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

Abstract

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.

Crossed Eye/Hand Laterality and Left‐Eyedness Predict a Positive 24‐Month Outcome in Alcohol‐Dependent Patients

“…A role for sex hormone signaling has been discussed in the development of both alcohol dependence (Lenz et al., ) and handedness (Medland et al., ), which might be a possible link between the 2 conditions. Sexual dimorphisms in alcohol dependence have been repeatedly shown in previous investigations (King et al., ; Lenz et al., ; Mosher Ruiz et al., ; Mühle et al., ; Weinland et al., ), and the present data highlight the importance of sex‐specific analyses in epidemiological and neurobiological studies on alcohol dependence.…”

“…From 2013 to 2014, we recruited 200 alcohol‐dependent patients and 240 healthy control subjects (see Table for cohort characteristics). The following articles including data from the NOAH study have been already published: Lenz and colleagues (), Weinland and colleagues (), Braun and colleagues (), Gegenhuber and colleagues (), Weinland and colleagues (), Mühle and colleagues (, ).…”

Sphingomyelinases and Liver Diseases

“…In the case of ASH, ASMase activity and ASMase mRNA levels have been shown to be upregulated in liver biopsies from patients with acute alcoholic hepatitis [51,[82][83][84]. In line with these observations, ASMase activity has been recently linked to biomarkers and alcohol use and abuse phenotypes in patients and healthy controls [85]. On the other hand, the expression and activity of ASMase have been shown to be increased in liver and serum samples from patients with NASH [86,87].…”

Molecular Psychiatry: Trends and Study Examples

“…This Special Issue also includes the study by Mühle and colleagues [11], which investigated another type of peripheral biomarkers in alcohol-dependent patients: the acid sphingomyelinase, an enzyme that breaks sphingomyelin into ceramide and thereby changes the composition of plasma membranes. As hypothesized, the authors found clinically relevant changes in the enzyme levels in patients, which also correlated with several other biochemical markers of dependence and health.…”