Identification of Diagnostic Schizophrenia Biomarkers Based on the Assessment of Immune and Systemic Inflammation Parameters Using Machine Learning Modeling.

Disorders of systemic immunity and immune processes in the brain have now been shown to play an essential role in the development and progression of schizophrenia. Nevertheless, only a few works were devoted to the study of some immune parameters to objectify the diagnosis by means of machine learning. At the same time, machine learning methods have not yet been applied to a set of data fully reflecting systemic characteristics of the immune status (parameters of adaptive immunity, the level of inflammatory markers, the content of major cytokines). Considering a complex nature of immune system disorders in schizophrenia, incorporation of a broad panel of immunological data into machine learning models is promising for improving classification accuracy and identifying the parameters reflecting the immune disorders typical for the majority of patients. The aim of the study is to assess the possibility of using immunological parameters to objectify the diagnosis of schizophrenia applying machine learning models.

Materials and methods: We have analyzed 17 immunological parameters in 63 schizophrenia patients and 36 healthy volunteers. The parameters of humoral immunity, systemic level of the key cytokines of adaptive immunity, anti-inflammatory and pro-inflammatory cytokines, and other inflammatory markers were determined by enzyme immunoassay. Applied methods of machine learning covered the main group of approaches to supervised learning such as linear models (logistic regression), quadratic discriminant analysis (QDA), support vector machine (linear SVM, RBF SVM), k-nearest neighbors algorithm, Gaussian processes, naive Bayes classifier, decision trees, and ensemble models (AdaBoost, random forest, XGBoost). The importance of features for prediction from the best fold has been analyzed for the machine learning methods, which demonstrated the best quality. The most significant features were selected using 70% quantile threshold.

Results: The AdaBoost ensemble model with ROC AUC of 0.71±0.15 and average accuracy (ACC) of 0.78±0.11 has demonstrated the best quality on a 10-fold cross validation test sample. Within the frameworks of the present investigation, the AdaBoost model has shown a good quality of classification between the patients with schizophrenia and healthy volunteers (ROC AUC over 0.70) at a high stability of the results (σ less than 0.2). The most important immunological parameters have been established for differentiation between the patients and healthy volunteers: the level of some systemic inflammatory markers, activation of humoral immunity, pro-inflammatory cytokines, immunoregulatory cytokines and proteins, Th1 and Th2 immunity cytokines. It was for the first time that the possibility of differentiating schizophrenia patients from healthy volunteers was shown with the accuracy of more than 70% with the help of machine learning using only immune parameters.The results of this investigation confirm a high importance of the immune system in the pathogenesis of schizophrenia.