Martin Reichel1, Stefanie Hönig2, Gerhard Liebisch3, Anja Lüth4, Burkhard Kleuser5, Erich Gulbins6, Gerd Schmitz7, Johannes Kornhuber8. 1. Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. Electronic address: martin.reichel@uk-erlangen.de. 2. Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. Electronic address: stefanie.hoenig@uk-erlangen.de. 3. Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. Electronic address: gerhard.liebisch@klinik.uni-regensburg.de. 4. Institute of Nutritional Sciences, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. Electronic address: anja.Lueth@bfr.bund.de. 5. Institute of Nutritional Sciences, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. Electronic address: burkhard.kleuser@uni-potsdam.de. 6. Department of Molecular Biology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany. Electronic address: erich.gulbins@uni-due.de. 7. Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. Electronic address: gerd.schmitz@klinik.uni-regensburg.de. 8. Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. Electronic address: johannes.kornhuber@uk-erlangen.de.
Abstract
BACKGROUND: Alcohol abuse is a major risk factor for somatic and neuropsychiatric diseases. Despite their potential clinical importance, little is known about the alterations of plasma glycerophospholipid (GPL) and sphingolipid (SPL) species associated with alcohol abuse. METHODS: Plasma GPL and SPL species were quantified using electrospray ionization tandem mass spectrometry in samples from 23 male alcohol-dependent patients before and after detoxification, as well as from 20 healthy male controls. RESULTS: A comparison of alcohol-dependent patients with controls revealed higher phosphatidylcholine (PC; P-value=0.008) and phosphatidylinositol (PI; P-value=0.001) concentrations in patients before detoxification, and higher PI (P-value=0.001) and phosphatidylethanolamine (PE)-based plasmalogen (PE P; P-value=0.003) concentrations after detoxification. Lysophosphatidylcholines (LPC) were increased by acute intoxication (P-value=0.002). Sphingomyelin (SM) concentration increased during detoxification (P-value=0.011). The concentration of SM 23:0 was lower in patients (P-value=2.79×10(-5)), and the concentrations of ceramide Cer d18:1/16:0 and Cer d18:1/18:0 were higher in patients (P-value=2.45×10(-5) and 3.73×10(-5)). Activity of lysosomal acid sphingomyelinase (ASM) in patients correlated positively with the concentrations of eight LPC species, while activity of secreted ASM was inversely correlated with several PE, PI and PC species, and positively correlated with the molar ratio of PC to SM (Pearson's r=-0.432; P-value=0.039). CONCLUSION: Plasma concentrations of numerous GPL and SPL species were altered in alcohol-dependent patients. These molecules might serve as potential biomarkers to improve the diagnosis of patients and to indicate health risks associated with alcohol abuse. Our study further indicates that there are strong interactions between plasma GPL concentrations and SPL metabolism.
BACKGROUND:Alcohol abuse is a major risk factor for somatic and neuropsychiatric diseases. Despite their potential clinical importance, little is known about the alterations of plasma glycerophospholipid (GPL) and sphingolipid (SPL) species associated with alcohol abuse. METHODS: Plasma GPL and SPL species were quantified using electrospray ionization tandem mass spectrometry in samples from 23 male alcohol-dependent patients before and after detoxification, as well as from 20 healthy male controls. RESULTS: A comparison of alcohol-dependent patients with controls revealed higher phosphatidylcholine (PC; P-value=0.008) and phosphatidylinositol (PI; P-value=0.001) concentrations in patients before detoxification, and higher PI (P-value=0.001) and phosphatidylethanolamine (PE)-based plasmalogen (PE P; P-value=0.003) concentrations after detoxification. Lysophosphatidylcholines (LPC) were increased by acute intoxication (P-value=0.002). Sphingomyelin (SM) concentration increased during detoxification (P-value=0.011). The concentration of SM 23:0 was lower in patients (P-value=2.79×10(-5)), and the concentrations of ceramide Cer d18:1/16:0 and Cer d18:1/18:0 were higher in patients (P-value=2.45×10(-5) and 3.73×10(-5)). Activity of lysosomal acid sphingomyelinase (ASM) in patients correlated positively with the concentrations of eight LPC species, while activity of secreted ASM was inversely correlated with several PE, PI and PC species, and positively correlated with the molar ratio of PC to SM (Pearson's r=-0.432; P-value=0.039). CONCLUSION: Plasma concentrations of numerous GPL and SPL species were altered in alcohol-dependent patients. These molecules might serve as potential biomarkers to improve the diagnosis of patients and to indicate health risks associated with alcohol abuse. Our study further indicates that there are strong interactions between plasma GPL concentrations and SPL metabolism.
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