Abnormal transbilayer distribution of phospholipids in red blood cell membranes in schizophrenia.
Abnormalities in membrane lipids have been repeatedly reported in patients with schizophrenia. These abnormalities include decreased phosphatidylethanolamine (PE) and n-3 and n-6 polyunsaturated fatty acids in peripheral and brain cell membranes. The present study investigates the hypothesis of an overrepresentation of PE in the external leaflet of the red blood cell (RBC) membrane in patients with schizophrenia. The assumption was that this modification of PE asymmetrical distribution could explain the reported lipid membrane abnormalities. Phosphatidylethanolamine located in the external leaflet was specifically labeled in RBC membranes from 65 medicated patients with schizophrenia and 38 healthy controls. Labeled (external) and non-labeled (internal) PE and their respective fatty acid composition were analyzed by mass spectrometry. A significant increase in the percentage of external leaflet PE was found in RBC membranes in 63.1% of the patients. In this subgroup, a significant depletion of n-3 and n-6 polyunsaturated fatty acids from internally located PE was also observed. Age, sex and antipsychotic treatment were not associated with the transbilayer membrane distribution of PE. Potential mechanisms underlying these abnormalities may involve membrane phospholipid transporters or degradative enzymes involved in phospholipid metabolism. The anomaly described could characterize a subgroup among patients with schizophrenia.
Nuss
Philippe
P
UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012 Paris, France. philippe.nuss@sat.aphp.fr
Tessier
Cedric
C
Ferreri
Florian
F
De Hert
Marc
M
Peuskens
Joseph
J
Trugnan
Germain
G
Masliah
Joelle
J
Wolf
Claude
C
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008875:Middle Aged; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
D014150:Antipsychotic Agents; D005227:Fatty Acids; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C483858:phosphatidylethanolamine