Impaired Membrane Lipid Homeostasis in Schizophrenia

Background and Hypothesis Multiple lines of clinical, biochemical, and genetic evidence suggest that disturbances of membrane lipids and their metabolism are probably involved in the etiology of schizophrenia (SCZ). Lipids in the membrane are essential to neural development and brain function, however, their role in SCZ remains largely unexplored. Study Design Here we investigated the lipidome of the erythrocyte membrane of 80 patients with SCZ and 40 healthy controls using ultra-performance liquid chromatography-mass spectrometry. Based on the membrane lipids profiling, we explored the potential mechanism of membrane phospholipids metabolism. Study Results By comparing 812 quantified lipids, we found that in SCZ, membrane phosphatidylcholines and phosphatidylethanolamines, especially the plasmalogen, were significantly decreased. In addition, the total polyunsaturated fatty acids (PUFAs) in the membrane of SCZ were significantly reduced, resulting in a decrease in membrane fluidity. The accumulation of membrane oxidized lipids and the level of peripheral lipid peroxides increased, suggesting an elevated level of oxidative stress in SCZ. Further study of membrane-phospholipid-remodeling genes showed that activation of PLA2s and LPCATs expression in patients, supporting the imbalance of unsaturated and saturated fatty acyl remodeling in phospholipids of SCZ patients. Conclusions Our results suggest that the mechanism of impaired membrane lipid homeostasis is related to the activated phospholipid remodeling caused by excessive oxidative stress in SCZ. Disordered membrane lipids found in this study may reflect the membrane dysfunction in the central nervous system and impact neurotransmitter transmission in patients with SCZ, providing new evidence for the membrane lipids hypothesis of SCZ.

Automated summary

This study investigated the lipidome of the erythrocyte membrane in patients with schizophrenia (SCZ) and found disturbances in the metabolism of membrane phospholipids. The results showed that phosphatidylcholines and phosphatidylethanolamines were significantly decreased in the membrane of SCZ patients, as well as the total polyunsaturated fatty acids (PUFAs), leading to a decrease in membrane fluidity. Moreover, the accumulation of oxidized lipids and the increase in peripheral lipid peroxides suggested an elevated level of oxidative stress in SCZ. Further exploration revealed the imbalanced unsaturated and saturated fatty acyl remodeling in phospholipids of SCZ patients.