Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

• Published in: PloS one Vol. 8; no. 7; p. e68717
• Main Authors: McEvoy, Joseph, Baillie, Rebecca A., Zhu, Hongjie, Buckley, Peter, Keshavan, Matcheri S., Nasrallah, Henry A., Dougherty, George G., Yao, Jeffrey K., Kaddurah-Daouk, Rima
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.07.2013; Public Library of Science (PLoS)
• Subjects: Aberration; Adult; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Antipsychotics; Aripiprazole; Behavioral sciences; Biomarkers; Brain; Comparative analysis; Control; Development and progression; Diabetes; Diagnostic systems; Disease control; Dopamine; Drugs; Fatty acids; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Omega-6 - metabolism; Fatty Acids, Unsaturated - metabolism; Female; Genetic aspects; Glycerylphosphorylcholine - metabolism; Humans; Iron; Laboratories; Lecithin; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Male; Medical treatment; Mental disorders; Metabolism; Metabolites; Middle Aged; Neurosciences; Patients; Phosphatidylcholine; Phosphatidylethanolamine; Phosphatidylethanolamines - metabolism; Phospholipids; Phospholipids - metabolism; Physiological aspects; Polyunsaturated fatty acids; Psychiatry; Psychosis; Psychotropic drugs; Risperidone; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - metabolism; Serotonin; Studies; United States; North Carolina; Pittsburgh Pennsylvania; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068717

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.