,and retardation dimension were the core nodes in the network,with strengths of 1.30,1.20,and 1.20,respectively.Network stability test revealed that the network centrality coefficient of strength was 0.749,indicating a high stability of the network model.At stage T3,the anxiety/somatization dimension,somatic anxiety dimension,and mental anxiety dimension were the core nodes in the network with strengths of 1.30,1.20,and 1.10,respectively.Network stability test revealed that the network centrality coefficient of strength was 0.518,indicating a good stability of the network model.4.The three stages network models were compared separately.In the comparison of the network models of stage T1 and stage T2,there was a statistical difference in network structure between the two networks(M=0.316,P<0.01).In terms of overall connection strength,the overall connection strength of the stage T1 network was 10.204,and the overall connection strength of the stage T2 network was 10.039,and there was no statistical difference between the two(GS=0.165,P=0.58).In the comparison of the network models of stage T1 and stage T3,there was a statistical difference in network structure between the two networks(M=0.368,P<0.01).In terms of overall connection strength,the overall connection strength of the stage T1 network was 10.204,and the overall connection strength of the stage T3 network was 8.592,and there was a statistical difference between the two(GS=1.612,P<0.01).In the comparison of the network models of stage T2 and stage T3,there was a statistical difference in network structure between the two(M=0.299,P<0.01).In terms of overall connection strength,the overall connection strength of the stage T2 network was 10.039,and the overall connection strength of the stage T3 network was 8.592,and there was a statistical difference between the two(GS=1.446,P<0.01).Conclusions:1.The incidence of anxiety,depression,sleep disturbance,fatigue,and pain were high in patients with glioma during treatment,with fatigue being the most prevalent symptom.2.The association of each dimension of anxiety,depression,sleep disturbance,fatigue,and pain with different inflammatory cytokines in glioma patients helps healthcare professionals understand more deeply the underlying biological mechanisms of psychoneurological symptom and provides a theoretical basis for effective clinical interventions.3.In psychoneurological symptoms,there is an interconnection among various symptom dimensions within the symptoms.At the early stage of admission,comprehensive fatigue(manifested as poor mental performance,feeling tired,insufficient rest,and easy fatigue,etc.)was the core dimension in the network;at 7-day postoperative stage,mental anxiety(manifested as worry,nervousness,fear,insomnia,etc.)was the core dimension in the network;at 1-month postoperative stage,anxiety/somatization(manifested as worry,dry mouth,bloating,diarrhea,frequent urination,sweating,etc.)was the core dimension in the network.