Citation: Ponizovsky AM, Barshtein G, Nechamkin Y, Lecht S, Bergelson LD. Differences in the Lipid Domain Organization of Erythrocyte Membranes in Patients with Schizophrenia. J Neurol Psychol. 2015;3(1): 6. J Neurol Psychol January 2015 Vol.:3, Issue:1 © All rights are reserved by Ponizovsky et al. Differences in the Lipid Domain Organization of Erythrocyte Membranes in Patients with Schizophrenia Ke ywords: Erythro c yte me mb ra ne ; Lip id d o ma ins; Fluo re sc e nc e me a sure me nts; Sc hizo p hre nia ; Symp to ma to lo g y Abstra c t G ra d ua lly a c c umula ting e vid e nc e ind ic a te s tha t sc hizo p hre nia ma y b e a c c o mp a nie d b y a lte ra tio ns o f me mb ra ne p ho sp ho lip id s, ho we ve r kno wle d g e a b o ut ho w it a ffe c ts lip id d o ma in o rg a niza tio n of membrane is lacking. We compared the membrane lipid domain o rg a niza tio n o f re d b lo o d c e ll (RBC ) me mb ra ne s fro m two g ro up s o f p a tie nts with sc hizo p hre nia se le c te d b y the ir hig h p o sitive synd ro me (PS) o r ne g a tive synd ro me (NS) sc o re s o n the Po sitive a nd Ne g a tive Synd ro me Sc a le , a nd c o ntro l sub je c ts witho ut kno wn p syc hia tric histo ry. Diffe re nc e s in the surfa c e d istrib utio n o f the me mb ra ne p ho sp ho lip id s were elucidated by: 1) registering the luorescence excitation spectra o f the p o la rity-se nsitive lip id p ro b e La urd a n inc o rp o ra te d into the RBC me mb ra ne , 2) me a suring the re so na nc e e ne rg y tra nsfe r (RET) fro m tryptophan to luorescent analogs of the main RBC phospholipids p ho sp ha tid ylc ho line a nd sp hing o mye lin, a nd 3) d e te rmining the c ha ng e s in RET fro m tryp to p ha n to the sp hing o mye lin p ro b e ind uc e d b y p ro sta g la nd in E1. The d a ta o b ta ine d with RBC s fro m e ithe r no rma l subjects or PS patients were largely similar, but differed signiicantly fro m tho se o b ta ine d with RBC s o f p a tie nts with NS sc hizo p hre nia . The re sults sup p o rt va lid ity o f the c linic a l d istinc tio n o f sc hizo p hre nia into p o sitive a nd ne g a tive sub typ e s. Introduction Most approaches to subtyping schizophrenia have made use of the concept of positive and negative syndromes (PS and NS). PS are characterized by hallucinations, delusions and thought disorders whereas apathy, emotional blunting and psychomotor retardation are regarded as NS [1]. Although the positive-negative dichotomy is believed by some authors to be a simpliication [2-4], it has important clinical and prognostic signiicance. A number of recent investigations have revealed that the positive and negative syndromes are associated with diferent biochemical changes. Particularly, previous studies have detected certain speciic lipid aberrations in red blood cells (RBC) from psychiatric patients with predominantly negative symptoms [5-8]. Recently, we reported on noticeable increases in both the sphingomyelin level and the aggregability of RBCs from patients with schizophrenia with mainly NS in comparison to those from patients with schizophrenia with mainly PS and normal controls [9,10]. Previously, RBCs from patients with schizophrenia were found to be enriched also in cholesterol and glycolipids [11- 13] and their membranes were reported to be less “luid” than those of normal erythrocytes [11,13]. However the concept of membrane luidity depends on the assumption that the hydrophobic region of the membrane is structurally and dynamically homogeneous, whereas in eukaryotic cells including human and rabbit erythrocytes [14-18], the surface lipids appear to distribute unevenly between Alexander M. Ponizovsky 1 *, Gregory Barshtein 2 , Yakov Nechamkin 3 , Shimon Lecht 4 and Lev D. Bergelson 4 1 Research Unit, Mental Health Services, Ministry of Health, Jerusalem, Israel 2 Department of Biochemistry, Hadassah Medical School, The Hebrew University of Jerusalem, Israel 3 Sha’ar Menashe Mental Health Center, Hadera, Israel 4 Biological Membrane Group, School of Pharmacy, the Hebrew University of Jerusalem, Israel *Address for Correspondence Alexander M. Ponizovsky, MD, PhD, Research Unit, Mental Health Services, Ministry of Health, 39 Yirmiyahu St., PO Box 1176, Jerusalem 9446724, Israel, E-mail: alexpon8@gmail.com Submission: 24 November 2014 Accepted: 22 December 2014 Published: 29 December 2014 Research Article Open Access Journal of Neurology and Psychology Avens Publishing Group Invi ting Innovations lateral micro-domains. Since the activity of membrane receptors and membrane bound enzymes depends on the physical state of their nearest environment, local properties pertaining to lipid domains in the immediate neighborhood of membrane proteins may be more relevant than bulk lipid properties. Nevertheless the connection between lipid domain structure and pathophysiological events is a new, still poorly explored ield of clinical biochemistry. In recent years it has been found that in many cells sphingolipids and cholesterol cluster together forming movable domains or rats, which are believed to be involved in signal transduction and cell-cell interactions [19]. In view of the unusually high sphingomyelin (SM) levels in RBC from patients with NS schizophrenia [9] we therefore thought it of interest to obtain more information about the lipid distribution in the RBC membrane, particularly, the lateral segregation of its two main phospholipid species, SM and phosphatidylcholine (PC) in membranes of RBCs isolated from the blood of patients with schizophrenia with deined clinical symptom scale scores. In this study we attempted to detect diferences in the lipid domain structure of erythrocytes from normal subjects and subgroups of patients with patients with PS or NS schizophreniaby studying excitation spectra of the polarity-sensitive luorescent membrane probe Laurdan, as well as by measuring the luorescence resonance energy transfer (RET) from protein tryptophans to luorescent analogs of SM and PC incorporated into the erythrocyte membrane. Some earlier studies of polyunsaturated fatty acids, prostaglandin synthesis and prostaglandin receptor activity suggested a role for prostaglandins in the pathophysiology of schizophrenia (reviewed in [20]). Because red blood cells are known to be extremely sensitive to prostaglandin E 1 (PGE 1 ) [15,21-26] (see also [21,22] for reviews of the older literature), we here use the multilipid probe approach also to detect possible diferences between the response to PGE 1 of the phospholipid domain organization in the membranes of normal red cells and those isolated from the blood of patients with predominantly NS schizophrenia.