Psychiatry Research
Volume 169, Issue 2 , Pages 91-96 , 30 September 2009

Abnormal transbilayer distribution of phospholipids in red blood cell membranes in schizophrenia

  • Philippe Nuss

      Affiliations

    • UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012, Paris, France
    • INSERM, UMR_S 538, 27, rue de Chaligny, 75012, Paris, France
    • AP-HP, Hôpital Saint Antoine, 184, rue du faubourg St Antoine, 75012, Paris, France
    • Corresponding Author InformationCorresponding author. UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012, Paris, France. Tel.: +33 149 282 655; fax: +33 140 011 347.
    • ,
  • Cedric Tessier

      Affiliations

    • UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012, Paris, France
    • INSERM, UMR_S 538, 27, rue de Chaligny, 75012, Paris, France
    • AP-HP, Hôpital Saint Antoine, 184, rue du faubourg St Antoine, 75012, Paris, France
    • ,
  • Florian Ferreri

      Affiliations

    • UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012, Paris, France
    • AP-HP, Hôpital Saint Antoine, 184, rue du faubourg St Antoine, 75012, Paris, France
    • ,
  • Marc De Hert

      Affiliations

    • University Psychiatric Center Katholieke Universiteit Leuven, Campus Kortenberg, Belgium
    • ,
  • Joseph Peuskens

      Affiliations

    • University Psychiatric Center Katholieke Universiteit Leuven, Campus Kortenberg, Belgium
    • ,
  • Germain Trugnan

      Affiliations

    • UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012, Paris, France
    • INSERM, UMR_S 538, 27, rue de Chaligny, 75012, Paris, France
    • AP-HP, Hôpital Saint Antoine, 184, rue du faubourg St Antoine, 75012, Paris, France
    • ,
  • Joelle Masliah

      Affiliations

    • UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012, Paris, France
    • INSERM, UMR_S 538, 27, rue de Chaligny, 75012, Paris, France
    • AP-HP, Hôpital Saint Antoine, 184, rue du faubourg St Antoine, 75012, Paris, France
    • ,
  • Claude Wolf

      Affiliations

    • UPMC Univ Paris 06, UMR_S 538, CHU St Antoine, 27, rue de Chaligny, 75012, Paris, France
    • INSERM, UMR_S 538, 27, rue de Chaligny, 75012, Paris, France
    • AP-HP, Hôpital Saint Antoine, 184, rue du faubourg St Antoine, 75012, Paris, France

Received 28 October 2007 ,Revised 2 January 2009 ,Accepted 5 January 2009.

References 

  1. Arvindakshan M, Sitasawad S, Debsikdar V, Ghate M, Evans D, Horrobin DF, et al. Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients. Biological Psychiatry. 2003;53:56–64
  2. Assies J, Lieverse R, Vreken P, Wanders RJ, Dingemans PM, Linszen DH. Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group. Biological Psychiatry. 2001;49:510–522
  3. Barbosa NR, Junqueira RM, Vallada HP, Gattaz WF. Association between BanI genotype and increased phospholipase A2 activity in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience. 2007;257:340–343
  4. Bevers EM, Comfurius P, Dekkers DW, Zwaal RF. Lipid translocation across the plasma membrane of mammalian cells. Biochimica et Biophysica Acta. 1999;1439:317–330
  5. Bitbol M, Devaux PF. Measurement of outward translocation of phospholipids across human erythrocyte membrane. Proceedings of the National Academy of Sciences of the United States of America. 1988;85:6783–6787
  6. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Canadian Journal of Biochemistry and Physiology. 1959;37:911–917
  7. Chalon S, Delion-Vancassel S, Belzung C, Guilloteau D, Leguisquet AM, Besnard JC, et al. Dietary fish oil affects monoaminergic neurotransmission and behavior in rats. Journal of Nutrition. 1998;128:2512–2519
  8. Chalon S, Vancassel S, Zimmer L, Guilloteau D, Durand G. Polyunsaturated fatty acids and cerebral function: focus on monoaminergic neurotransmission. Lipids. 2001;36:937–944
  9. Daleke DL. Regulation of transbilayer plasma membrane phospholipid asymmetry. Journal of Lipid Research. 2003;44:233–242
  10. De Marchi N, De Petrocellis L, Orlando P, Daniele F, Fezza F, Di Marzo V. Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids in Health and Disease. 2003;2:5
  11. du Bois TM, Deng C, Huang XF. Membrane phospholipid composition, alterations in neurotransmitter systems and schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2005;29:878–888
  12. Farkas E, de Wilde MC, Kiliaan AJ, Meijer J, Keijser JN, Luiten PG. Dietary long chain PUFAs differentially affect hippocampal muscarinic 1 and serotonergic 1A receptors in experimental cerebral hypoperfusion. Brain Research. 2002;954:32–41
  13. Fenton WS, Hibbeln J, Knable M. Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. Biological Psychiatry. 2000;47:8–21
  14. Florin-Christensen J, Suarez CE, Florin-Christensen M, Wainszelbaum M, Brown WC, McElwain TF, et al. A unique phospholipid organization in bovine erythrocyte membranes. Proceedings of the National Academy of Sciences of the United States of America. 2001;98:7736–7741
  15. Fukuzako H, Fukuzako T, Kodama S, Hashiguchi T, Takigawa M, Fujimoto T. Haloperidol improves membrane phospholipid abnormalities in temporal lobes of schizophrenic patients. Neuropsychopharmacology. 1999;21:542–549
  16. Garnier D. EDI2, Eating Disorder Inventory—2. Florida: Psychological Assessment Resources; 1991;
  17. Giuffrida A, Leweke FM, Gerth CW, Schreiber D, Koethe D, Faulhaber J, et al. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology. 2004;29:2108–2114
  18. Guy W. Clinical global impression (CGI) in assessment manual for psychopharmacology. National Institute of Mental Health. 1976;218:22
  19. Horrobin DF. Lipids and schizophrenia. British Journal of Psychiatry. 1999;175:88
  20. Jayakumar PN, Gangadhar BN, Subbakrishna DK, Janakiramaiah N, Srinivas JS, Keshavan MS. Membrane phospholipid abnormalities of basal ganglia in never-treated schizophrenia: a 31P magnetic resonance spectroscopy study. Biological Psychiatry. 2003;54:491–494
  21. Jensen JE, Al-Semaan YM, Williamson PC, Neufeld RW, Menon RS, Schaeffer B, et al. Region-specific changes in phospholipid metabolism in chronic, medicated schizophrenia: (31)P-MRS study at 4.0 Tesla. British Journal of Psychiatry. 2002;180:39–44
  22. Junqueira R, Cordeiro Q, Meira-Lima I, Gattaz WF, Vallada H. Allelic association analysis of phospholipase A2 genes with schizophrenia. Psychiatric Genetics. 2004;14:157–160
  23. Keshavan MS, Mallinger AG, Pettegrew JW, Dippold C. Erythrocyte membrane phospholipids in psychotic patients. Psychiatry Research. 1993;49:89–95
  24. Keshavan MS, Stanley JA, Pettegrew JW. Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings—part II. Biological Psychiatry. 2000;48:369–380
  25. Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP. Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophrenia Research. 2002;58:1–10
  26. Lafourcade M, Elezgarai I, Mato S, Bakiri Y, Grandes P, Manzoni OJ. Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex. PLoS ONE. 2007;2:e709
  27. Lautin A, Cordasco DM, Segarnick DJ, Wood L, Mason MF, Wolkin A, et al. Red cell phospholipids in schizophrenia. Life Sciences. 1982;31:3051–3056
  28. Law MH, Cotton RG, Berger GE. The role of phospholipases A2 in schizophrenia. Molecular Psychiatry. 2006;11:547–556
  29. Levant B, Crane JF, Carlson SE. Sub-chronic antipsychotic drug treatment does not alter brain phospholipid fatty acid composition in rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2006;30:728–732
  30. Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport. 1999;10:1665–1669
  31. Mahadik SP, Mukherjee S, Correnti EE, Kelkar HS, Wakade CG, Costa RM, et al. Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naive patients at the onset of psychosis. Schizophrenia Research. 1994;13:239–247
  32. Maki P, Veijola J, Jones PB, Murray GK, Koponen H, Tienari P, et al. Predictors of schizophrenia—a review. British Medical Bulletin. 2005;73–74:1–15
  33. Marinetti GV, Love R. Differential reaction of cell membrane phospholipids and proteins with chemical probes. Chemistry and Physics of Lipids. 1976;16:239–254
  34. Mato S, Aso E, Castro E, Martin M, Valverde O, Maldonado R, et al. CB(1) knockout mice display impaired functionality of 5-HT(1A) and 5-HT(2A/C) receptors. Journal of Neurochemistry. 2007;103(5):2111–2120
  35. McGlashan TH, Hoffman RE. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Archives of General Psychiatry. 2000;57:637–648
  36. McNamara RK, Jandacek R, Rider T, Tso P, Hahn CG, Richtand NM, et al. Abnormalities in the fatty acid composition of the postmortem orbitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications. Schizophrenia Research. 2007;91:37–50
  37. Morrot G, Herve P, Zachowski A, Fellmann P, Devaux PF. Aminophospholipid translocase of human erythrocytes: phospholipid substrate specificity and effect of cholesterol. Biochemistry. 1989;28:3456–3462
  38. Mueser KT, McGurk SR. Schizophrenia. Lancet. 2004;363:2063–2072
  39. Pomorski T, Holthuis JC, Herrmann A, van Meer G. Tracking down lipid flippases and their biological functions. Journal of Cell Science. 2004;117:805–813
  40. Ponizovsky AM, Modai I, Nechamkin Y, Barshtein G, Ritsner MS, Yedgar S, et al. Phospholipid patterns of erythrocytes in schizophrenia: relationships to symptomatology. Schizophrenia Research. 2001;52:121–126
  41. Reddy R, Keshavan MS. Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2003;69:401–405
  42. Riley B, Kendler KS. Molecular genetic studies of schizophrenia. European Journal of Human Genetics. 2006;14:669–680
  43. Ryazantseva NV, Novitskii VV, Kublinskaya MM. Changes in the lipid phase of erythrocyte membranes in patients with paranoid schizophrenia. Bulletin of Experimental Biology and Medicine. 2002;133:84–86
  44. Schmitt A, Maras A, Petroianu G, Braus DF, Scheuer L, Gattaz WF. Effects of antipsychotic treatment on membrane phospholipid metabolism in schizophrenia. Journal of Neural Transmission. 2001;108:1081–1091
  45. Seigneuret M, Devaux PF. ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proceedings of the National Academy of Sciences of the United States of America. 1984;81:3751–3755
  46. Sengupta N, Datta SC, Sengupta D. Platelet and erythrocyte membrane lipid and phospholipid patterns in different types of mental patients. Biochemical Medicine. 1981;25:267–275
  47. Smesny S, Rosburg T, Klemm S, Riemann S, Baur K, Rudolph N, et al. The influence of age and gender on niacin skin test results — implications for the use as a biochemical marker in schizophrenia. Journal of Psychiatric Research. 2004;38:537–543
  48. Smesny S, Kinder D, Willhardt I, Rosburg T, Lasch J, Berger G, et al. Increased calcium-independent phospholipase A2 activity in first but not in multiepisode chronic schizophrenia. Biological Psychiatry. 2005;57:399–405
  49. Smesny S, Rosburg T, Nenadic I, Fenk KP, Kunstmann S, Rzanny R, et al. Metabolic mapping using 2D (31)P-MR spectroscopy reveals frontal and thalamic metabolic abnormalities in schizophrenia. Neuroimage. 2007;35:729–737
  50. Tessier C, Nuss P, Staneva G, Wolf C. Modification of membrane heterogeneity by antipsychotic drugs: an X-ray diffraction comparative study. Journal of Colloid Interface Science. 2008;320:469–475
  51. Thomas EA, Yao JK. Clozapine specifically alters the arachidonic acid pathway in mice lacking apolipoprotein D. Schizophrenia Research. 2007;89:147–153
  52. Yao JK, van Kammen DP, Moss HB, Sokulski DE. Decreased serotonergic responsivity in platelets of drug-free patients with schizophrenia. Psychiatry Research. 1996;63:123–132
  53. Yao JK, Leonard S, Reddy RD. Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophrenia Research. 2000;42:7–17
  54. Yao J, Stanley JA, Reddy RD, Keshavan MS, Pettegrew JW. Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites. Biological Psychiatry. 2002;52:823–830
  55. Zimmer L, Delion-Vancassel S, Durand G, Guilloteau D, Bodard S, Besnard JC, et al. Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n−3 polyunsaturated fatty acids. Journal of Lipid Research. 2000;41:32–40
  56. Zwaal RF, Comfurius P, Bevers EM. Surface exposure of phosphatidylserine in pathological cells. Cellular aand Molecular Life Sciences. 2005;62:971–988

PII: S0165-1781(09)00021-3

doi: 10.1016/j.psychres.2009.01.009

Psychiatry Research
Volume 169, Issue 2 , Pages 91-96 , 30 September 2009

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