Lipidomics of the brain, retina, and biofluids: from the biological landscape to potential clinical application in schizophrenia

Schizophrenia is a serious neuropsychiatric disorder, yet a clear pathophysiology has not been identified. To date, neither the objective biomarkers for diagnosis nor specific medications for the treatment of schizophrenia are clinically satisfactory. It is well accepted that lipids are essential to maintain the normal structure and function of neurons in the brain and that abnormalities in neuronal lipids are associated with abnormal neurodevelopment in schizophrenia. However, lipids and lipid-like molecules have been largely unexplored in contrast to proteins and their genes in schizophrenia. Compared with the gene- and protein-centric approaches, lipidomics is a recently emerged and rapidly evolving research field with particular importance for the study of neuropsychiatric disorders such as schizophrenia, in which even subtle aberrant alterations in the lipid composition and concentration of the neurons may disrupt brain functioning. In this review, we aimed to highlight the lipidomics of the brain, retina, and biofluids in both human and animal studies, discuss aberrant lipid alterations in correlation with schizophrenia, and propose future directions from the biological landscape towards potential clinical applications in schizophrenia. Recent studies are in support of the concept that aberrations in some lipid species [e.g. phospholipids, polyunsaturated fatty acids (PUFAs)] lead to structural alterations and, in turn, impairments in the biological function of membrane-bound proteins, the disruption of cell signaling molecule accessibility, and the dysfunction of neurotransmitter systems. In addition, abnormal lipidome alterations in biofluids are linked to schizophrenia, and thus they hold promise in the discovery of biomarkers for the diagnosis of schizophrenia.