Alcohol use Disorders
4.2.2.1 Aetiology of alcohol problems
Juan C. Negrete
Kathryn J. Gill
Introduction
Approximately 8 out of every 10 persons living in Europe and the Americas would report consuming alcoholic beverages in their lifetime,(1) and the norm is for drinking to start in adolescence: in 2003 the average age of first drink in the United States was 14 years old.(2) Also in the year 2003, 79.3 per cent of persons aged 15 years or more in Canada reported to be current users of alcohol, and 22.6 per cent admitted to having exceeded the country’s safe drinking guidelines (i.e. no more than 14 units/week for males and 12 units/week for females). The same survey elicited a rate of ‘hazardous drinkers’ of 13.6 per cent, defined as all respondents who scored 8+ on the AUDIT screening questionnaire.(3)
Epidemiological data in the United States indicates that roughly one in seven persons who start drinking will develop an alcohol dependence disorder in the course of their lives.(4) The figure is higher among men when compared to women. Of course it is also higher if other clinical forms of alcohol misuse (i.e. alcohol abuse/harmful drinking) are included in the rates in addition to dependence.
A moderate level of alcohol use appears to be relatively harmless; and there exist public health guidelines on ‘safe’ drinking practices. The recommendations vary considerably from country to country, but they all assume a greater vulnerability to alcohol effects in the female gender. In the United Kingdom, for instance, hazardous drinking is thought to start at 21 units/week for men and 16 units/ week for women;(5) and in the United States the equivalent guidelines are 14 and 7 drinks per week.(6) It is among alcohol users who exceed such guidelines that the prevalence of dependence is the highest; up to 40 per cent of the more frequent violators.(7)
The expression ‘alcohol problems’ encompasses a wide range of untoward occurrences, from maladaptive, impaired, or harmful behaviour, to health complications and the condition of alcohol dependence. Alcohol problems are not incurred just by chronic excessive drinkers, but also by persons who drink heavily on isolated occasions (e.g. accidents, violence, poisoning, etc.). Given their
high frequency and social costs, these consequences of acute inebriation represent the most significant public health burden of drinking.(8) This section focuses rather on the causes of problems of a clinical nature, the ones presented by individuals who engage in patterns of repeated excessive drinking, i.e. ‘alcohol dependence’ and ‘alcohol abuse’ (DSM-IV nomenclature) or ‘harmful drinking’ (ICD-10 nomenclature).
high frequency and social costs, these consequences of acute inebriation represent the most significant public health burden of drinking.(8) This section focuses rather on the causes of problems of a clinical nature, the ones presented by individuals who engage in patterns of repeated excessive drinking, i.e. ‘alcohol dependence’ and ‘alcohol abuse’ (DSM-IV nomenclature) or ‘harmful drinking’ (ICD-10 nomenclature).
The causality of alcohol misuse
Alcoholism is a bio-psychosocial phenomenon par excellence; it results from the contribution of multiple individual and environmental risk factors. The complex dynamics influencing its development have been well acknowledged in the literature. Theories have taken many disparate facts into consideration, from the effects of alcohol policy to the influence of familial and sociocultural environments across cultures and over time. Some ethnic groups, for instance, have traditionally had low rates of alcoholism (Asians, Jews, and some North American Aboriginals) and the prevalence is generally higher in males across both age cohorts and ethnicities. Another layer of complexity lies in the fact that alcoholism is a clinically heterogeneous disorder with variable age of onset, drinking patterns, severity, and comorbidity with other mental disorders. In general, alcoholics have one or more clinical diagnoses in addition to alcohol dependence, including drug abuse, antisocial personality disorder, anxiety, and depression. The course of the disorder is variable with high rates of remission and relapse; its manifestation changing in pattern and severity in response to life events (stressors) and other aspects of the environment. A summary of the etiological factors that have been shown to influence the development of alcoholism is shown in Box 4.2.2.1.1.
Sociocultural factors
Macrocultural influences such as values, beliefs, and mores; social role functions; local economy; customs and dietary habits; rapid social change; and cultural stress do shape and dictate the way alcohol is used in human societies. But even within a single society, there is variance in the alcohol problems profile of different subgroups. For instance, drinking, heavy drinking, alcohol use disorders, and treatment for alcoholism are more frequently recorded in men than women,(1) the risk of hospital admission for alcoholic psychosis, acute intoxication, and liver cirrhosis is elevated in unskilled and blue-collar workers when compared with higher occupational categories; alcoholics are over-represented in occupations with flexible work schedules, in those less supervised, and in the ones which facilitate access to alcohol,(9,10) and although there are a larger proportion of regular alcohol users among the older, the wealthier, and the better educated, frequency of heavy drinking (i.e. episodes of intoxication, 5+ drinks at a time) is inversely correlated with age, income, and level of education.(3)
Cultural beliefs about drinking and related social norms largely determine the manner in which alcohol is used. Disorderly conduct and drunken violence are more likely to occur in societies which, while allowing drinking, do view alcohol as an evil substance. Similar consequences can be expected if drunkenness is culturally considered as a ‘time out’, when socially unacceptable behaviours are tolerated or excused.(11) In fact, the social condoning of drunkenness is considered as an epidemiological risk factor. The availability of alcohol and the social promotion of frequent or heavy drinking are examples of social risk. But environmental facilitation per se does not explain the genesis of an alcohol dependence disorder in specific individuals. This disorder is best understood as the result of social prompting and individual vulnerabilities.
Box 4.2.2.1.1 A bio-psychosocial model of the aetiology of alcoholism
The comunity/sociocultural environment
policies affecting availability and price (temperance, prohibition, taxation)
cultural patterns of consumption, social acceptability of drinking/drunkenness
availability of other reinforcers (sources of pleasure/recreation)
employment and/or educational opportunities (anomie/ marginalization)
peer influences/role models (affiliation with deviant subculture)
The family environment
marital breakdown (lower socio-economic status, poor parental monitoring)
family attitudes (availability of drugs/alcohol, modelling of siblings/parents)
intrauterine exposure to alcohol/drugs (potential effects of alcohol, nicotine and other drugs on behaviour and cognition)
familial substance abuse (poverty, violence, and increased rates of early life trauma including neglect and physical/sexual abuse)
Individual/host factors
heritable genetic factors (genetic loading for alcohol/drug dependence, depression, anxiety disorders in first-degree relatives)
differences in response to alcohol (low sensitivity in terms of physiological responses and subjective effects)
metabolic differences (thiamine deficiency, alcohol metabolizing enzymes)
high risk taking behaviours (male sex)
childhood psychopathology (conduct disorder, untreated ADHD)
psychiatric disorders (bipolar, depression, anxiety, schizophrenia)
Psychological factors
Alcoholics do not present a homogeneous premorbid personality profile. However, some distinctive trait clusters have been identified which seem to characterize different types of alcoholics.(12) One such group (type 1) tend to score low in novelty seeking and high in harm avoidance and reward dependence. Another group (type 2) is formed by the natural thrill seekers, who appear to ignore harmful consequences and punitive responses. This latter cluster, which prevails mostly in males with early-onset alcoholism,
is also typical of antisocial personalities. Of all personality features, conduct disorder and antisocial behaviour are the strongest predictors of alcohol misuse.(13)
is also typical of antisocial personalities. Of all personality features, conduct disorder and antisocial behaviour are the strongest predictors of alcohol misuse.(13)
(a) Psychodynamic processes
Early psychodynamic writings portrayed alcoholism and other addictions as regressive behaviours caused by unconscious conflicts over libidinal pleasures, homosexuality, and aggression. More recent formulations emphasize ego and self-developmental problems, and consider psychoactive substance abuse as a response to psychological suffering; an attempt at re-establishing homeostasis. This is known as the self-medication hypothesis of addictions,(14) according to which, persons with self-regulatory deficiencies in the areas of self-care, self-esteem, self-object relations, and affect tolerance, would drink to palliate their distress.
(b) Learning
Alcohol abuse as seen by some as a behavioural pattern which has been learned through mechanisms of classical (i.e. Pavlovian) and operant conditioning. According to this interpretation, the perpetuation of heavy drinking results from its association with conditioned stimuli (cues), and from the action of positive (pleasant effects) or negative (stress reduction) behavioural reinforcement. Additional components of this equation are the so-called alcohol ‘expectancies’. Alcohol abusers tend to overemphasize the pleasant aspects of drinking and to ignore the negative ones; the learning theory of alcoholism assumes that such a cognitive set is also acquired through social exposure. The Social Learning Theory posits that the positive expectancy of relaxation following a drink can facilitate more frequent alcohol use and thus contribute to the development of dependence.(15)
(c) Psychiatric comorbidity
Community and clinical epidemiology findings point to the presence of other psychiatric disorders as one of the most significant psychological risk factors in alcoholism.(16) The co-occurrence is sometimes sequential, with the psychiatric disorder preceding alcoholism; in which case a causal role in the development of heavy/frequent drinking is attributed to the former. While this is often observed in cases of conduct disorder, social phobia, attention deficit-hyperactivity (untreated) and depression, there are other psychiatric disturbances such as panic disorder, generalized anxiety and dysthymia that often become clinically significant only after the person has been abusing alcohol for sometime. These alcohol-induced mood and anxiety disorders represent a sizeable proportion of the comorbidity rates.(17) Whether or not it is ‘primary’, psychological stress is a widely recognized factor in alcoholism treatment failure and relapse.
Yet the comorbidity of some psychiatric disorders (e.g. bipolar disorder, schizophrenia) and alcoholism appears to develop in no predictable sequence, so that if not random, their co-occurrence could be assumed to result from common genetic influences (see below) and pathophysiological mechanisms. One such interpretation is the ‘reward deficiency syndrome’ hypothesis; it purports that both psychiatric disturbances (e.g. negative symptoms of schizophrenia) and the tendency to abuse addictive substances arise from a basic dysfunction of the dopamine mesocorticolimbic reward system.(18) The ‘primary addiction’ theory is another such explanation for comorbidity; it contends that a single neurobiological deficiency—primary abnormalities in the hippocampus and the frontal cortex—facilitate the development of schizophrenic symptoms and the person’s toxicophilia in a parallel manner.(19)
Genetic factors in the development of alcoholism
In recent decades the biological perspective on the aetiology of alcoholism has gained considerable ground. Findings from family, twin and adoption studies demonstrate that there is significantly higher risk for alcoholism among individuals with an alcoholic biological parent or first-degree relative.(20, 21, 22 and 23) Meta-analysis has been used to jointly analyze data from twin and adoption studies grouped by country of origin (Scandinavian versus United States of America). Based on all available data, genetic factors accounted for between 40 and 60 per cent of the variance in alcoholism risk, with the effects of environment (shared and non-shared) estimated between 15 and 33 per cent. In a methodologically rigorous study, Prescott and Kendler(24) examined the concordance for alcoholism among a population-based sample from the Virginia Twin Registry. Monozygotic (MZ, n = 861) and dizygotic (DZ, n = 653) male twins were diagnosed using structured interviews and DSM criteria. Concordance rates for alcohol dependence were significantly higher for MZ (48 per cent) compared to DZ (32 per cent) twins, and analyses indicated that 48-58 per cent of the variation in alcoholism liability could be attributed to additive genetic factors.
Alcoholic males with family history of alcoholism (FHP) have been reported to have greater severity of alcoholic symptoms and poorer outcomes than alcoholics that are family history negative (FHN). Box 4.2.2.1.2 describes some characteristics of familial alcoholism. Onset of drinking prior to age 15 is associated higher rates of alcoholism,(25) ADHD, conduct and anxiety disorders, as well as a host of other negative events including unintentional injuries, physical fights, nicotine/drug dependence, and poor school performance. Children of alcoholics are significantly more likely to be exposed to high-risk environments that include poor prenatal care (alcohol/nicotine exposure, nutritional deficiencies), as well as homes in which there is more poverty and violence. Overall, it
appears likely that there are common genetic and environmental influences on a host of externalizing disorders—as well as gene-environment interactions.
appears likely that there are common genetic and environmental influences on a host of externalizing disorders—as well as gene-environment interactions.
Box 4.2.2.1.2 Characteristics of familial alcoholism
Family history positive (FHP) alcoholism is associated with:
Earlier onset (<15 at age first drink is associated with increased rates of alcoholism, nicotine dependence, drug use, and conduct disorder. Early age of alcohol use is familial, heritable and may be related to transmission of disinhibitory psychopathology in males)
Behavioural disturbances during childhood (conduct disorder, emotional lability, aggressivity, low attention span, low soothability)
More severe alcohol dependence (higher levels of physical dependence, negative consequences)
Lower educational and occupational achievement
Deficits in executive cognitive functioning (poor problem solving, abstraction, and perceptual-motor skills)
Linkage studies to identify the genes underlying the heritability of alcoholism
A number of large-scale international linkage studies are currently underway that are aimed at mapping genes for alcoholism including the Irish Affected Sib Pair Study,(26) and the Collaborative Study on the Genetics of Alcoholism (COGA).(27) COGA is a multi-center program designed to detect and map susceptibility genes for alcoholism that is currently underway in the United States. Using a family-based linkage strategy, the study is examining a number of quantitative intermediary phenotypes (endophenotypes) including P300 evoked potentials, alcohol sensitivity, and personality traits (harm avoidance, novelty seeking, and reward dependence) in relation to both alcohol consumption, and alcohol dependence. In addition, the study is examining the association between polymorphisms in specific candidate genes such as alcohol dehydrogenase (ADH), monoamine oxidase (MAOB), and the serotonin transporter and alcohol-related phenotypes. In early work, COGA-reported associations between alcoholism and regions on chromosomes 4 and 15 that encode genes for the inhibitory neurotransmitter, gamma-aminobutyric acid (GABAA). Most recently, linkage and association genome scans for a broader ‘addiction’ vulnerability phenotype provided strong evidence for linkage to chromosome 4. Further assessment of single nucleotide polymorphism (SNP) genotypes within the chromosome 4 region provided strongest support for the involvement of the GABAA receptor α2 subunit (GABRA2 gene).(28) GABAA has been implicated in mediating some of the psychopharmacological effects of alcohol,(29) and the genetic studies provide convergent evidence suggesting that the predisposition to alcoholism may be inherited as a general state of CNS disinhibition/hyperexcitability that results from an altered responsiveness to GABA. However, this remains to be confirmed by additional genetic and experimental studies.
Other candidate genes and processes
It has been shown that genetic factors may influence a number of important processes such as initial sensitivity to the effects of alcohol, as well as the development of tolerance, sensitization, and physical dependence (including withdrawal complications such as seizures and delirium tremens). Several lines of research have suggested that sensitivity to alcohol may influence the propensity to abuse. Sensitivity refers to drug effects such as intoxication, physiological reactivity, and activation (tendency towards stimulation versus depression following ingestion). For example, Schuckit(30,31) found that individuals with low sensitivity to alcohol as measured by lower psychomotor responses and less subjective intoxication following alcohol dosing were more likely to be alcohol dependent at follow-up 10 years later.
Peripheral and central levels of alcohol metabolizing enzymes may be important modulators of the psychopharmacological response to alcohol. Ethyl alcohol (ethanol) is converted to acetaldehyde via the actions of alcohol dehydrogenase (ADH). There is evidence for linkage of gene(s) located on chromosome 4 (as discussed above) and two ADH genes closely linked on chromosome 4 (ADH1B and ADH1C) that encode for isozymes that differ in their kinetic properties. The allele ADH1B*2 (found largely in individuals of East Asian and Jewish descent) encodes a more active isozyme that has been associated with protection from alcohol dependence. Most recently Edenberg et al.(32) genotyped 110 SNPs across seven ADH genes in a COGA sample. There was strong evidence that variations in ADH4 were associated with alcoholism, and among African-Americans there was evidence that the ADH1B*3 allele was protective. Acetaldehyde produced by ethanol oxidation is rapidly metabolized by the enzyme aldehyde dehydrogenase (ALDH). A single base pair substitution in mitochondrial ALDH, termed the ‘oriental’ mutation (ALDH2*2 allele), is present in a large percentage of the Asian population. This mutation renders the enzyme inactive and produces a flushing response (warm-flushed face, tachycardia, nausea) following ingestion of small quantities of alcohol due to the buildup of acetaldehyde, particularly among ALDH2*2 homozygotes. Due to the aversive nature of the flushing response, the ALDH2*2 mutation is a significant protective factor against alcoholism.
Box 4.2.2.1.3 Potential candidate genes and markers for alcoholism
Brain waves (P300 event-related brain potential)
Brain enzymes (e.g. monoamine oxidase, adenylate cyclase)
Alcohol and aldehyde metabolizing enzymes (ADH, catalase, ALDH, cytochrome P450IIE1)
Opioids (e.g. kappa OPRK1receptor and prodynorphin ligand)
Serotonin (e.g. polymorphisms of the 5-HT transporter and receptors (e.g. 5-HT1B, 5-HT2A, 5-HT2C), tryptophan hydroxylase TPH (218AC))
Dopamine (polymorphisms of D2, D3, D4 receptors and the dopamine transporter (DAT))
GABA (polymorphisms in receptor subunits, variants in glutamate decarboxylase-2 (GAD2))
In addition to the examination of metabolic factors that may account for some of the genetic variance in the development of alcohol dependence, there is an intense search for other neurogenetic factors related to the effects of alcohol in the brain. As shown in Box 4.2.2.1.3, a large number of candidate markers and putative genetic loci that have been investigated to date. For example, abstinent alcoholics and approximately 35 per cent of sons of alcoholics have been shown to have lower amplitude of a P300 event-related brain potential. Analyses of COGA data indicate that P300 amplitude reduction (P3-AR) is heritable, but more recent analyses have demonstrated that the P3-AR is associated with risk for substance dependence generally (e.g. frequent use of cannabis).(33)
The analysis of various neurotransmitters (including synthesis, release, receptor density, second messengers, polymorphisms) in relation to alcoholism and other alcohol-related endophenotypes is a well-developed area of research. The high degree of comorbidity between alcoholism and other mental disorders suggests that there may be common neurobiological pathways, including those that
modulate reward, compulsive behaviour, anxiety, depression, and stress responses.(34) In this context, dysregulation of the serotonin (5HT) system has been implicated in the aetiology of a number of psychiatric disorders (depression, OCD, eating disorders) and alcoholism. In particular, polymorphisms in the promoter region of the 5HT transporter (5HTTLPR) producing the short (‘S’ allele) or long (‘L’ allele) variants differentially modulate transcriptional activity of the promoter, yielding differences in 5HT uptake activity in human platelets and brain. Most recently analyses conducted in the COGA sample have failed to find an association between the 5HTTLPR polymorphism and alcohol dependence. In a family-based association analyses (n = 1913 Caucasians) there was evidence for association of the S allele with depression, but not with alcohol dependence.(27)
modulate reward, compulsive behaviour, anxiety, depression, and stress responses.(34) In this context, dysregulation of the serotonin (5HT) system has been implicated in the aetiology of a number of psychiatric disorders (depression, OCD, eating disorders) and alcoholism. In particular, polymorphisms in the promoter region of the 5HT transporter (5HTTLPR) producing the short (‘S’ allele) or long (‘L’ allele) variants differentially modulate transcriptional activity of the promoter, yielding differences in 5HT uptake activity in human platelets and brain. Most recently analyses conducted in the COGA sample have failed to find an association between the 5HTTLPR polymorphism and alcohol dependence. In a family-based association analyses (n = 1913 Caucasians) there was evidence for association of the S allele with depression, but not with alcohol dependence.(27)
Numerous studies have examined the association between alcohol dependence and the A1 allele of the dopamine D2 receptor (DRD2), however results have been debated for more than a decade. In general, the A1 allele is not consistently associated with alcoholism, and it does not consistently co-segregate in families with alcoholism. The effect size of this allele is likely to be very small. The human genes for the dopamine D3 and D4 receptors are polymorphic and studies are currently underway examining the potential relationship between various alleles of these receptors and substance dependence.
As noted above, synaptic actions of GABA have been implicated in the psychopharmacological effects of alcohol. Associations between variants in glutamate decarboxylase-2 (GAD2), a gene encoding for a major enzyme in the synthesis of GABA have been reported. In particular a functional promoter GAD2 -243 A > G variant may influence risk for alcohol dependence in populations exhibiting severe alcoholism.(35)
In summary, plausible candidate genes for alcoholism include loci associated with alcohol and aldehyde metabolism, as well as variants within the GABA, opiate, and serotonin systems. The strongest candidate to date is for the involvement of the GABAA receptor α2 subunit (GABRA2 gene) on chromosome 4. Notably, associations between various loci and alcoholism reported in the literature have not been consistently replicated. Discrepancies in the literature have beesn attributed to variations in sampling (ethnicity, diagnostic criteria, severity of alcoholism, sample sizes), as well as to the clinical and genetic heterogeneity of alcoholism. Thus in this context, it is important to note that possible mechanisms for indirect transmission of an alcoholism phenotype include personality traits, and comorbid psychopathology including anxiety, depression, and conduct disorder.
Further information
Sartor, C.E., Lynskey, M.T., Heath, A.C., et al. (2006). The role of childhood risk factors in initiation of alcohol use and progression to alcohol dependence. Addiction, 102, 216-25.
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4.2.2.2 Alcohol dependence and alcohol problems
Jane Marshall
Introduction
The problem of excessive alcohol consumption is a major cause of public health concern in most countries of the world today. Heavy consumption, which involves far more than ‘dependence’, can cause untold misery to the individual, who is usually affected by other physical, psychological, and social disabilities as well.
As early as 1950, the World Health Organization (WHO) viewed the lack of a commonly accepted terminology as a serious obstacle to international action in the alcohol field.(1)
Definitions of ‘alcoholism’ have been proposed by a range of professional and other bodies, from biomedical scientists, medical doctors and psychiatrists, psychologists, sociologists, patients in treatment, to the general public.(2) Terms such as ‘alcoholism’, ‘addiction’, and ‘chemical dependence’, have passed into everyday speech, becoming ‘popularly enriched’ and ‘technically impoverished’.(2) These terms mean different things to different people and often have pejorative connotations. The lack of a precise definition of ‘drinking problems’ has hampered interdisciplinary communication.
In this section, the evolution of the term ‘alcohol dependence’ will be traced and put into context as but one aspect of a wider spectrum of alcohol-related problems. The concept of the alcohol dependence syndrome (ADS)(3) will be introduced and its influence on the 10th revision of the International Classification of Diseases (ICD-10)(4) and the fourth edition of the Diagnostic and Statistical Manual of Diseases (DSM-IV) will be reviewed.(5) The terms ‘harmful use’ (ICD-10) and ‘alcohol abuse’ (DSM-IV) will also be discussed. Finally ‘alcohol-related problems’ will be considered.
The development of classification systems for alcohol use disorders
From the time of its inception in 1948, WHO played a major role in formulating public health definitions of ‘alcoholism’, ‘addiction’, and ‘dependence’ through a series of expert committees. Early definitions stressed the sociological rather than the physical aspects of dependence, and thus had limited utility for biological research and psychiatric classification.
‘Alcoholism’ was classified under ‘Other non-psychotic mental disorders’ in ICD-8.(6) This definition of ‘alcoholism’ was generic, and included the subcategories of episodic excessive drinking, habitual excessive drinking, and alcohol addiction. Alcohol addiction was defined as:(6)
a state of physical and emotional dependence on regular or periodic, heavy, and uncontrolled alcohol consumption, during which the person experiences a compulsion to drink. On cessation of alcohol intake there are withdrawal symptoms, which may be severe.
In ICD-9 the term ‘alcoholism’ was dropped in favour of the ‘alcohol dependence syndrome’.(7) It was, however, still classified under the category ‘Other non-psychotic mental disorders’.
At the same time as WHO was formulating public health definitions of ‘alcoholism’, ‘addiction’, and ‘dependence’, a trend towards formal diagnostic criteria was emerging in the United States. This was driven by practical considerations such as the need for better communication between clinicians, researchers, and the general public. Other influential factors included the growing need to categorize persons in an objective fashion for legal, medical, or psychiatric reasons, to collect and communicate accurate public health information, and to standardize practice nationally and internationally. The first two editions of the Diagnostic and Statistical Manual (DSM-I and DSM-II), published in 1952 and 1968 respectively, classified ‘alcoholism’ as a category of personality disorder. In DSM-III,(8) it was included under a new and separate category of ‘Substance use disorders’. The terms ‘alcoholism’ and ‘addiction’ were dropped and the terms ‘dependence’ and ‘alcohol abuse’ were used instead. Dependence was distinguished from abuse by the presence of tolerance or withdrawal symptoms.
By the mid-1980s, DSM-III and ICD-9 were undergoing reviews for the purposes of revision. The diagnostic criteria for dependence were broadened in DSM-IIIR(9) to incorporate the elements of the alcohol dependence syndrome as hypothesized by Edwards and Gross.(3) The essential feature of the DSM-IIIR dependence category was defined in the text as a ‘cluster of cognitive, behavioural, and physiological symptoms, indicating that the person has impaired control over drinking and continues to drink despite adverse consequences’.
The alcohol dependence syndrome
Clinical description
In 1976, Edwards and Gross proposed the existence of alcohol dependence within a syndrome model.(3) Their description was based on the clinical observation that certain heavy drinkers manifested an interrelated clustering of signs and symptoms. They hypothesized that dependence was not an all-or-nothing phenomenon but existed in degrees of severity. The elements of the syndrome, as originally formulated, are summarized in Table 4.2.2.2.1. Not all the elements need always be present, nor always present with the same intensity. Edwards and Gross(3) also acknowledged the fact that not everyone who drinks too much is necessarily dependent on alcohol. They hypothesized that alcohol dependence should be conceptually distinguished from alcohol-related problems.
By drawing a clear distinction between the alcohol dependence syndrome and alcohol-related problems, Edwards and Gross introduced the concept of a bi-axial model. This was described further in the report of a WHO scientific group published in 1977.(10) Alcohol-related problems are defined as comprising those physical, psychological, and social problems that are a consequence of excessive drinking and dependence. Consumption may be viewed on a third axis.
The alcohol dependence syndrome was proposed in the first instance as an empirical formulation that would require research to confirm its assumptions. Unlike previous models of ‘alcoholism’ that had observational elements but no theoretical input, the alcohol dependence syndrome was influenced by psychological theory and proposed as a synthesis of both general learning theory and specific conditioning models of dependence.(11,12)
Establishment of the validity of the alcohol dependence syndrome
A considerable amount of scientific research evaluating the ADS has been carried out over the past 30 years, much of it supporting its validity.(13) Studies have focused on the degree to which the elements of the syndrome co-occur.(14,15) Other areas of research have included construct validity,(16) concurrent validity,(15,17,18) and predictive validity.(19,20) Field trials conducted as background to the preparation of ICD-10, DSM-IIIR, and DSM-IV, have all contributed to the body of research evidence.(5, 21, 22, 23, 24 and 25) Difficulties have been encountered in operationalizing elements such as narrowing of repertoire, subjective change, and reinstatement.(25)
These studies have shown a remarkable similarity in terms of the coherence and dimensionality of the syndrome, and are particularly impressive because of the diversity of methods and populations used.(11)
Table 4.2.2.2.1 Key elements of the alcohol dependence syndrome | ||||||||
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Individual elements of the alcohol dependence syndrome
(a) Narrowing of the drinking repertoire
Most drinkers vary their alcohol consumption from day to day and week to week. The pattern of their drinking is influenced by a range of internal cues and external circumstances. Heavy drinkers may initially widen their drinking repertoire. As dependence advances, so a diminished variability in drinking behaviour emerges. The dependent person begins to drink in the same manner every day. The daily pattern established ensures that a relatively high bloodalcohol level is maintained and that symptoms of alcohol withdrawal are avoided. As drinking becomes stereotyped with advanced dependence, dependent drinkers are able to describe their drinking day in minute detail.
(b) Salience of drinking-seeking behaviour
With advancing dependence, individuals give priority to maintaining their alcohol intake. Alcohol consumption is maintained despite painful direct consequences such as physical illness, rejection by family, and lack of money. They will ‘beg, borrow, or steal’ to obtain money for alcohol.(3)
(c) Increased tolerance to alcohol
Regular drinkers become tolerant to the central nervous system effects of alcohol and can sustain blood alcohol levels that would incapacitate the non-tolerant drinker. In short, they can ‘drink others under the table’. Tolerance may decrease in the later stages of dependence, with individuals becoming intoxicated on much less alcohol than would previously have affected them. Cross-tolerance extends to other drugs, notably barbiturates and benzodiazepines.
(d) Withdrawal symptoms
The term ‘alcohol withdrawal’ describes a broad range of symptoms and signs, from the relatively trivial to the life-threatening. At first the symptoms are intermittent and mild, but as the degree of dependence increases, so do the frequency and intensity of withdrawal symptoms. Symptoms vary from person to person and do not require abstinence to appear; they can occur when blood-alcohol concentrations are falling. When the picture is fully developed, the dependent drinker typically has severe multiple symptoms every morning on waking; these symptoms may wake him in the middle of the night. Those who are severely dependent usually experience mild withdrawal symptoms during the day whenever their alcohol levels fall.
Withdrawal symptoms cannot occur without a high degree of central nervous system tolerance, but tolerance can occur without clinically manifest withdrawal symptoms.(3)
The spectrum of symptoms is wide, but the four key symptoms are tremor, nausea, sweating, and mood disturbance. A range of other symptoms can also occur, including sensitivity to sound (hyperacusis), ringing in the ears (tinnitus), itching, muscle cramps, sleep disturbance, perceptual distortion, hallucinations, generalized (grand mal) seizures, and delirium tremens.
The four key symptoms will be described in further detail.
(i) Tremor
The first experience of alcohol withdrawal tremor may be recalled vividly: ‘One afternoon I went to cut the grass at a friend’s house. She gave me a cup of tea and my hands kept shaking. I kept rattling
the cup on the saucer and couldn’t put the cup to my mouth. I had to put them down and pretend that I had finished.’ Men often find it difficult to shave first thing in the morning and merely getting the first drink of the day to the mouth may be an ordeal in itself.
the cup on the saucer and couldn’t put the cup to my mouth. I had to put them down and pretend that I had finished.’ Men often find it difficult to shave first thing in the morning and merely getting the first drink of the day to the mouth may be an ordeal in itself.
(ii) Nausea
Dependent drinkers commonly say that their bodies want to vomit first thing in the morning, but that they have nothing to bring up. This may be described as ‘dry retching’ or ‘the dry heaves’. Typically they find it difficult to eat breakfast and to brush their teeth. The first drink of the day is often vomited back.
(iii) Sweating
Dependent drinkers commonly describe waking up in the early morning (3 a.m. or 4 a.m.) to find the bed sheets ‘drenched’. In the earlier stages of dependence they may report feeling clammy.
(iv) Mood disturbance
This is an important feature of the withdrawal syndrome. Mildly dependent individuals may feel ‘a bit edgy’. Severely dependent individuals may present with clinically significant symptoms of anxiety and depression.
(e) Relief or avoidance of withdrawal symptoms by further drinking
In the early stages of dependence, individuals may find that they need a lunchtime drink to alleviate discomfort. As dependence progresses there emerges the need for an early morning drink to relieve the symptoms of alcohol withdrawal coming on after a night’s abstinence. Later, individuals may wake in the middle of the night for a drink, and alcohol is often kept by the bed. If they have to go for 3 or 4 hr without a drink during the day, they value the next drink for its relief effect.
Clues to the degree of dependence can be obtained by taking a detailed history of the first drink of the day. The person drinking from a bottle kept by the side of the bed before they get up is more dependent than the person who has breakfast and reads the paper first. The woman who pours whisky into her first cup of tea is more dependent than the librarian who slips out to the lavatory at midday to drink from a quarter bottle of vodka hidden in her handbag.
(f) Subjective awareness of compulsion to drink
This describes an altered subjective experience of an inability to limit drinking to an acceptable level. Although the familiar term ‘loss of control’ has been used to denote this element, it is more likely that control has been ‘impaired’ rather than lost.
Another complex experience is that of ‘craving’, the subjective experience of which is greatly influenced by environment. Individuals can experience craving of very different intensities on different occasions. Cues for craving include the experience of intoxication, the withdrawal syndrome, mood (anger, depression, elation), or situational cues (being in a pub or (bar), passing an off-licence (liquor store).
Here the key experience may best be described as a compulsion to drink. The desire for a further drink is seen as irrational, and is resisted, but despite this a further drink is taken.
(g) Reinstatement after abstinence
Alcohol dependent individuals who begin to drink again after a period of abstinence invariably relapse back into the previous stage of the dependence syndrome. This process occurs over a variable time course, with moderately dependent individuals perhaps taking weeks or months and severely dependent individuals taking a couple of days.
Influence of the alcohol dependence syndrome on ICD-10 and DSM-IV
Both DSM-IV and ICD-10 diagnostic approaches have drawn on the original concept of the alcohol dependence syndrome.(26,27) Although they have undoubtedly contributed to the standardization of psychiatric practice nationally and internationally, they picture dependence as an all-or-nothing phenomenon rather than as a dimensional state.(28)
ICD-10(4)
ICD-10 includes six items under dependence, most of which are similar to DSM-IV. For a diagnosis of dependence, three or more items should have occurred in the past year. The ‘strong desire or sense of compulsion to take the substance’ is viewed as a central descriptive characteristic of dependence in ICD-10. This compulsiveuse indicator is not included in the DSM-IV concept of dependence (Table 4.2.2.2.2).
DSM-IV(5)
In view of the major changes in criteria that had occurred between 1980 and 1987, the DSM-IV Substance Use Disorders Work Group was reluctant to make any additional major changes to DSM-IIIR. The repetitive nature of the problem was highlighted in that three or more of the items should have occurred during the same 12-month period and the associated difficulties must have led to clinically significant impairment or distress. DSM-IV also uniquely allows for the subtyping of dependence with and without physiological dependence (Table 4.2.2.2.2).
Alcohol abuse and harmful use
Alcohol abuse
DSM-III; DSM-IIIR; DSM-IV
The term ‘alcohol abuse’ appeared infrequently in the American literature before 1970, when the United States National Institute on Alcohol Abuse and Alcoholism was formed. It was adopted as a formal diagnostic category by DSM-III,(8) which defined abuse as a behavioural concept: ‘A pattern of pathological use for at least a month that causes impairment in social or occupational functioning’. Although enshrined in DSM-IIIR and DSM-IV, the term ‘abuse’ has been variously regarded as ‘unscientific and pejorative’(29) and ‘oppobrious’ and ‘vindictive’.(30)
The DSM-IV Substance Use Disorders Workgroup carried out extensive analysis in an effort to define abuse more precisely. Accordingly, in DSM-IV, four separate items, not included in dependence, are listed for the diagnosis of abuse, focusing on social, physical, legal, and interpersonal problems associated with alcohol use. These problems must have occurred repeatedly over a 12-month period, and caused ‘clinically significant impairment or distress’ (Table 4.2.2.2.3). In practice, the DSM-IV alcohol abuse definition includes a mixture of dependence and harm criteria which could be scaled along a single continuum of severity of alcohol dependence.
Table 4.2.2.2.2 Comparison of ICD-10 and DSM-IV criteria for substance dependence | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Table 4.2.2.2.3 Comparison of criteria for abuse or harmful use of substances | ||||||||||||||||||||||||||
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Harmful use
(a) ICD-10
The ICD-10 criteria for harmful use of alcohol differ significantly from the DSM-IV abuse classification. An ICD-10 diagnosis of harmful drinking requires a pattern of drinking that has caused actual physical or psychological harm to the user. This definition excludes social harms such as marital problems and does not overlap with the DSM-IV definition of alcohol abuse.
The future
Revision of the DSM and ICD classification systems must address the fact that the current systems do not address the continuum of severity of alcohol use disorders (AUDs). Research is needed to explore the relationship between AUDs and the quantity, frequency, and pattern of drinking.(31) Further refinements of the alcohol dependence diagnosis should focus on the essential or core features of the disorder.
Alcohol-related problems
Not everyone experiencing an alcohol problem or alcohol-related disability will be suffering from alcohol dependence. Both dependent and non-dependent drinkers, particularly binge drinkers, are at risk of problems related to heavy alcohol consumption. Indeed, epidemiological evidence supports the view that most alcohol-related
harm in the general population occurs in heavy non-dependent drinkers.
harm in the general population occurs in heavy non-dependent drinkers.
Alcohol-related problems are extremely diverse. They have been defined as ‘those problems that may arise in individuals around their use of beverage alcohol, and that may require an appropriate treatment response for their optimum management’.(32) The phrases ‘alcohol problems’ or ‘alcohol-related problem’ contain an assumption of causality.(33) This issue is a complex one, involving individual differences and the social context of drinking as well as the pattern, duration, and intensity of alcohol use.
Alcohol-related problems can be related to the acute or chronic consumption of alcohol. A fractured ankle sustained by falling over while acutely intoxicated is an example of the former category. Cirrhosis of the liver is an example of a chronic problem. An individual who drinks in binges will experience different problems compared with someone who drinks the same amount of alcohol spread out over a week or a month or a year. The way in which a person behaves while intoxicated is another important factor determining the nature of alcohol-related problems. The social consequences of drinking such as job loss, imprisonment, marital and family break-up, and drunk-driving have profound effects on the well being of the drinker, their family, and society.(33)
Types of alcohol-related problems
Although somewhat artificial, it is helpful to classify alcohol-related problems in individuals into physical, psychological, and social categories. There is often considerable overlap between these three areas. The more severe the dependence, the greater the likelihood of problems of all three kinds.(18)
Alcohol-related physical and psychological problems are discussed in the next section. Some of the social problems can be included here, for example the acute adverse consequences of drinking such as trauma resulting from road traffic accidents, injuries from fights, and death from overdose.(33)
The social problems that can result from drinking are legion. Alcohol is involved in all types of accidents and contributes to traffic deaths, home, and leisure injuries.(33) It is associated with domestic violence, child abuse, crime, homicide, and suicide and is also related to poor work performance, dismissal, unemployment, debt and housing problems, and crimes of violence.
There is a continuity between moderate and excessive drinking and between harmless drinking and drinking that results in harm or in problems. Such problem-clustering may reflect alcohol dependence, certainly amongst a proportion of these drinkers. Given this heterogeneity, no one form of treatment is likely to be effective for all individuals with alcohol problems.(32) A range of treatments is required and it should be possible for non-specialists to offer brief interventions (see Chapter 4.2.2.4).
The study of alcohol-related problems remains underdeveloped, compared with the study of alcohol dependence.(34) There may be several reasons for this, not least the difficulties inherent in measuring alcohol-related problems. Another important issue, central to these difficulties, is the extent to which alcohol is causally related to the problem.
Several questionnaires, measuring a variety of alcohol-related problems, have been developed. The Alcohol Problems Questionnaire (APQ)(34) is a standardized inventory, which includes 46 items covering eight problem domains: physical, psychological, friends, finances, police, marital, children, and work. All questions apply to the 6-month period prior to the completion of the questionnaire. The shorter or core version includes the first five domains (23 items). This questionnaire can make a useful contribution to the overall assessment, and is of potential value in outcome research.
Conclusions
An understanding of the concepts of alcohol dependence and alcohol-related problems is central to the therapeutic process with individual patients.
The development of diagnostic criteria has helped to standardize practice nationally and internationally, and aided interdisciplinary communication. The diagnostic criteria for dependence are imperfect because they view the syndrome as an all-or-nothing phenomenon rather than as a dimensional state. The concepts of abuse and harmful use need further refinement. The totality of alcohol problems is a vast area with major implications for the general population, not just dependent drinkers.
Further information
Reports and reviews
Raistrick D., Heather N., Godfrey, C (2006). Review of the effectiveness of treatment for drinking problems. London: National Treatment Agency for Substance Misuse. This review is eminently readable summary of the published international research literature on alcohol interventions and treatment. Chapter 2 describes the categories of alcohol misuse, and sets them in the context of treatment and interventions to reduce alcohol-related harm.
Room, R., Babor, T., Rehm, J. (2005). Alcohol and public health. Lancet, 365, 510-530
Compilation of articles
Saunders, J. B.and Schuckit, M. A. (2006). Diagnostic issues in substance use disorders: refining the research agenda. Addiction (Suppl 1), 101, 1-173. A series of 18 articles commissioned by the Substance Use Disorders Workgroup to inform the research agenda for the development of the Vth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V).
Marshall E. J, Farrell, M. Chapter editors. Addiction Psychiatry. Psychiatry, 5, 421-63. Straightforward account of the classification and epidemiology of substance use disorders.
Book
Edwards, G. (2006). Alcohol: the ambiguous molecule. Harmondsworth, Penguin.
References
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2. Babor, T.F. (1990). Social, scientific and medical issues in the definition of alcohol and drug dependence. In The nature of drug dependence (ed. G. Edwards and M. Lader), pp. 19-36. Oxford Medical Publications, Oxford.
3. Edwards, G. and Gross, M.M. (1976). Alcohol dependence: provisional description of a clinical syndrome. British Medical Journal, 1, 1058-61.
4. World Health Organization (1992). International statistical classification of diseases and related health problems, 10th revision. WHO, Geneva.
5. American Psychiatric Association (1994). Diagnostic and statistical classification of diseases and related health problems (4th edn). American Psychiatric Association, Washington, DC.
6. World Health Organization (1974). Glossary of mental disorders and guide to their classification: for use in conjunction with the International Classification of Diseases (8th revision). WHO, Geneva.
7. World Health Organization (1978). Mental disorders: glossary and guide to their classification in accordance with the Ninth Revision of the International Classification of Diseases. WHO, Geneva.
8. American Psychiatric Association (1980). Diagnostic and statistical manual of mental disorders (3rd edn). American Psychiatric Association, Washington, DC.
9. American Psychiatric Association (1987). Diagnostic and statistical manual of mental disorders (3rd edn, revised). American Psychiatric Association, Washington, DC.
10. Edwards, G., Gross, M.M., Keller, M., Moser, J., and Room, R. (1977). Alcohol-related disabilities. WHO Offset Publication No. 32. WHO, Geneva.
11. Edwards, G. (1986). The alcohol dependence syndrome: a concept as stimulus to enquiry. British Journal of Addiction, 81, 171-83.
12. Babor, T.F., Cooney, N.L., and Lauerman, R.J. (1987). The dependence syndrome concept as a psychological theory of relapse behaviour: an empirical evaluation of alcoholic and opiate addicts. British Journal of Addiction, 82, 393-405.
13. Li, T.K., Hewitt, B.G., Grant, B.F (2007). The alcohol dependence syndrome, 30 years later: a commentary. Addiction, 102, 1522-30.
14. Chick, J. (1980). Alcohol dependence: methodological issues in its measurement, reliability of the criteria. British Journal of Addiction, 75, 175-86.
15. Stockwell, T., Murphy, D., and Hodgson, R. (1983). The severity of alcohol dependence questionnaire: its use, reliability and validity. British Journal of Addiction, 78, 145-55.
16. Feingold, A. and Rounsaville, B. (1995). Construct validity of the dependence syndrome as measured by DSM-IV for different psycho-active substances. Addiction, 90, 1661-9.
17. Kivlahan, D., Sher, K.J., and Donovan, D.M. (1989) The Alcohol Dependence Scale: a validation study among inpatient alcoholics. Journal of Studies on Alcohol, 50, 170-5.
18. Caetano, R. (1993). The association between severity of DSM-III-R alcohol dependence and medical and social consequences. Addiction, 88, 631-42.
19. Hodgson, R., Rankin, H.J., and Stockwell, T. (1979). Alcohol dependence and the priming effect. Behaviour Research and Therapy, 17, 379-87.
20. Rankin, H., Stockwell, T., and Hodgson, R. (1982). Cues for drinking and degrees of alcohol dependence. British Journal of Addiction, 77, 287-96.
21. Grant, B.F., Harfold, T.C., Chou, P., et al. (1992). DSM-III-R and the proposed DSM-IV alcohol use disorders. United States 1988. A methodological comparison. Alcoholism, Clinical and Experimental Research, 16, 215-21.
22. Cottler, L.B. (1993). Comparing DSM-III-R and ICD-10 substance use disorders. Addiction, 88, 689-96.
23. Rapaport, M.H., Tipp, J.E., and Schuckit, M.A. (1993). A comparison of ICD-10 and DSM-III-R criteria for substance abuse and dependence. American Journal of Drug and Alcohol Abuse, 19, 143-51.
24. Rounsaville, B.J., Bryant, K., Babor, T., et al. (1993). Cross system agreement for substance use disorders: DSM-III-R, DSM-IV and ICD-10. Addiction, 88, 337-48.
25. Cottler, L.B., Phelps, D.L., and Compton, W.M. (1995) Narrowing of the drinking repertoire criterion: should it have been dropped from ICD-10? Journal of Studies on Alcohol, 56, 173-6.
26. Saunders, J.B. (2006). Substance dependence and non-dependence in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD): can an identical conceptualization be achieved? Addiction,101, 48-58.
27. Grant, B. (1996). DSM-IV, DSM-III-R, ICD-10 alcohol and drug abuse/harmful use and dependence, United States, 1992: a nosological comparison. Alcoholism, Clinical and Experimental Research, 8, 1481-8.
28. Edwards, G., Marshall, E.J., and Cook, C.C.H. (2003). The treatment of drinking problems (4th edn). Cambridge University Press.
29. Edwards, G., Arif, A., and Hodgson, R. (1981). Nomenclature and classification of drug- and alcohol-related problems: a WHO memorandum. Bulletin of the World Health Organization, 50, 225-42.
30. Keller, M. (1982). On defining alcoholism: with comment on some other relevant words. In Alcohol, science and society revisited (ed. E.L. Gomberg, H.R. White, and J.A. Carpenter), pp. 119-33. University of Michigan Press, Ann Arbor, MI.
31. Hasin, D.S., Liu, X., Alderson, D., et al. (2006) DSM-IV alcohol dependence: a categorical or dimensional phenotype? Psychological Medicine, 36, 1695-1705.
32. Institute of Medicine (1990). Broadening the base of treatment for alcohol problems: report of a study by a Committee of the Institute of Medicine, Division of Mental Health and Behavioural Medicine. National Academy Press, Washington, DC.
33. Babor, T.F., Caetano, R., Casswell, S., et al. ((2003). Alcohol: No ordinary commodity. Research and Public Policy. Oxford University Press.
34. Drummond, D.C. (1990). The relationship between alcohol dependence and alcohol-related problems in a clinical population. British Journal of Addiction, 85, 357-66.
4.2.2.3 Alcohol and psychiatric and physical disorders
Karl F. Mann
Falk Kiefer
Intoxication
Clinical symptoms of alcohol intoxication are associated with both, blood alcohol concentration (BAC), and the individual’s level of tolerance. Whereas in healthy persons without alcohol tolerance mild intoxication (BAC ≤ 100 mg per cent), medium intoxication (BAC 100-200 mg per cent), and severe intoxication (BAC >200 mg per cent) differ clinically, this schema does not work in patients suffering from alcoholism. In these people, different levels of tolerance can lead to completely different clinical pictures despite their having similar blood alcohol concentrations. Thus, psychopathology is more important than blood alcohol concentrations for estimating the severity of an acute intoxication state. With increasing BAC we observe elated mood, disinhibition, impaired judgement, belligerence, impaired social and occupational functioning, mood lability, cognitive impairment, reduced attention span, slurred speech, incoordination, unsteady gait, nystagmus, and stupor or coma.
The term ‘pathological intoxication’ can still be found in the older literature (reviewed by Lishman(1)). It was described as an outburst of aggression and uncontrollable rage, which might have led to serious destructions. As a rule, this behaviour, which was not typical for the individual, ended in terminal sleep and subsequent amnesia. However, since there is not enough empirical evidence for the existence of this syndrome, it was no longer considered in DSM-IV.(2)
Alcohol-induced amnesias (‘blackouts’)
This term refers to a transient state of amnesia after drinking excess. Usually patients’ behaviour is no different from their behaviour during other periods of intoxication without blackouts. Nevertheless, the memory gap usually lasts for hours, but may be as long as a day or more. In extreme cases, patients find themselves in strange places with no recollection of how they got there.
Withdrawal
Withdrawal without complications
When alcohol is used regularly and withdrawn rapidly, a characteristic withdrawal syndrome can develop. It includes autonomic hyperactivity like hand tremor, insomnia, sweating, tachycardia, hypertension, and anxiety. The symptoms generally occur between 6 and 12 h after the last alcohol consumption. Depending on their severity they may last for up to 4 or 5 days. The neurobiological basis for withdrawal is a gradual upregulation of N-methyl-D-aspartate receptors under the influence of chronic alcohol use. As soon as the alcohol, which acts as a central nervous system depressant, is withdrawn, an overwhelming excitatory action in the brain mediated by the glutamatergic system is observed.
Withdrawal with perceptual disturbances
The individual usually experiences more discomfort and anxiety if transient visual, tactile, or auditory hallucinations or illusions are present. In this state, reality testing is still intact: the person still knows that the hallucinations are induced by the substance. If this is no longer true, a substance-induced psychotic disorder or a delirium tremens is likely.
Withdrawal with grand mal seizures (alcoholic
convulsions, ‘rum fits’) In about 30 per cent of the cases the typical grand mal seizures are followed by a delirium tremens. The electroencephalograph picture is only abnormal at the time of the fits, hence, alcohol convulsions differ pathophysiologically from latent epilepsy.
Alcohol-induced psychosis (delirium tremens)
In delirium tremens the symptoms of alcohol withdrawal described earlier are accompanied by a reduced level of consciousness, disorientation in time and place, impairment of recent memory, insomnia, and perceptual disturbances. The latter include misinterpretation of sensory stimuli and hallucinations; most are visual, but auditory and haptic hallucinations also occur. The hallucinations may be Lilliputian or of normal size, and may be of complex, frightening, and extremely realistic scenes. The patient is restless and fearful, and may become severely agitated. There is marked tremor, and ataxia when standing. Some patients experience vestibular disturbance. Autonomic disturbance includes sweating, tachycardia, raised blood pressure, and dilated pupils. There may be a mild pyrexia. Patients are usually dehydrated, often with abnormal electrolytes, leucocytosis, and impaired liver function. As in other forms of delirium, symptoms are worse at night.
Delirium tremens is the most severe of the states following withdrawal of alcohol, with a reported mortality of up to 5 per cent. In its fully developed form it is uncommon; the more frequent states are acute tremulousness, transient hallucinations with tremor, and uncomplicated fits. Delirium tremens usually begins after 3 to 4 days of abstinence from alcohol, although occasionally it starts while drinking continues. In the latter cases it is assumed that alcohol levels have fallen below a critical level. It is not known by what mechanism alcohol withdrawal leads to the clinical syndrome. Delirium tremens often appears to start suddenly, although close enquiry may reveal a prodromal stage of restlessness, anxiety, and insomnia. It usually lasts for 2 to 3 days, often ending with deep and prolonged sleep from which thepatient wakes symptom free and with little memory of the period of delirium. Rarely, the patient is left with an amnesic syndrome, perhaps the consequence of previous undetected Wernicke’s encephalopathy.
Treatment is by sedation, usually with a benzodiazepine, together with fluid replacement under close observation. The possibility of accompanying head injury or infection should be investigated. Sedation should be adequate to prevent withdrawal seizures, with frequent monitoring of the response. High-potency vitamins are usually given to prevent Wernicke’s encephalopathy. An anticonvulsant is given when there have been withdrawal seizures in the past. Cardiovascular collapse and hyperthermia occur occasionally and require urgent medical treatment.
Hallucinosis
Alcoholic hallucinosis is a rare condition in which auditory hallucinations are present in clear consciousness and without autonomic overactivity, usually in a person who has been drinking excessively for many years. The hallucinations often begin as simple noises, but are gradually replaced by voices, which may threaten, abuse, or reproach the person. Usually the voices speak to the person, but sometimes they discuss him or her in the third person. The voices may be occasional or relentlessly persistent. They may command the patient, who may respond with unrestrained or suicidal behaviour. Delusions are secondary interpretations of the hallucinations. Autochthonous hallucinations suggest schizophrenia, as do thought disorder or incongruity of affect. The patient is usually distressed, anxious, and restless.
In both ICD-10 and DSM-IV, the disorder is classified as a substance-induced psychotic disorder and not, as has been suggested in the past, a form of schizophrenia (released by heavy drinking). The differential diagnosis includes transient auditory hallucinations occurring during withdrawal from a period of heavy drinking, and delirium tremens in which auditory hallucinations may accompany the more prominent visual ones. In both conditions the auditory hallucinations are transient and disorganized, and in the latter consciousness is impaired. In contrast, the auditory hallucinations of an alcoholic hallucinosis are persistent and organized, and occur in clear consciousness. Other differential diagnoses are depressive disorder with psychotic symptoms and schizophrenia, both of which can be accompanied by heavy drinking.
The hallucinations usually respond rapidly to antipsychotic medication. The prognosis is good; usually the condition improves within days or a couple of weeks provided that the person remains abstinent. Symptoms that last for 6 months generally continue for years.(3)
Psychiatric disorders
Alcohol-dependent patients often present with symptoms of anxiety or depression. These states are generally referred to as
comorbid disorders or dual diagnosis. Alcoholism can be a consequence of anxiety and mood disorders (‘secondary alcoholism’). It can develop independently after anxiety and depression, or it can precede anxiety and depressive symptoms (‘primary’). As the former are discussed elsewhere in this textbook, here we concentrate on the latter.
comorbid disorders or dual diagnosis. Alcoholism can be a consequence of anxiety and mood disorders (‘secondary alcoholism’). It can develop independently after anxiety and depression, or it can precede anxiety and depressive symptoms (‘primary’). As the former are discussed elsewhere in this textbook, here we concentrate on the latter.
Alcohol-induced mood disorders
Alcohol is a central nervous system depressant. Taken regularly in high doses it may provoke feelings of sadness. Episodes of withdrawal or relative withdrawal can lead to excitability and nervousness, including anxiety. The more a person drinks, the more likely it is that these symptoms will occur. Finally in the stage of alcohol dependence, up to 80 per cent of people report depressive symptoms at some time in their life. About one-third of male patients and up to 50 per cent of female patients have experienced longer periods of severe depression.(4) These high prevalence rates are noteworthy, since more than 20 per cent of alcoholics have attempted suicide once or more and about 15 per cent die in their attempt. Besides depressive features, alcohol-induced mood disorders may also comprise manic symptoms or mixed features. However, the diagnosis should only be used when the symptoms cause clinically significant impairment or distress in social, occupational, or other areas of functioning.
Concerning treatment, it is interesting to note that despite the vast majority of patients who present with depressive symptoms at the beginning of treatment for alcoholism, only very few need specific antidepressant medication or specific psychotherapy. In most other cases depressive symptoms disappear within weeks of controlled abstinence.(5)
Alcohol-induced anxiety disorders
This diagnosis should only be used when anxiety symptoms are thought to be related to the direct physiological effects of alcohol. The symptomatology may involve anxiety, panic attacks, and phobias. Both alcohol-induced anxiety disorders and mood disorders can develop during intoxication, withdrawal, or up to 4 weeks after cessation of alcohol consumption. During intoxication or withdrawal, the diagnosis should only be given when the symptomatology clearly exceeds what would be expected from anxiety or depressive symptoms during a regular intoxication or withdrawal episode.
Anxiety disorders are among the most common groups of psychiatric disorders in the general population, with prevalence rates of up to 25 per cent.(6) In clinical studies between 20 and 70 per cent of patients with alcoholism also suffer from anxiety disorders.(7) On the other hand, between 20 and 45 per cent of patients with anxiety disorders also have histories of alcoholism.(8) However, it has been argued that the comorbidity figures are overestimated, because in some of the studies the focus was on drinking patterns rather than on alcohol dependence or they describe anxiety symptoms rather than disorders according to diagnostic criteria.(9) Family studies analysing the comorbidity of alcoholism and anxiety disorders might be a means of clarifying this controversy. For instance, in the Yale study the presence of anxiety disorders in the probands slightly increased the risk for alcohol dependence in their relatives, whereas alcohol dependence in the proband did not increase their relative’s risk for anxiety disorders.(10) Similarly, Maier et al.(11) demonstrated an increased risk of alcoholism in probands with panic disorders, but not the reverse. Kendler et al.(12) in a study of female twins, found evidence that common genetic factors may underlie both alcoholism and panic disorder.
Effects on the brain
Cerebral cortex
Chronic alcohol consumption leads to structural and functional changes in the brain. Alcoholic dementia is dealt with in Chapter 4.1.11. Most of the tissue loss from the cerebral hemispheres in alcoholics is accounted for by a reduction in the volume of the cerebral white matter, additionally there is a slight reduction in the volume of the cerebral cortex. This has been demonstrated both pathologically(13) and using magnetic resonance imaging with quantitative morphometry.(14)
Harper et al.(15) documented neuronal loss in alcoholics. There was a 22 per cent reduction in the number of neurones in the superior frontal cortex (Brodmann’s area 8), while surviving neurones showed shrinkage in the superior frontal, motor, and frontal cingulate cortices.(16) This finding of cortical damage in alcoholics is consistent with neuroradiological studies.(14)
Ferrer et al.(17) examined the dendritic tree of cortical neurones in alcoholic subjects using Golgi-apparatus impregnation techniques. They described a significant reduction in the basal dendritic tree of layer III pyramidal neurones in both the superior frontal and motor cortices. These studies suggest that, even though there is no significant reduction in the numbers of cortical neurones in the motor cortex, there are cellular structural abnormalities that could have important functional implications.
Wernicke’s encephalopathy
The best-known features of heavy alcohol consumption in adults are Wernicke’s encephalopathy and Korsakoff’s syndrome. Wernicke’s encephalopathy is directly caused by thiamine deficiency, which results from a combination of inadequate dietary intake, reduced gastrointestinal absorption, decreased hepatic storage, and impaired utilization. Only a subset of thiamine-deficient alcoholics develop Wernicke’s encephalopathy, perhaps because they have inherited or acquired abnormalities of the thiamine-dependent enzyme transketolase, which reduces its affinity for thiamine. Wernicke’s encephalopathy is characterized by degenerative changes, including gliosis and small haemorrhages in structures surrounding the third ventricle and aqueduct: namely, the mammillary bodies, hypothalamus, mediodorsal thalamic nucleus, colliculi, and midbrain tegmentum. Clinical features associated with the Wernicke-Korsakoff syndrome include memory deficits, ocular signs, ataxia, and global confusional states. Most can be related to damaged functional systems in the hypothalamus, midbrain, and cerebellum. In a large Scandinavian neuropathological study, 12.5 per cent of all alcoholics exhibited signs of Wernicke’s encephalopathy.(18)
Korsakoff’s syndrome
About 80 per cent of alcoholic patients recovering from Wernicke’s encephalopathy develop Korsakoff’s amnesic syndrome. It is characterized by marked deficits in anterograde and retrograde memory, apathy, an intact sensorium, and relative preservation of other intellectual abilities. Korsakoff’s amnesic syndrome may also appear without an antecedent episode of Wernicke’s
encephalopathy. Acute lesions may be superimposed on chronic lesions, suggesting that subclinical episodes of Wernicke’s encephalopathy may culminate in Korsakoff’s amnesic syndrome. The memory disorder correlates best with the presence of histopathological lesions in the dorsomedial thalamus. (Amnesic syndrome is considered further in Chapter 4.1.12.)
encephalopathy. Acute lesions may be superimposed on chronic lesions, suggesting that subclinical episodes of Wernicke’s encephalopathy may culminate in Korsakoff’s amnesic syndrome. The memory disorder correlates best with the presence of histopathological lesions in the dorsomedial thalamus. (Amnesic syndrome is considered further in Chapter 4.1.12.)
Cerebellar degeneration
Many alcoholic patients develop a chronic cerebellar syndrome related to the degeneration of Purkinje cells in the cerebellar cortex. Quantitative studies revealed a significant loss of cerebellar Purkinje cells (by 10-35 per cent) and shrinkage of the cerebellar vermal, molecular, and granular cell layers.(19) Evidence for a direct toxic effect caused by ethanol is provided by animal models.(20) In neuroimaging studies, however, cerebellar ataxia in alcoholics does not correlate with the daily, annual, or lifetime consumption of ethanol. As in Wernicke’s encephalopathy, thiamine deficiency due to poor nutrition has also been implicated. Cerebellar atrophy has been reported to occur in about 40 per cent of chronic alcoholics.(19) In a clinical study of alcoholic inpatients, 49 per cent had at least discrete clinical signs of cerebellar atrophy.(21)
The diagnosis of alcoholic cerebellar ataxia is based on the clinical history and neurological examination. The ataxia affects the gait most severely. Limb ataxia and dysarthria occur more often than in Wernicke’s encephalopathy, whereas nystagmus is rare. Computed tomography or magnetic resonance imaging scans may show cerebellar cortical atrophy, but a considerable number of alcoholic patients with this finding are not ataxic on examination. Whether these represent subclinical cases in which symptoms will develop subsequently is unclear. It is interesting to note that impaired cerebellar function improves significantly when abstinence is maintained.(22)
Hepatocerebral degeneration
Hepatic encephalopathy develops in many alcoholics with liver disease, and is characterized by altered sensorium, frontal release signs, ‘metabolic’ flapping tremor, hyperreflexia, extensor plantar responses, and occasional seizures. Whereas some patients progress from stupor to coma and then death, others recover and suffer recurrent episodes. The brains of patients with hepatic encephalopathy show enlargement and proliferation of protoplasmic astrocytes in the basal ganglia, thalamus, red nucleus, pons, and cerebellum, in the absence of neuronal loss or other glial changes.(23)
Patients who do not recover fully after an episode of hepatic encephalopathy go on to develop a progressive syndrome of tremor, choreoathetosis, dysarthria, gait ataxia, and dementia. Hepatocerebral degeneration may progress in a stepwise fashion, with incomplete recovery after each episode of hepatic encephalopathy, or slowly and inexorably, without a discrete episode of encephalopathy.
Rare disorders
The Marchiafava-Bignami syndrome is a disorder of demyelination or necrosis of the corpus callosum and adjacent subcortical white matter. The course may be acute, subacute, or chronic, and is marked by dementia, spasticity, dysarthria, and an inability to walk. Patients may lapse into coma and die, survive for many years in a demential condition, or occasionally recover.
Central pontine myelinolysis is a disorder of the cerebral white matter that usually affects alcoholics, but it also occurs in non-alcoholics with liver disease including Wilson’s disease, malnutrition, anorexia, burns, cancer, Addison’s disease, and severe electrolyte disorders such as thiazide-induced hyponatraemia; however, the majority of cases occur in alcoholics, suggesting that alcoholism may contribute to the genesis of central pontine myelinolysis in, as yet, undefined ways.(23) Myelinolytic lesions can be reduced experimentally by rapid correction of chronic hyponatraemia. Symptoms include loss of pain sensation in the limbs, bulbar palsy, quadriplegia, disordered eye movements, vomiting, confusion, and coma.
Reversibility of brain damage
Alcohol-related neuroanatomical brain changes have been shown to be partially reversible. These findings created an ongoing debate on possible mechanisms and clinical correlates.(22)
Foetal alcohol syndrome
The first description of the foetal alcohol syndrome was given by French scientists in 1968.(24) As a research paradigm, it has a major impact on our understanding of alcohol’s effects on the brain. Clinically the syndrome is characterized by: growth retardation involving height, weight, and head circumference; deficient intellectual and social performance and muscular coordination; minor structural anomalies of the face, together with more variable involvement of the limbs and the heart.
The basis of this pathology is a cascade of effects exerted by alcohol on the developing cell. Under normal conditions growth factors enhance the growth of cells and their differentiation, but alcohol can diminish these effects.(25) A second way of damaging the developing nerve cell is through the production of free radicals that allow calcium to accumulate in the cells.(26) The induction of a free-radical formation is induced by alcohol. The result of both pathogenic processes is a decrease in the overall size of the brain and a diminution in the thickness of the outer layers of the cortex, due to decreases in the total numbers of cells. Impaired nerve cell migration might also play a role in the development of the foetal alcohol syndrome.(27)
The effects of alcohol on the developing brain are clinically measured by assessing the head circumference, with a clear dose-dependent effect.
The foetal alcohol syndrome is considered further in Chapter 9.2.7.
Effects on the body
Malnutrition and vitamin deficiency
Malnutrition can be a consequence of deficient food intake. More important in alcoholics seem to be maldigestion and malabsorbtion (‘secondary malnutrition’). Apart from the direct toxic effect of alcohol on most body tissues, malnutrition is an important contributor to organ damage in alcoholics.(28) Vitamin metabolism may be profoundly affected by chronic alcohol consumption. As a consequence, many alcoholics have deficiencies in vitamins B1 (thiamine), A, D, B6, and E, and folate. This can lead to a variety of physical consequences, including damage to different organs.
Peripheral neuropathy
Besides its effect on the central nervous system, alcohol also damages motor, sensory, and autonomic nerves that control muscles and internal organs. Symptoms are weakness, numbness, pain, and a prickly feeling or burning of the skin, especially the feet. Usually on neurological examination, the tendon reflexes are diminished or have completely disappeared and skin sensibility is reduced, especially in the feet and in the lower limbs. When patients abstain from alcohol, the progression of the symptoms can be stopped and even partial recovery is possible.
Muscle
Alcohol is toxic to skeletal muscles in a dose-dependent way. Alcoholics often suffer from malnutrition, which adds to the chronic changes in muscles. Chronic myopathy can be found in 40 to 60 per cent of alcohol-dependent patients.(29) Pathophysiological mechanisms of muscle damage include alterations in membrane fluidity, ion channels, and pumps, as well as protein synthesis and hormonal dysfunction. Patients complain of pain and weakness. Swelling of the muscle can be easily detected. In chronic states, muscle atrophy is evident. There is no acute treatment for alcoholic myopathy other than abstinence, when acute myopathy can rapidly disappear; chronic myopathy usually only improves, leaving persistent weaknesses.
Liver
The effects of ethanol on the liver are among the first and best-known symptoms of alcoholism. The first manifestation of alcoholic liver diseases is the fatty liver. It is followed by early fibrosis, which can be associated with alcoholic hepatitis. If the process continues, irreversible damage leading to severe fibrosis and to cirrhosis is observed.(30) These effects occur through heavy alcohol consumption even in the absence of dietary deficiencies.
Mortality from liver cirrhosis has long been an important correlate of the per capita consumption in a given population. Liver damage is also important because it produces an increase in liver enzymes such as aspartate transaminase, alanine transaminase, and γ-glutamyl transferase, which again are of great practical value as diagnostic markers of severe alcohol consumption. Alcohol accounts for more than 80 per cent of all cirrhosis deaths, a consequence that seems to be even more pronounced in women.(31)
Pancreas
About 5 per cent of alcoholics develop chronic pancreatitis. Ethanol seems to damage the pancreas slowly. In general, it takes between 10 and 15 years of heavy drinking before pancreatitis becomes clinically apparent. In the presomatic phase certain changes such as fibrosis, calcium deposits, and especially loss of functioning in enzyme- and hormone-producing cells can be demonstrated. The acute symptoms are abdominal pain and vomiting. Chronic complications include weight loss, steatorrhoea, and diabetes mellitus.(32)
Skin
Originally it was believed that skin alterations in alcoholics are due to alcoholic liver disease. However, more recent research has revealed that the skin may be affected much earlier by alcohol misuse.(33) Whereas the palmar erythema and spider naevi are well-known consequences of alcoholic liver disease, which also serve as diagnostic markers for alcoholism, psoriasis and facial erythema have less often been linked with high alcohol consumption. Alcohol clearly has to be on the list of agents known to exacerbate psoriasis. One possible mechanism of the action of alcohol on the skin could be a defect in the immune system.
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