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Open AccessArticle

Peripheral Acid Sphingomyelinase Activity Is Associated with Biomarkers and Phenotypes of Alcohol Use and Dependence in Patients and Healthy Controls

1
Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg (FAU), D-91054 Erlangen, Germany
2
Department of Molecular Biology, University of Duisburg-Essen, D-45259 Essen, Germany
3
Department of Surgery, University of Cincinnati, Cincinnati, OH 45267-0558, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(12), 4028; https://doi.org/10.3390/ijms19124028
Received: 8 November 2018 / Revised: 30 November 2018 / Accepted: 4 December 2018 / Published: 13 December 2018
(This article belongs to the Special Issue Molecular Psychiatry)
By catalyzing the hydrolysis of sphingomyelin into ceramide, acid sphingomyelinase (ASM) changes the local composition of the plasma membrane with effects on receptor-mediated signaling. Altered enzyme activities have been noted in common human diseases, including alcohol dependence. However, the underlying mechanisms remain largely unresolved. Blood samples were collected from early-abstinent alcohol-dependent in-patients (n[♂] = 113, n[♀] = 87) and matched healthy controls (n[♂] = 133, n[♀] = 107), and analyzed for routine blood parameters and serum ASM activity. We confirmed increased secretory ASM activities in alcohol-dependent patients compared to healthy control subjects, which decreased slightly during detoxification. ASM activity correlated positively with blood alcohol concentration, withdrawal severity, biomarkers of alcohol dependence (liver enzyme activities of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase; homocysteine, carbohydrate-deficient transferrin; mean corpuscular volume, and creatine kinase). ASM activity correlated negatively with leukocyte and thrombocyte counts. ASM and gamma-glutamyl transferase were also associated in healthy subjects. Most effects were similar for males and females with different strengths. We describe previously unreported associations between ASM activity and markers of liver damage and myelosuppression. Further research should investigate whether this relationship is causal, or whether these parameters are part of a common pathway in order to gain insights into underlying mechanisms and develop clinical applications. View Full-Text
Keywords: acid sphingomyelinase; alcohol dependence; liver enzymes; sphingolipid metabolism; withdrawal acid sphingomyelinase; alcohol dependence; liver enzymes; sphingolipid metabolism; withdrawal
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MDPI and ACS Style

Mühle, C.; Weinland, C.; Gulbins, E.; Lenz, B.; Kornhuber, J. Peripheral Acid Sphingomyelinase Activity Is Associated with Biomarkers and Phenotypes of Alcohol Use and Dependence in Patients and Healthy Controls. Int. J. Mol. Sci. 2018, 19, 4028.

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