Association of Peripheral Inflammatory Biomarkers and Growth Factors Levels with Sex, Therapy and Other Clinical Factors in Schizophrenia and Patient Stratification Based on These Data

Abstract

Multiple lines of evidence are known to confirm the pro-inflammatory state of some patients with schizophrenia and the involvement of inflammatory mechanisms in the pathogenesis of psychosis. The concentration of peripheral biomarkers is associated with the severity of inflammation and can be used for patient stratification. Here, we analyzed changes in serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-21, APRIL, BAFF, PBEF/Visfatin, IFN-α, and TNF-α) and growth/neurotrophic factors (GM-CSF, NRG1-β1, NGF-β, and GDNF) in patients with schizophrenia in an exacerbation phase. IL-1β, IL-2, IL-4, IL-6, BAFF, IFN-α, GM-CSF, NRG1-β1, and GDNF increased but TNF-α and NGF-β decreased in schizophrenia compared to healthy individuals. Subgroup analysis revealed the effect of sex, prevalent symptoms, and type of antipsychotic therapy on biomarker levels. Females, patients with predominantly negative symptoms, and those taking atypical antipsychotics had a more pro-inflammatory phenotype. Using cluster analysis, we classified participants into “high” and “low inflammation” subgroups. However, no differences were found in the clinical data of patients in these subgroups. Nevertheless, more patients (17% to 25.5%) than healthy donors (8.6% to 14.3%) had evidence of a pro-inflammatory condition depending on the clustering approach used. Such patients may benefit from personalized anti-inflammatory therapy.

Biochemical, Hematological, Inflammatory, and Gut Permeability Biomarkers in Patients with Alcohol Withdrawal Syndrome with and without Delirium Tremens

“…A p-value of less than 0.05 was considered to be statistically significant. K-means clustering was used to classify patients and healthy individuals into two clusters/subgroups with signs of high and low inflammation, as previously described [39]. Clustering was based on data from the following inflammatory biomarkers: WBC count, PLT count, ESR, and PLR.…”

Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder

“…Accumulated data indicate that mental disorders are accompanied by changes in cytokine levels. For example, the anti-inflammatory cytokine IL-2 is altered in people with schizophrenia [63,84,85]; IL-6 concentrations are associated with depression [42,45,86]; elevated levels of IL-6 are trait markers for BD [87] and schizophrenia [63,88]; elevations of IL-8 in cerebrospinal fluid are seen in patients with schizophrenia [89]; IL-18 is increased in patients with depression [50,61]; the level of TNF-α increased in patients with SCZ, MDD [63] and BD [90]. It is important to note that changes in the expression of cytokine genes may be conditioned by the presence of a range of specific polymorphic variants [64].…”

Anti-Inflammatory Effects of Peripheral Dopamine

“…The risk of acute and chronic kidney disease is increased in schizophrenic patients and also increases with the use of both typical and atypical antipsychotics [ 209 , 210 ]. Moreover, patients treated with several atypical antipsychotics have higher levels of cytokines and chemokines and are at higher risk of acute kidney injury than those treated with typical antipsychotics [ 211 , 212 , 213 ]. This is not a general finding, as the anti-inflammatory effect of an atypical antipsychotic has also been reported for risperidone with no anti-inflammatory effect of clozapine [ 214 ].…”