Abstract
Schizophrenia is a severe mental condition in which several lipid abnormalities—either structural or metabolic—have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM−) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM− patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.
Highlights
Schizophrenia is a chronic multifactorial disorder characterized by a number of symptom dimensions, cognitive abnormalities and functional impairment
11 Jensen JE, Miller J, Williamson PC, Neufeld RW, Menon RS, Malla A et al Grey and CONCLUSION We found evidence that a specific red blood cell (RBC) membrane lipid cluster was associated with differences in dopamine-related clinical and cognitive manifestations in schizophrenia patients
12 Nuss P, Tessier C, Ferreri F, De Hert M, Peuskens J, Trugnan G et al Abnormal transbilayer distribution of phospholipids in red blood cell membranes in schistudied clinical or treatment variables could account for these zophrenia
Summary
Schizophrenia is a chronic multifactorial disorder characterized by a number of symptom dimensions, cognitive abnormalities and functional impairment. These features are highly variable among individuals with schizophrenia, resulting in great heterogeneity in clinical presentation. Lipids are understood as versatile and dynamic regulators of numerous cellular processes that encompass, among others, signaling, budding and fusion of vesicles.[2] Lipids are known to move rapidly in the plane as well as across the bilayer in a dynamic and highly organized manner, in red blood cell (RBC),[3] to control various cellular activities.[4] In this context, the lipid pattern abnormality in membranes is conceived as a trait or vulnerability marker associated with the disorder. Brain signaling may be assessed indirectly via the study of the lipid composition of membrane in peripheral cells such as RBCs.[6,7,8]
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