New and Upcoming Markers of Alcohol Consumption

138 Pages·2001·4.34 MB·English

by  Gabi Koller

Friedrich M. Wurst (Ed.) • New and Upcoming Markers of Alcohol Consumption
Friedrich M. Wurst
(Editor)
New and Upcoming
Markers of
Alcohol Consumption
, Springer
Editor
Dr. Friedrich M. Wurst
Psychiatric University Hospital
Wilhelm-Klein-Strasse 27
CH-402S Basel
Switzerland
ISBN-13: 978-3-642-96010-9 e-ISBN-13: 978-3-642-96008-6
001: 10.1007/978-3-642-96008-6
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This book is dedicated
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Preface
New and upcoming markers of alcohol consumption
The abstinence oriented treatment of people with alcohol problems requires efficient
methods for monitoring alcohol abstinence.
It is an important step in clinical and forensic practice to integrate biological state
markers with a reasonable time frame of detection and a high sensivity and specific
ity to control alcohol use in the sense of lapse or relapse.
Friedrich Martin Wurst contributes continuously excellent research data and has mer
itoriously joined the most prominent specialists of all over the world to focus on dif
ferent aspects of alcohol markers. I hope that this book will motivate people in basic
research as well as clinicians to gain more knowledge and develop methods to treat
people with alcohol problems.
Dr. Dieter Ladewig
Professor of Psychiatry and
Addiction Medicine
Department of Psychiatry
University Basel
Basel, November 6th. 2000
Foreword of the editor
Increasingly sophisticated methods to measure health and its burden, in particular the
DALY (Disability Adjusted Life Year), have helped to provide a more balanced con
ception of the needs and priorities in the area of health for both developing and devel
oped countries.
Both in developing countries and in industrialised societies mental problems account
for about 10% of lost healthy years in life. This is twice the number for malignant neo
plasms. Furthermore 5 of the 10 leading causes of disability world-wide (major
depression, schizophrenia, bipolar disorders, alcohol use, obsessive compulsive dis
orders) are mental problems. In 1990 there have been 288 million cases of alcohol
related diseases, which is about 5 times the number of schizophrenia in that year
(http://www.who.int/inf-fs/en/fact217.html).
Therefore, to monitor alcohol consumption in clinical as well as in forensic practice,
occupational medicine, at court and for traffic safety and safety at workplaces biologi
cal state markers of high sensitivity and specificity, capable of monitoring those in treat
ment for alcohol dependence or poly-drug-abusers as well as social drinkers in risky sit
uations (driving, workplaces) are required. They are a necessity e.g. to improve diagno
sis, therapy outcome and quality of life of the patients, increase safety both at workplac
es and in traffic, avoid harm to the unborn during pregnancy (fetal alcohol syndrome),
reduce costs, by making therapy more effective and reduce productivity loss.
Furthermore neuropsychological impairment following alcoholisation, though blood
ethanol concentration is zero, usually referred to as hangover state might playa cru
cial role in accidents.
Numerous tests and devices (including sweat patches and transdermal electronic alco
hol sensors) for different body fluids and tissues have been developed and suggested
to disclose (recent) alcohol consumption.
The known markers, however can not be considered to be satisfying with regard to
sensitivity and specificity. Furthermore, they do not cover the whole time axis for alco
hol intake - i.e. there is a gap with regard to alcohol consumption of between 1 day
and 1-2 weeks, between short - and long-term markers like ethanol, methanol, and
CDT, GGT or MCV respectively. These traditional markers are in many cases besides
alcohol influenced by age, gender and a variety of substances and non-alcohol asso
ciated diseases.
This book, emerging from a symposium at the World Congress of Psychiatry in
Hamburg 1999, in the first chapter gives an overview on both state and trait markers
form a psychiatric perspective, whereas the following chapters highlight some - by far
not all - of the promising newer markers of alcohol consumption.
It is my distinct pleasure to thank the authors for providing the manuscripts and those,
who made the publication possible, namely Organon Germany, Organon Switzerland,
GlaxoSmithKline Switzerland and Steinkopff Verlag.
May this book stimulate research and debate in the field.
Basel, May 2001 Friedrich Martin Wurst
Table of contents
1 Preface
Dieter Ladewig VI
2 Foreword
Friedrich Martin Wurst . VII
3 Biological and genetic markers of alcoholism - a psychiatric perspective
Gabi Koller, Michael Soyka .................... .
4 Possible role of long chain fatty acid ethyl esters in organ injury
and as short-term markers of ethanol intake in humans
Margareta A. Diczfalusy, Mats von Wachenfeldt, Inger Holmberg,
Stefan E. H. Alexson . . . . . . . . . . . . . . . . . . . . . . . . 17
5 Methanol and congeners as markers of alcohol use and abuse
Thomas Gilg . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
6 5-HTOL is a sensitive marker of recent alcohol consumption
Stefan Borg, Olof Beck .................... . 53
7 The direct ethanol metabolite ethyl glucuronide:
A specific marker of recent alcohol consumption
Friedrich Martin Wurst, Joerg Metzger, Katja Jachau, Stephan Seidl,
Lutz Pridzun, Ines Janda, Andreas Alt ............... 62
8 Phosphatidylethanol; clinical significance and biochemical basis
Arthur Varga, Kristian Moller, Per Hansson, Steina Aradottir,
Christer Alling ......................... . 75
9 Proteins modified by direct and indirect ethanol metabolites,
and their associated antibodies, as markers of alcohol intake
Simon Worrall . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
10 Salsolinol - An endogenous neurotoxin in the biology of alcoholism
Frank Musshoff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112
Biological and genetic markers of alcoholism -
a psychiatric perspective
Gabi Koller
Michael Soyka
Ludwig-Maximilians Universitat Munchen
Psychiatric Departement
NuBbaumstraBe 7
80336 Munich
Phone: [phone]
FAX: [phone]
Email: [email protected]
2 Koller G. and Soyka M.
Abstract
With respect to alcoholism the term "marker" often is used misleading. Generally,
state markers of alcoholism must be differentiated from trait markers or markers
of alcohol intoxication. Trait markers are hereditary, time independent factors.
Trait markers persist during the whole time. For alcoholism a number of possible
neurochemical and neurophysiological trait markers including the monoaminoxi
dase-B-activity in platelets, activity of adenylatcyclase, endocrine markers (corti
sol, ACTH, prolactin), dopamin-beta-hydroxylase, evoked potentials (P 300) and
ADHIALDH genotypes have been proposed, but none of these markers has been
fIrmly established. State markers are occuring during the phases of alcohol con
sumption. State markers such as blood alcohol concentration, CDT, GGT, ASAT,
ALAT, MCV, HDL- and VDRL-cholesterol, and others are widely used for dia
gnosis and screening of alcoholics but both sensitivity and specifIty are limited
(Gjerde et aI., 1988). Also except for MCV, pathologic fmdings are bound to a
relatively fast biological turnover and return to normal values in abstinent patients.
Some authors shown association markers for example HLA antigen, blood groups
or transketolase.
Alcohol markers of special relevance for psychiatric diagnosis are reviewed in this
paper.
Biological and genetic markers of alcoholism - a psychiatric perspective 3
Trait Markers
Platelet Adenylyl Cyclase
The activities of some platelet enymes have been proposed to reflect changes of
enzymes found in the brain. The activity of platelet adenylyl cyclase after sti
mualtion with guanine nucleotide, cesium flouride, or prostaglandine E 1 was
reported to be decreased in in alcoholics (Valverius et aI., 1988). This was not
associated with age, race, smoking or illicit drugs and there was no significant
correlation with the duration alcohol intake. Activity was also decreased in alco
holics who abstained from alcohol for one or two years. These results were later
confirmed and at this time no difference was found between typ I and typ II alco
holics (Parsian et aI., 1996). In 1998 marked state dependent changes of lym
phocyte adeny1yl cyclase activities have been demonstrated in alcohol dependents
during detoxification (Pauly et aI., 1999). To date the possible role of a trait mar
ker platelet adenylyl cyclase is not entirely clear.
Platelet Monoamine Oxidase
Platelet monoamine oxidase is a mitochondrial enzyme involved in the breakdown
of neuronal transmitters like noradrenaline, adrenaline, dopamine or serotonine.
Two isoenzymes are known, MAO A and MAO B. Both are found in the central
nervous system. Type A is involved in the metabolism of serotonin and norepi
nephrine and type B degrades phenylethylamine and benzylamine. Only the latter
form can be found in platelets. The genes for MAO-A and MAO-B are located in
the short arm of human X chromosome 8 ( Xp 11.3). Over 50-fold variations of
MAO-A and MAO-B activities have been shown in humans (Murphy et aI., 1979).
Low platelet monoamine oxidase (MAO) activity in human alcoholics as com
pared to controls has been found in many studies (Faraj et aI., 1987), (Wiberg et
aI., 1977). Some studies failed to show this effect (Giller et aI., 1984), (Tabakoff et
aI., 1988). Since alcoholism is a very heterogenous disorder with mUltiple sub
groups more recent studies have tried to link reduced MAO B activity in alcohol
ics with certain personality traits or family history of alcoholism. In some studies a
reduced MAO B activity in alcoholics was associated with type II alcoholism
(Cloninger, 1987), a subtype which associated with high heretability, early age of
onset and severe social and legal consequences of alcoholism (Pandey et aI.,
1988), (von Knorring et aI., 1991), but several studies found no association be
tween reduced MAO B activity and type II alcoholism (Yates et aI., 1990),
(Parsian et aI., 1996). Especially the possible association of reduced platelet MAO
B activity and family history of alcoholism has attracted substantial attention in
recent years. A reduced activity has also been shown in relatives of alcoholics.
(Alexopoulos et aI., 1983; Coursey et aI., 1982; Devor et aI., 1993). Romme1-
spacher et al (1994) found a significantly lower platelet MAO B activity in alco
holics with high novelty-seeking and impulsiveness scores as measured by the
Tridimensional Personality Questionnaire but these findings also need further
confirmation (Rommelspacher et aI., 1994).