Omics-based immune profile in first-episode psychosis : revealing biomarkers for understanding schizophrenia pathophysiology

Abstract

Schizophrenia is a lifelong, severe mental health disorder characterized by significant disability, disrupted psychosocial functioning, and premature mortality. Typically emerging in early adolescence, schizophrenia imposes a substantial healthcare burden worldwide. This thesis provides a comprehensive examination of fluid biomarkers and metabolic pathways during the onset and progression of psychosis, with a particular focus on first-episode psychosis (FEP).

The pathophysiology of schizophrenia is linked to neurotransmitter activities such as dopamine, glutamate, and γ-aminobutyric acid, giving rise to several theories including those of dopamine, glutamate, kynurenic acid, and neuroinflammation. There is an urgent need to identify new drug targets to develop more effective medications that goes beyond symptomatic management of psychosis, emphasizing the limitations in current treatments. Omics studies, including proteomics and metabolomics, could revolutionize schizophrenia treatment by offering a more systematic approach to identifying drug response markers and minimizing adverse effects in therapies. Through metabolomics and proteomics analyses of cerebrospinal fluid (CSF) and serum metabolites, this research identifies crucial alterations that indicates the potential of these biomarkers in diagnosing and monitoring schizophrenia and related disorders. Collectively, these studies deepen our understanding of the biological underpinnings of psychosis and support the development of biomarker-based diagnostic and therapeutic strategies. This research highlights the intricacy of schizophrenia, which involves a complex interplay of metabolic, genetic, and inflammatory factors.