Alcohol and psychiatric and physical disorders
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 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When alcohol is used regularly and withdrawn rapidly, a characteristic withdrawal syndrome can develop.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.
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)
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.
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
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.
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)
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.)
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)
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.
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 differen-tiation, 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.
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.
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.
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)
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)
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.
Cardiac myopathy is one of the oldest known physical consequences of high alcohol consumption. Similar to ethanol's effects on skeletal muscles, the cells of the heart muscle are damaged by ethanol's influence on ion channels and pumps etc. Atrophy leads to a dilatation of the heart as a whole.
Recently, the effect of alcohol on coronary heart disease has been widely discussed. Indeed, it seems that there is a beneficial effect of moderate alcohol consumption. Although the reasons are currently under discussion, recent data suggest, that the combination of several actions including changes in lipid metabolism, antioxidant effects, changes in haemostasis and platelet aggregation, arterial vasodilatation mediated by NO release and the expression of cardioprotective proteins contribute to these ‘French Paradox’.(34) It seems that an alcohol-induced increase in high-density lipoproteins and a decrease in low density lipoproteins may play a role in this process—an alteration in platelet aggregation could be one possible mechanism of action. Besides cardiomyopathy, cardiac arrhythmias are prominent consequences of alcohol consumption. Close to one-third of all cardiomyopathies can be attributed to alcohol consumption.
A dose-response relationship between drinking and diastolic and systolic blood pressure has been shown consistently.(31) In alcohol consuming population, the amount of alcohol consumption is significantly associated with hypertension and cardiovascular as well as all cause mortality. It is not clear, however, whether this relationship can only be seen above a threshold level of consumption.
There is very clear evidence that alcohol increases the risk of cancer at the upper bronchodigestive tract. This includes cancer of the mouth, pharynx, larynx, and oesophagus. Additionally, alcohol consumption correlates with primary liver cancer. A possible link between alcohol and breast cancer is still a matter of debate: the association is not strong and not necessarily causative, at least for moderate consumption.(35) The same seems to be true for the correlation between beer drinking and cancer of the rectum.
Schuckit, M.A. (2006). Drug and alcohol abuse: a clinical guide to diagnosis and treatment. Springer, Berlin.Find this resource:
Erickson, C. (2007). The science of addiction. From neurobiology to treatment. W.W. Norton & Company, New York.Find this resource:
Icon Health Publications. (2004). Alcohol addiction—a medical dictionary, bibliography, and annotated research guide to internet references. Icon Group International, San Diego.Find this resource:
1. Lishman, W.A. (1990). Organic psychiatry. The psychological consequences of cerebral disorder (2nd edn). Blackwell Science, Oxford.Find this resource:
2. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th edn). American Psychiatric Association, Washington, DC.Find this resource:
3. Glass, I.B. (1989). Alcohol hallucinosis: a psychiatric enigma-2. Follow-up studies. British Journal of Addiction, 84, 151–64.Find this resource:
4. Brown, S.A. and Schuckit, M.A. (1988). Changes in depression among abstinent alcoholics. Journal of Studies on Alcohol, 49, 412–17.Find this resource:
5. Stetter, F., Rein, W., and Mann, K. (1991). How depressive are male alcoholic inpatients? Psychometric results from the Tübinger Alkoholismusprojekt. European Psychiatry, 6, 243–9.Find this resource:
6. Kessler, R.C., McGonagle, K.A., Zhao, S., et al. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Archives of General Psychiatry, 51, 8–19.Find this resource:
7. Merikangas, K.R. and Angst, J. (1995). Comorbidity and social phobia: evidence from clinical, epidemiologic, and genetic studies. European Archives of Psychiatry and Clinical Neuroscience, 244, 297–303.Find this resource:
8. Kushner, M.G., Sher, K.J., and Beitman, B.D. (1990). The relation between alcohol problems and the anxiety disorders. American Journal of Psychiatry, 147, 685–95.Find this resource:
9. Schuckit, M.A. and Hesselbrock, V. (1994). Alcohol dependence and anxiety disorders: what is the relationship? American Journal of Psychiatry, 151, 1723–34.Find this resource:
10. Merikangas, K.R., Stevens, D., Fenton, B., et al. (1996). Comorbidity and co-transmission of anxiety disorders and alcoholism: results of the Yale Family Study. In Proceedings of the American Psychiatric Association, May 1996. American Psychiatric Association, Washington, DC.Find this resource:
11. Maier, W., Minges, J., and Lichtermann, D. (1993). Alcoholism and panic disorder: co-occurrence and co-transmission in families. European Archives of Psychiatry and Clinical Neuroscience, 243, 205–11.Find this resource:
12. Kendler, K.S., Walters, E.E., Neale, M.C., et al. (1995). The structure of genetic and environmental risk factors for six major psychiatric disorders in women: phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism. Archives of General Psychiatry, 52, 374–83.Find this resource:
13. de la Monte, S.M. (1988). Disproportionate atrophy of cerebral white matter in chronic alcoholics. Archives of Neurology, 45, 990–2.Find this resource:
14. Harper, C. (2007). The neurotoxicity of alcohol. Human & Experimental Toxicology, 26, 251–7.Find this resource:
15. Harper, C., Kril, J., and Daly, J. (1987). Are we drinking our neurons away? British Medical Journal, 294, 534–6.Find this resource:
16. Harper, C.G. and Kril, J.J. (1989). Patterns of neuronal loss in the cerebral cortex in chronic alcoholic patients. Journal of Neurology Sciences, 92, 81–9.Find this resource:
17. Ferrer, I., Fabregues, I., Rairiz, J., et al. (1986). Decreased numbers of dendritic spines on cortical pyramidal neurons in human chronic alcoholism. Neuroscience Letters, 69, 115–19.Find this resource:
18. Torvik, A., Lindbö, C.F., and Rodge, S. (1982). Brain lesions in alcoholics. Journal of Neurological Sciences, 56, 233–48.Find this resource:
19. Torvik, A. and Torp, S. (1986). The prevalence of alcoholic cerebellar atrophy. A morphometric and histological study of an autopsy material. Journal of Neurological Sciences, 75, 43–51.Find this resource:
20. Riley, J.N. and Walker, D.W. (1978). Morphological alterations in hippocampus after long term alcohol consumption in mice. Science, 201, 646–8.Find this resource:
21. Mann, K. (1992). Alkohol und Gehirn—über strukturelle und funktionelle veränderungen nach erfolgreicher therapie. Springer, Berlin.Find this resource:
22. Mann, K., Mundle, G., Strayle, M., et al. (1995). Neuroimaging in alcoholism: CT and MRI results and clinical correlates. Journal of Neural Transmission (General Section), 99, 145–55.Find this resource:
23. Charness, M. (1993). Brain lesions in alcoholics. Alcoholism, Clinical and Experimental Research, 17, 2–11.Find this resource:
24. Lemoine, P., Harousseau, H., Borteyru, J.-P., et al. (1968). Les enfants de parents alcooliques: anomalies observées à propos de 127 cas. Ouest Médical, 25, 477–82.Find this resource:
25. Dow, K.E. and Riopelle, R.J. (1985). Ethanol neurotoxicity: effects on neurite formation and neurotrophic factor production in vitro. Science, 228, 591–3.Find this resource:
26. Manning, M.A. and Eugene Hoyme, H. (2007). Fetal alcohol spectrum disorders: a practical clinical approach to diagnosis. Neuroscience and Biobehavioral Reviews, 31, 230–8.Find this resource:
27. Kumada, T., Jiang, Y., Cameron, D.B., et al. (2007). How does alcohol impair neuronal migration? Journal of Neuroscience Research, 85, 465–70.Find this resource:
28. Estruch, R. (1996). Alcohol and nutrition. In Alcohol misuse: a European perspective (ed. T.J. Peters), pp. 41–61. Harwood Academic, London.Find this resource:
29. Urbano-Márquez, A. and Fernández-Solà, J. (1996). Musculo-skeletal problems in alcohol abuse. In Alcohol misuse: a European perspective (ed. T.J. Peters), pp. 123–44. Harwood Academic, London.Find this resource:
30. Lieber, C.S. (1998). Hepatic and other medical disorders of alcoholism: from pathogenesis to treatment. Journal of Studies on Alcohol, 59, 9–25.Find this resource:
31. Huntgeburth, M., Ten Freyhaus, H., and Rosenkrank, S. (2005). Alcohol consumption and hypertension. Current Hypertension Reports, 7, 180–5.Find this resource:
32. Niebergall-Roth, E., Harder, H., and Singer, M.V. (1998). A review: acute and chronic effects of ethanol and alcoholic beverages on the pancreatic exocrine secretion in vivo and in vitro. Alcoholism, Clinical and Experimental Research, 22, 1570–83.Find this resource:
33. Higgins, E.M. (1996). Alcohol misuse and the skin. In Alcohol misuse. A European perspective (ed. T.J. Peters), pp. 77–87. Harwood Academic, London.Find this resource:
34. Providencia, R. (2006). Cardiovascular protection from alcoholic drinks: scientific basis of the French Paradox. Revista Portuguesa de Cardiologia, 25, 1043–58.Find this resource:
35. Poschl, G. and Seitz, H.K. (2004). Alcohol and cancer. Alcohol & Alcoholism, 39, 155–65.Find this resource: