title: Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations.
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.
authors.affiliation: INSERM ERL 1157, CHU Saint-Antoine, Paris, France.|Service de psychiatrie et de psychologie médicale, Hôpital Saint-Antoine, AP-HP, UPMC Université Paris 06, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Tessier
authors.affiliation: UPC KU Leuven, Kortenberg, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Sweers
authors.affiliation: Service de psychiatrie et de psychologie médicale, Hôpital Saint-Antoine, AP-HP, UPMC Université Paris 06, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Frajerman
authors.affiliation: Service de psychiatrie et de psychologie médicale, Hôpital Saint-Antoine, AP-HP, UPMC Université Paris 06, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Bergaoui
authors.affiliation: Service de psychiatrie et de psychologie médicale, Hôpital Saint-Antoine, AP-HP, UPMC Université Paris 06, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Ferreri
authors.affiliation: SYLIA-STAT, Bourg-la-Reine, France.
authors.forename: C
authors.initials: C
authors.lastname: Delva
authors.affiliation: Institut Pierre Louis d'épidémiologie et de Santé Publique, UMRS 1136, INSERM, Sorbonne Universités, UPMC Université Paris 06, Paris, France.|Public Health Department, Saint-Antoine Hospital, AP-HP, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Lapidus
authors.affiliation: INSERM ERL 1157, CHU Saint-Antoine, Paris, France.|UMR 7203, Laboratoire des biomolécules, Sorbonne Universités-UPMC Université Paris 06, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Lamaziere
authors.affiliation: UCL Institute of Cognitive Neuroscience, London, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Roiser
authors.affiliation: UPC KU Leuven, Kortenberg, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: De Hert
authors.affiliation: INSERM ERL 1157, CHU Saint-Antoine, Paris, France.|Service de psychiatrie et de psychologie médicale, Hôpital Saint-Antoine, AP-HP, UPMC Université Paris 06, Paris, France.|UMR 7203, Laboratoire des biomolécules, Sorbonne Universités-UPMC Université Paris 06, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Nuss
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D004298:Dopamine / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D008563:Membrane Lipids / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010743:Phospholipids / Q000378:metabolism; D011594:Psychometrics; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D015398:Signal Transduction / Q000502:physiology*; D013109:Sphingomyelins / Q000378:metabolism; D013223:Statistics as Topic; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D005227:Fatty Acids; D008563:Membrane Lipids; D010743:Phospholipids; D013109:Sphingomyelins; D004298:Dopamine