SU2. A Paradoxical Superior Cognitive Performance in Healthy Control With a Membrane Lipid Marker of Schizophrenia: The Role of the Compensatory Lipid Composition

Background: Lipid membrane abnormalities have been described in several neuropsychiatric disorder, in particular schizophrenia (SCZ) and autism. A sphingomyelin (SM) decrease in the red blood cell (RBC) membrane of patients with SCZ was shown to be associated with more severe PANSS scores and poorer cognitive performance (Tessier et al, Transl Psychiatry, 2016; 6(10)). The present study aimed at examining the cognitive performance of the healthy control group as a function of the identified membrane SM status. Methods: Cognitive characteristics and membrane lipid composition of chronic medicated SCZ patients (n = 75) have been examined and compared to a healthy control (HC) population (n = 40). WCST scores were calculated in both the SCZ and HC population. RBC membrane phospholipid classes (PL) and their molecular species were identified and measured by using LC-MS/MS method in both patients and HC. Results: A membrane SM decrease is evidenced in 55.4% of the SCZ population but only 22.5% of the HCs. In patients, the SM decrease was associated with poorer cognitive performance with significantly more trials, errors, perseverative responses, perseverative errors, and nonperseverative errors. In contrast, among HC, the membrane SM decrease was associated with significantly better performances for trials, errors, and nonperseverative error. SM decrease in SCZ and HC population differs in terms of the cluster of compensatory membrane lipid composition with significant differences in fatty-acid molecular species in phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). Conclusion: While in SCZ patients a membrane SM decrease is associated with poorer cognitive performances, the opposite is observed in healthy control on mostly the same WCST tasks. Significant differences in some molecular species in PC, PS, and PE contained in the RBC membranes distinguish the 2 SM decreased HC and SCZ subgroups.