ALCOHOLISM: A DISEASE

In 1956 the American Medical Association decided that alcoholism is a disease, however more than 30 years later this is still debated in certain circles. Besides the medical opinion, there are many others (e.g., legal, sociological, religious) which derive from any number of social pressures. For example, the Supreme Court recently decided that the Veteran's Administration could consider alcoholism an individual choice rather than a disease. This decision, in many peoples' opinion, was made because of the financial implication related to "Service-connected Disability" payments rather than the merits, or lack thereof, of alcoholism as a disease. This in only one example of of the many biased opinions (including the medical one) on whether or not alcoholism is a disease.

What does support the concept of alcoholism as a disease? There is an abundance of information. Alcoholism is often compared to diabetes. Most people are able to eat carbohydrates and metabolize them without difficulty, however this is not the case with people who have diabetes mellitus. Many years ago, we had no idea why people with diabetes got into metabolic difficulty but now we know that it is because of an intrinsic lack of insulin and that this is genetically determined. There is a list of progressive symptoms related to diabetes: polyuria, polydipsia, weight loss, blurred vision, and nausea and vomiting are seen acutely. If the disease goes on untreated, then there is end organ failure disease goes on untreated, then there is end organ failure and patients with diabetes develop failure of their vision and kidneys as well as significant cardiovascular disease with heart attack and stroke. How does one treat this problem? The patient needs insulin and a very controlled lifestyle diet, exercise and very special attention to one's habits. This will at least slow down the progression of the disease.

The same concepts of "disease" apply to alcoholism, and the progression of the disease was defined by Jellinek and is shown on the attached was defined by Jellinek and is shown on the attached Jellinek chart. Alcoholism is a progressive and terminal disease if no intervention occurs. It is clear that alcoholism fits the definition of a disease, and there is additional supportive evidence of this concept based on recent research and literature.

GENETICS AND BIOLOGIC MARKERS OF ALCOHOLISM

Over the past few years investigators have invested a great deal of time, energy and finances into acquiring support for the idea that alcoholism may be a biologically determined disease. There would be many implications of such a discovery not the least of which might be treatment which is more effective than those currently available. As has been the recent tradition in Biologic Psychiatry, many of these investigations have concerned the genetics of these investigations have concerned the genetics of alcoholism-if the illness is determined to be inherited, then there must be a biologic component to the illness which is encoded in one's deoxyribonucleic acid (DNA). The other primary avenue of study has been to look for biologic differences between alcoholics and to look for biologic differences between alcoholics and their family members and normals. From this investigation we have derived a number of "biologic markers" of alcoholism. Unfortunately, we are still in the embryonic stage of this work, and there are no markers with adequate sensitivity and specificity to predict there are no markers with adequate sensitivity and specificity to predict who will and who will not be alcoholic.

GENETIC STUDIES

There have been numerous genetic studies published over the past several years. Many of these have been Scandinavian because of the meticulous record- keeping which is done in Denmark. However recently, a number of studies have been conducted in the U.S. Marc Schuckit, M.D. has been one of the primary investigators in this area. His studies indicate that the offspring from two alcoholic biologic parents are four to eight times as likely to develop alcoholism as the general population. This is a strong indicator that there is a heritable trait for alcoholism. The challenge about this type of research often comes in the form of a question about the social/environmental influence of having two alcoholic parents. That is, is the increased likelihood of developing alcoholism due to the biology or to the fact that these children grew up in a home with two alcoholic parents? How can this be studied? Dr. Remi Cadoret at the University of Iowa published an elegant study in the Archives of General Psychiatry in December of 1986 which examined this issue carefully.

Dr. Cadoret's study examined 443 adoptees-infants adopted out of their biologic families at birth. This provides the opportunity to examine both biologic and birth. This provides the opportunity to examine both biologic and environmental effects on the incidence of alcoholism in the offspring. In addition, he was able to examine other factors which might correlate with the development of alcoholism as well. This study led to a number of interesting findings.

1. There was a genetic influence on the development of

alcoholism--children born to alcoholic parents and reared by

non-alcoholic parents developed alcoholism at the rate predicted by the

other genetic studies.

2. Having alcoholic parents also predicted the development of drug

addiction (other than alcoholism).

3. Parents who were addicted, predisposed their biologic offspring to

developing drug addiction and/or alcoholism.

4. Antisocial personality traits seemed to be inherited and to be

biologically associated with drug addiction.

5. Developmental trauma to children not genetically predisposed to the

development of chemical dependency increased the incidence of

development of the disease.

This study clearly separated the biologic and environmental influences on the incidence of alcoholism. In addition, it suggested that alcoholism and other drug addictions may not be different from each other-an idea that many treatment clinicians have suspected for a long time. The study did not discount the idea that developmental experiences may be of importance. Interestingly, the study demonstrated statistical evidence for heritability of what has traditionally been considered to be environmentally determined-personality style (or disorder)

Other investigators who have contributed greatly to the field of genetics of alcoholism are Kaij, Kaprio, Goodwin, Schulsinger, Winokur, Guze and Cloninger.

BIOLOGIC MARKERS

There have been numerous studies over the past several years looking for specific biologic markers of alcoholism. The idea has been that a biologic marker which is associated with alcoholism will give validity to the disease concept, aid in the diagnosis of the disease and, perhaps, lead to more specific treatments with better outcomes. Although numerous biologic markers have been found, no marker to date has a high sensitivity or specificity and there has been no etiologic association made with any such marker. Despite the disappointing results so far, this line of research is absolutely necessary if we are to improve our understanding of the disease and search for better treatments. There have been no definite cause and effect sequences defined at this point, but the following examples of biologic markers still remain supportive evidence for the concept of alcoholism being a biologic disease.

Tetrahydroisoquinolone (THIQ)- This compound is a condensation product which has been found in the urine of some alcoholics but not in non-alcoholics (or in smaller quantities). THIQ has been found to bind to the delta opioid receptors in the central nervous system and seems to make mice prefer ethanol. The suggestion has been made that this may explain the addiction to alcohol, but this is largely unsupported.

Thyrotropin Releasing Hormone (TRH) Stimulating Test- This test evaluates the function of the hypothalamic-pituitary-thyroid axis. It is used primarily to diagnose diseases of the thyroid gland. Marku Linnoila at the NIAAA has studied this test in alcoholics and their children and found that sons of alcoholic fathers have an abnormal TRH test but daughters do not. He found that these sons (even without phenotypic alcoholism) demonstrated an increase in baseline phenotypic alcoholism) demonstrated an increase in baseline thyrotropin and peak thyrotropin levels after stimulation as compared to the controls.

Alcohol Dehydrogenase and Acetaldehyde Dehydrogenase- These are normal enzymes in the liver which metabolize alcohol to harmless metabolic intermediates. [ethanol is metabolized to acetaldehyde (very toxic substance) by alcohol dehydrogenase and the acetaldehyde is metabolized to acetic acid by acetaldehyde dehydrogenase] There are racial differences in the form of these enzymes. Asians and American Indians have atypical forms of these enzymes (called isoenzymes) have atypical forms of these enzymes (called isoenzymes) such that alcohol is metabolized more rapidly to acetaldehyde and acetaldehyde is metabolized less rapidly to acetic acid. Four percent of the Swiss have been found to possess the atypical ADH isoenzyme whereas 89% of Chinese and 85% of Japanese have atypical aldehyde dehydrogenase. This interesting research was derived from the early investigations of facial flushing among various races. It was noted that approximately 10% of Caucasians experienced facial flushing with acute ingestion facial flushing with acute ingestion of alcohol whereas many more Asians and American Indians had this response. The degree of facial flushing was correlated directly with the concentration of acetaldehyde in breath or blood.

Platelet Monoamine Oxidase (MAO) and Platelet Adenylate Cyclase- Boris Tabakoff and his colleagues at the NIAAA have found that alcoholics do not have different levels of these enzymes on their platelets, but that alcoholics have a different degree of inducibility than normal controls. This is a phenomenon which persists after discontinuation of drinking, however it is not certain at this point whether the abnormal enzyme activities are present prior to the beginning of drinking (i.e., a marker for the development of phenotypic alcoholism) or are a result of exposure to alcohol (i.e., an effect of alcohol). A prospective study needs to be conducted in order to determine this.

[33;1m                       Progression of Alcohol/Drug Dependency[37;0m
(based on Jellinek chart)
[36;1m                                    Early Stage[37;0m

Drinking to calm nerves Uncomfortable situation where there is no alcohol/drugs Increase in alcohol tolerance Driving while under the influence Desire to continue drinking/using when others stop Relief drinking commences Secret irritation when your drinking/using is discussed Occasional memory lapses after heavy drinking/using Preoccupation with alcohol/drugs (thinking about next drink/drug) Lying about drinking Increasing frequency of relief drinking/using Loss of control phase -- rationalization begins Hiding liquor/drugs; sneaking drinks/drugs Meals missed due to drinking/using

[36;1m                                   Middle Stage[37;0m

Increasing dependence on alcohol/drugs Preoccupation with drinking/drugging activities Drinking/using bolstered with excuses Feeling guilty about drinking/using Irritability when drinking/using is discussed Tremors and early morning drinks/drugs Avoid non-drinking/non-using situations Dishonesty in non-drinking/using activities Increased memory blackouts Loss of other interest/unable to discuss problems Promises and resolutions fail repeatedly Grandiose and aggressive behavior Neglect of food/controlled drinking/using fails Family, work, money problems Family and friends avoided; drinking/using alone (secretly) Possible job loss

[36;1m                                     Late Stage[37;0m

Radical Deterioration of family relationships Now thinks: "responsibilities interfere with my drinking/using" Physical and moral deterioration Unreasonable resentments Loss of "will power" and onset of lengthy drunks/highs Urgent need for morning drink/drug Geographical escape attempted Persistent remorse Impaired thinking and memory loss Successive Lengthy Drunks/highs Loss of family Decrease in alcohol/drug tolerance Hospital/sanitarium Undefinable fears Unable to initiate action; extreme indecisiveness All alibis exhausted Unable to work; obsession with drinking/using Complete abandonment: "I don't care" Continued Deterioration

[36;1m                             Progression of Recovery[37;0m

Institutionalization or death Calls for help Meets recovering alcoholics/addicts: a ray of hope Learns alcoholism/addiction is a disease Medical help drying out Expresses desire for help Group therapy Starts to react to help from other alcoholics/addicts Pride in appearance is renewed Realizes alcoholism/addiction can be arrested Begins to get honest with self Spiritual needs examined Dawn of new hope Belief that a new life is possible Interest in group therapy and others grows Spiritual values develop Thinking becomes more realistic Natural rest/sleep and appetite return Your family and friends notice change and growth Diminishing fears and anxieties Self esteem starts to return A new set of values develops - with honest training New circle of friends offer encouragement Readjustment of needs to self and family Future is faced with new positive attitudes New interests develop Increase in emotional stability Sense of financial responsibilities returns Rebirth of ideals Return of vocational confidence and quality Activities with others increases Contentment in sobriety unfolds A new appreciation of spiritual values Improved peace of mind Rationalizations recognized Increasing tolerance Recovery and sobriety continue Action is the magic word Working with others Recovery [1m^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ END OF FILE ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^[0m