Proteomic profiling in psychiatric disorders and COVID-19

Abstract

This thesis presents an integrative proteomic profiling study investigating schizophrenia, depression and COVID-19, with the goal of identifying peripheral biomarkers that can aid diagnosis and guide treatment selection. Mental health disorders represent a major global health burden, with depression and schizophrenia among the leading causes of disability worldwide. The COVID-19 pandemic has further exacerbated this crisis, increasing the prevalence and severity of depressive and anxiety symptoms across populations, while also worsening outcomes for individuals with pre-existing psychiatric conditions. Understanding the biological underpinnings of these disorders is therefore critical for improving early detection and personalised care.

Proteomic analysis using Olink technology was conducted on plasma samples from clinically well-characterised cohorts of patients with schizophrenia, depression and COVID-19, alongside matched healthy controls. In schizophrenia, dysregulation of proteins including CCL11, MMP9 and IGFBP1 indicated chronic inflammation, blood-brain barrier disruption and metabolic imbalance. Depression was marked by altered expression of IL-6, IL-1β, IGFBP2 and leptin, reflecting overlapping inflammatory, hormonal and neurovascular disturbances. COVID-19-associated psychological distress signatures highlighted variable immune states, with IL-7 and CCL17 indicating chronic inflammation and increased IFNG linked to reduced serotonin.

Machine-learning models integrating proteomic features achieved high accuracy in classifying patients versus controls and differentiating between diagnostic groups across cohorts. From these analyses, distinct panels of biomarkers were proposed for each condition, combining immune mediators (e.g., CCL7, TNFRSF10A), metabolic regulators (e.g., IGFBP4, LEP) and neurotrophic or structural factors (e.g., GDNFRα3, PLAUR). Drug repurposing analysis also revealed novel therapeutics not previously studied in psychiatric populations, offering targeted strategies to modulate these molecular signatures.

Overall, this thesis advances the application of proteomics in psychiatry and infectious disease by uncovering biomarker signatures that bridge molecular pathology and clinical presentation. These findings support the development of blood-based diagnostic tools and personalised treatment strategies, moving toward precision medicine approaches in mental health and COVID-19 care.

Thesis is embargoed until 31st May 2028

Date of Award	May 2026
Original language	English
Sponsors	Department of Education (Northern Ireland)
Supervisor	Elaine Murray (Supervisor), Margaret McLafferty (Supervisor) & Sarah Atkinson (Supervisor)