Comparative lipidomic alterations in the anterior cingulate cortex in schizophrenia and major depression

Schizophrenia and major depressive disorder are typically classified as distinct psychiatric conditions; however, they share overlapping symptoms and biological risk factors. Identifying molecular features that distinguish or unify these disorders may provide insights into their underlying mechanisms. Lipid metabolism is increasingly recognized as an important factor influencing brain function and the development of mental disorders, yet direct comparative lipidomic analyses of these two conditions remain limited. In this study, we examined the lipidomic profiles of the anterior cingulate cortex (ACC), a region central to emotional regulation and cognitive control, across schizophrenia, major depression and control cohorts. Both disorders showed increased levels of free fatty acids (FA) and lysophosphatidylcholines (LPC). Additionally, major depression was characterized by alterations in glycerolipid classes, whereas schizophrenia exhibited decreased levels of acylcarnitines (CAR). This pattern was further confirmed by targeted analysis of carnitine metabolites. Our results suggest that abnormalities in brain lipid metabolism, particularly in pathways related to cellular energy regulation and glycerolipid remodeling, differ between schizophrenia and depression, providing potential markers to distinguish these disorders and clarify their biological characteristics.