Current State of Fluid Lipid Biomarkers for Personalized Diagnostics and Therapeutics in Schizophrenia Spectrum Disorders and Related Psychoses: A Narrative Review

Schizophrenia spectrum disorders (SSD) are traditionally diagnosed and categorized through clinical assessment, owing to their complex heterogeneity and an insufficient understanding of their underlying pathology. However, disease progression and accurate clinical diagnosis become problematic when differentiating shared aspects amongst mental health conditions. Hence, there is a need for widely accessible biomarkers to identify and track the neurobiological and pathophysiological development of mental health conditions, including SSD. High-throughput omics applications involving the use of liquid chromatography-mass spectrometry (LC-MS) are driving a surge in biological data generation, providing systems-level insight into physiological and pathogenic conditions. Lipidomics is an emerging subset of metabolomics, largely underexplored amongst the omics systems. Lipid profiles in the brain are highly enriched with well-established functions, including maintenance, support, and signal transduction of neuronal signaling pathways, making them a prospective and exciting source of biological material for neuropsychiatric research. Importantly, changes in the lipid composition of the brain appear to extend into the periphery, as there is evidence that circulating lipid alterations correlate with alterations of psychiatric condition(s). The relative accessibility of fluid lipids offers a unique source to acquire a lipidomic "footprint" of molecular changes, which may support reliable diagnostics even at early disease stages, prediction of treatment response and monitoring of treatment success (theranostics). Here, we summarize the latest fluid lipidomics discoveries in SSD-related research, examining the latest strategies to integrate information into multi-systems overviews that generate new perspectives of SSD-related psychosis identification, development, and treatment.