Commentary on the Paper of Thompson P. et al.: Phosphatidylethanol in Postmortem Brain and Serum Ethanol at Time of Death.

THE PAPER OF Thompson and colleagues (2016) contributes from both a scientific and a clinical point of view to a timely and relevant issue, namely the potential role of the ethanol (EtOH) metabolite phosphatidylethanol (PEth) as a biomarker for assessing EtOH intake in autopsy cases. To facilitate early diagnosis and therapy of alcohol-related disorders and thus prevent secondary complications, questionnaires like the Alcohol Use Disorders Identification Test (AUDIT) (Saunders et al., 1993) together with reliable and valid biomarkers are useful. Clearly, biomarkers have the advantage to indicate and reflect alcohol intake, independent of recall bias of the interviewed subjects. Among biomarkers of EtOH intake, EtOH metabolites such as ethyl glucuronide (EtG) and, more recently, PEth have been investigated. PEth is now recommended by the German evidenceand consensus-based guideline on alcohol use disorders (AUD) for screening chronic alcohol intake at the highest level of evidence (level 1) in all settings for assessing drinking habits (Mann et al., 2015; Weinmann et al., 2016). PEth has been employed in settings such as the assessment of driving ability, in forensic psychiatry, in monitoring programs, and for identifying alcohol intake in specific risk groups, for example, for neonatal screening of prenatal alcohol exposure (for review, seeWurst et al., 2015). It should be noted that PEth is not a single molecule but a family of phospholipids with different fatty acids at the sn-1 and sn-2 positions (Gnann et al., 2010). Nutrition can influence the lipids available to be transformed into PEth homologues and thus mediate the substitution of different fatty acids. Liquid chromatography tandem mass spectrometry (LCMS/MS) allows PEth to be detected in blood after a single drinking episode, while multiple drinking on 5 subsequent days leads to the accumulation of PEth in blood (Gnann et al., 2012). In volunteers, a single drinking episode to a blood alcohol concentration (BAC) of 1.0 g/kg (approx. 0.1 g/dl) resulted in a detection window of 3 to 12 days (Schr€ ock et al., 2017). During abstinence, the ratios of different PEth homologues change due to their differing elimination times (Gnann et al., 2014). As PEth seems to be formed as long as alcohol is present in the blood, and higher BAC levels lead to a higher formation rate, the manner of drinking (speed, frequency, single-drinking amounts) and the BAC reached per drinking event may play roles in PEth production. However, this has not yet been investigated in detail. No paper has so far looked at PEth degradation in vivo, nor its mechanism of degradation and which products are formed. Apart from phospholipase D (PL D) activity, PL A1, PL A2, PL B, and PL C can also lead to different forms of “lyso”-PEth, which are currently not detected by LC-MS/ MS methods. A variety of possibilities might explain interindividual differences in the formation of certain PEth homologues. The investigated samples were autopsy cases from a brain bank with death by suicide or from natural causes. To establish a diagnosis, the Mini-International Neuropsychiatric Interview (M.I.N.I.) with DSM-IV (American Psychiatric Association, 1994) criteria were employed. Of note, a differentiation between a lifetime and a current diagnosis of AUD was not possible with the given information. This would have been of interest for data interpretation. In addition to this excellent diagnostic tool, it would be beneficial in future studies to have information about EtOH intake over the days, weeks, and months prior to death. Such information could have been provided by the AUDIT or by timeline follow back, as used for many other studies with living persons. The study is based on PEth concentrations, serum blood levels, and coroner’s reports, reports from next of a kin, on the manner of death and circumstances with the differentiation of suicide and death from natural causes, with a relatively small number of autopsy samples, and thus should be regarded as a pilot study. The samples used were classified into 3 groups: AUD-W (with positive serum EtOH levels present at the time of autopsy), AUD-WO (without positive serum EtOH levels), and controls. As the control group was positive for PEth, it From the Institute of Forensic Medicine (WW, AS), University of Bern, Bern, Switzerland; Institute of Forensic Medicine (AS), Kantonsspital Aarau, Aarau, Switzerland; Paracelsus Medical University (FMW), Salzburg, Austria; University of Basel (FMW), Basel, Switzerland; and Center for Interdisciplinary Addiction Research (FMW), University of Hamburg, Hamburg, Germany. Received for publication November 24, 2016; accepted December 19, 2016. Reprint requests: Friedrich M. Wurst, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria; E-mail: frieder.wurst@gmx.de Copyright© 2017 by the Research Society on Alcoholism.