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

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.

List of scientific papers

I. Shang, Pei, Ada Man-Choi Ho, Maximilian Tufvesson-Alm, Daniel R. Lindberg, Caroline W. Grant, Funda Orhan, Feride Eren, et al. 2022. ‘Identification of Cerebrospinal Fluid and Serum Metabolomic Biomarkers in First Episode Psychosis Patients’. Translational Psychiatry.12 (1): 229. https://doi.org/10.1038/s41398-022- 02000-1.
https://doi.org/10.1038/s41398-022-02000-1

II. Eren, Feride, Lilly Schwieler, Funda Orhan, Anna Malmqvist, Fredrik Piehl, Simon Cervenka, Carl M. Sellgren, Helena Fatouros-Bergman, Göran Engberg, and Sophie Erhardt. 2023. ‘Immunological Protein Profiling of First-Episode Psychosis Patients Identifies CSF and Blood Biomarkers Correlating with Disease Severity’. Brain, Behavior, and Immunity. 111 (July): 376–85. https://doi.org/10.1016/j.bbi.2023.04.020.
https://doi.org/10.1016/j.bbi.2023.04.020

III. Eren, Feride, Lilly Schwieler, Funda Orhan, Anna Malmqvist, Fredrik Piehl, Simon Cervenka, Carl M. Sellgren, Helena Fatouros-Bergman, Göran Engberg, and Sophie Erhardt. 2023. ‘Preanalytic Handling of Clinical Blood Samples in Assessing Immunological Proteins – Role of Storage Duration’. Brain, Behavior, and Immunity. 114 (November): 163–64. https://doi.org/10.1016/j.bbi.2023.08.013.
https://doi.org/10.1016/j.bbi.2023.08.013

IV. Haroon, Humza, Ada Man-Choi Ho, Vinod K. Gupta, Surendra Dasari, Carl M. Sellgren, Simon Cervenka, Göran Engberg, Feride Eren, Sophie Erhardt, Jaeyun Sung, Doo-Sup Choi et al. 2024. ‘Cerebrospinal Fluid Proteomic Signatures Are Associated with Symptom Severity of First-Episode Psychosis’. Journal of Psychiatric Research. February, S0022395624000645. https://doi.org/10.1016/j.jpsychires.2024.02.002.
https://doi.org/10.1016/j.jpsychires.2024.02.002