Predicting antipsychotic responsiveness using a machine learning classifier trained on plasma levels of inflammatory markers in schizophrenia

Author:

Lee Jimmy1ORCID,Yee Jie Yin,Phua Ser-Xian,See Yuen Mei,Andiappan Anand2ORCID,Goh Wilson3

Affiliation:

1. Institute of Mental Health

2. Singapore Immunology Network (SIgN)

3. Nanyang Technological University

Abstract

Abstract

Background In this research study, we apply machine learning techniques to navigate the multifaceted landscape of schizophrenia. Our method entails the development of predictive models, emphasizing peripheral inflammatory biomarkers, which are classified into treatment response subgroups: antipsychotic-responsive, clozapine-responsive, and clozapine-resistant. Methods The study comprises 146 schizophrenia patients (49 antipsychotics-responsive, 68 clozapine-responsive, 29 clozapine-resistant) and 49 healthy controls. Protein levels of immune biomarkers were quantified using the Olink Target 96 Inflammation Panel. To predict labels, a support vector machine classifier is trained on the Olink data matrix and evaluated via leave-one-out cross-validation. Associated protein biomarkers are identified via recursive feature elimination. Findings We constructed three separate predictive models for binary classification: one to discern healthy controls from individuals with schizophrenia (AUC = 0.74), another to differentiate individuals who were responsive to antipsychotics (AUC = 0.88), and a third to distinguish treatment-resistant individuals (AUC = 0.78). Employing machine learning techniques, we identified features capable of distinguishing between treatment response subgroups. Interpretation In this study, support vector machine demonstrates the power of machine learning to uncover subtle signals often overlooked by traditional statistics. Unlike t-tests, it handles multiple features simultaneously, capturing complex data relationships. Chosen for simplicity, robustness, and reliance on strong feature sets, its integration with artificial intelligence techniques like SHapely Additive exPlanations enhances model interpretability, especially for biomarker screening. This study highlights the potential of integrating machine learning techniques in clinical practice. Not only does it deepen our understanding of schizophrenia's heterogeneity, but it also holds promise for enhancing predictive accuracy, thereby facilitating more targeted and effective interventions in the treatment of this complex mental health disorder.

Publisher

Springer Science and Business Media LLC

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