Neuroimmune Mechanism Of Depressive Symptoms In Schizophrenia

Background and objective: Depressive symptom is one of the core symptoms in schizophrenia,which is independent of the positive symptoms,negative symptoms and cognitive impairment,and it may occur at any time in the course of schizophrenia.The appearance of depressive symptoms may cause poor outcome and even increase suicide risk.Yet despite information concerning the epidemiology,symptoms and risk factors of the depressive symptoms are well documented,the etiology and pathophysiology of depression are not completely elucidated.Recently,the neuroimmune mechanisms of schizophrenia and depression have received much attention.Hence,the aim of the present study was to investigate the association between neuroimmune index(including cytokines,BDNF and SIRT1)and depressive symptoms in schizophrenia patients and to further explore the risk factors for depressive symptom in schizophrenia.Methods: A total of 174 patients and 29 controls were included in the present crosssection study.Significant depressive symptoms were defined by the cut-off score of 7or more on Calgary Depression Rating Scale(CDSS).The Positive and Negative syndrome scale(PANSS)was used to evaluate the severity of the psychotic symptoms and the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)for cognitive function in schizophrenia patients.Plasma levels of IL-α,IL-β,IL-4,IL-6,IL-8,IL-10,IL-13,MCP-1,IFN-γ,TNF-α,IL-17 A,BDNF and SIRT1,were measured by the enzyme-linked immunosorbent assay(ELISA)or Quantibody Human Inflammation Array 1(QAH-INF-1).We first compared the demographics,clinical symptoms and neuro-immune index between patients and health controls,as well as patients with and without depression.We then used Correlation analysis(Pearson or Spearman)and regression analysis(linear or logistic regression)to identify risk factors for depressive symptoms in schizophrenia.Since suicide is the most dangerous symptom item in depression,we further divided the patients into the groups with and without suicidal ideation,and discussed the differences in biological indicators between these two groups and explored the risk factors of suicidal ideation.Results: There was no significant differences in age,sex,education,marital status or body mass index(BMI)between schizophrenia patients and controls(P > 0.05).Our results showed that patients had a notably higher IL-1α(Z = 4.432,P < 0.001)、IL-6(Z = 2.780,P = 0.005)、IL-8(Z = 2.784,P = 0.005)、TNF-α(Z = 2.163,P = 0.030)levels and lower BDNF(Z = 7.406,P < 0.001)levels compared to controls.The occurrence rate for depressive symptoms in schizophrenia patients is around 43.68%.patients with depression(n= 64)had more severe psychotic symptoms evaluated by PANSS(high total and subscale scores)and also had poorer cognitive function exposed by the scale of RBANS(lower total and subscale scores)compared to patients without depression(n = 74)(P < 0.05).While no significant differences no significant difference in demographic data such as age,gender,education,marital status and BMI,as well as clinical data in age at the first onset,total disease course,family history of mental illness and use of antipsychotics these two groups(all P >0.05).Our results showed that patients with depressive symptoms had lower plasma levels of IL-10(Z=2.088,P = 0.037),BDNF(Z = 9.423,P < 0.001)and SIRT1(Z=7.311,P < 0.001).Interestingly,there was a significant positive correlation between the BDNF and SIRT1 levels in patients(r = 0.565,P < 0.001).After corrected by Bonferroni,our results showed that BDNF levels were higher in control groups than in patients with or without depression groups(Bonferroni corrected P <?0.001),and patients with depression also had higher BDNF levels than that in patients without depression(Bonferroni corrected P <?0.001).In regard to SIRT1,the levels in patients with depression was lower than that in the patients without depression or control groups(Bonferroni corrected P?<?0.05),but no difference between patients without depression and control group(Bonferroni corrected P > 0.05).However,the difference in plasma IL-10 levels among these three groups was not significant after Bonferroni corrected(P > 0.05).And our regression analysis showed that PANSS-G,PANSS-N,attention and delayed memory in RBANS,BDNF and SIRT1 were independent risk factors for depressive symptoms in schizophrenia.In addition,we further found that the rate of suicidal ideation(SI)in schizophrenia was 14.94%,patients with SI had a remarkably lower levels of BDNF than these without SI(Z = 9.423,P = 0.002),while no other differences were observed regarding to other biological parameters,as well as demographic and clinical data(P > 0.05).Our correlation analysis indicated that visuospatial skill in RBANS(r = 0.162,P = 0.036)was positively and BNDF levels(r=-0.266,P = 0.002)was negatively correlated with the severity of SI.Conclusions: Our findings provided evidence suggesting that the plasma BDNF levels are associated not only with schizophrenia but also with depressive symptoms and SI in patients with schizophrenia.In addition,the interaction between BDNF and SIRT1 may be responsible for the exacerbation of depressive symptoms in schizophrenia.Patients with depressive symptoms had more severe psychiatric symptoms and poorer cognitive function,and PANSS-negative symptoms,PANSSGeneral psychopathology,attention and delayed memory in RBANS,BDNF and SIRT1 levels were independent risk factors for depressive symptoms in schizophrenia.However,better cognitive function especially visuospatial skill may predict a more serious SI in schizophrenia.And our study failed to found any association between inflammatory cytokines and depressive symptoms or SI in schizophrenia patients.