Neuronal lipidome in schizophrenia and metabolic syndrome: Potential interventions

Life is dependent on the separation of various body compartments from each other and the environment. The permeability of biological barriers, including the enhanced barriers of the gastrointestinal and blood-brain, depends on the integrity of cell or mitochondrial membranes and intercellular junctions. Severe mental illness and metabolic syndrome are characterized by premature cellular senescence that alters the permeability of biological membranes. Increased barrier permeability enables microbial migration outside the gastrointestinal tract, eventually reaching the brain, skeletal muscles, and adipose tissue. Immune responses to invading micro-organisms or their components likely contribute to dysmetabolism and neuropathology, including schizophrenia. Entropy, a biophysical measure of randomness or disorder, may detect senescence-induced changes early, thus allowing for interventions to avert microbial translocation and the subsequent pathology. The primary objective of this narrative review is to emphasize the role of lipidome pathology as the common denominator in schizophrenia and metabolic syndrome. The secondary objective to emphasize the clinical implications of lipidome replacement. METHODS: Review of the existing literature on membrane lipidome in s schizophrenia and metabolic syndrome published during the past decade. MEDLINE/PubMed databases from 2015 to 2025 were searched, using the words "lipidome in schizophrenia, schizophrenia spectrum disorders (SSDs), and metabolic syndrome". We identified 46 distinct, high-quality, full-text studies. 16 papers, linking membrane-specific lipidomics to this pathology were chosen. RESULTS: Membrane lipidome oxidation alters biological barriers that may result in pathology, including schizophrenia and metabolic syndrome. Conversely, this pathology may be averted or reversed by membrane lipid replacement, plasminogen replacement therapy, gamma wave entrainment and other biophysical modalities.