Association Between Abnormal Plasma Lipid Metabolism and Psychological Characteristics in Adolescents With Major Depressive Disorder

<b>Background:</b> Major depressive disorder (MDD) in adolescents is a significant global public health issue, yet its pathophysiological mechanism remains unclear. Although changes in lipid metabolites have been observed in people with MDD, most relevant studies focus on adults, with limited research on adolescents. Furthermore, little is known about how interactions between metabolites and psychosocial factors contribute to MDD among adolescents. This study aimed to explore the relationship between lipid metabolism and psychological characteristics in adolescents with MDD to provide insights into its biological mechanisms. <b>Methods:</b> A cross-sectional study was conducted on 40 adolescents with MDD patients and 20 healthy controls (HCs). Plasma samples were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for targeted lipidomics. Spearman analysis was employed to examine the correlation between differentially expressed lipids and the psychological characteristics of participants. <b>Results:</b> We identified significant differences in 37 lipid species, including glycerophospholipids (GPs), glycerolipids (GLs), and sphingolipids (SPs), with a specific focus on lysophosphatidylcholine (LPC; 18:0), which demonstrated high diagnostic potential (area under the curve (AUC) = 0.886). Pathway analysis revealed significant disturbances in GP metabolism. Spearman correlation analysis showed that most differential lipid metabolites were negatively correlated with scores of depressive symptoms, childhood maltreatment (CM), extraversion, and neuroticism, while positively correlated with scores of psychoticism and positive coping in adolescents with MDD. <b>Conclusions:</b> The study showed that adolescents with MDD presented a significantly differentiated profile of plasma lipidomics compared to HCs. These findings may contribute to a better understanding of the role of lipid metabolism in adolescent MDD.