SUBSTANCE ABUSE. A MULTIDIMENSIONAL PROBLEM IN EVERY DAY CLINICAL PRACTICE II

ALCOHOL AND “SPECIAL POPULATIONS”: BIOLOGICAL VULNERABILITY I.A.LIAPPAS MD Associate Professor of Psychiatry Athens University Medical School Eginition Hospital-Psychiatric Clinic INTRODUCTION Alcohol has been consumed in most societies around the world since the dawn of recorded history. Most people who drink responsibly derive pleasure from their drinking and experience few adverse effects. However, for certain individuals or in certain circumstances, even low or moderate levels of alcohol may be problematic. For a large portion of these “special bold populations”, vulnerability is generally not psychological or due to social or economic conditions. Instead, a biological predisposition makes them especially susceptible. “SPECIAL POPULATIONS” It is important to distinguish between those with a biological vulnerability to alcohol, for whom even low amounts of alcohol may result in problems, and those at risk because of their heavy and chronic alcohol consumption. The risk factors for these two groups may be quite different, as are the implication for prevention, although there may also be areas of overlap. The term “special populations” has sometimes been applied to groups that fall into this higher risk category, reflecting the fact that, for the most part, advice on drinking given to populations at large may not apply them. Because of their vulnerability, these individuals should probably be concerned about the effects alcohol may have on them. BIOLOGICAL VULNERABILITY TO ALCOHOL Biological vulnerability to alcohol depends on several factors. The genetic makeup of an individual, general health status, or the presence of a particular medical condition may confer vulnerability to alcohol. Variables such as gender, race and age also play a role, all influencing the way in which ethanol is metabolized by the human body and the way in which it interacts with other biological functions. GENETICS I The general makeup of individuals is largely responsible for their vulnerability to alcohol. Genetic differences may underlie variation in how alcohol is metabolized, how the brain and neurotransmitter systems respond to alcohol, or the effects of alcohol on particular organs or conditions. The results of many studies suggest that variation in several genes may be involved, including those coding for the enzymes responsible for metabolizing alcohol and those coding for receptors to neurotransmitters responsible for how the brain responds to alcohol. In fact, a genetic component has been identified for a number of neurotransmitter systems (Begleiter et al. 1955, 1999, Eckert et al. 1998, Loh and Ball, 2000). GENETICS II TOLERANCE: For some populations, genetic vulnerability means low tolerance to alcohol and the inability to process it, while for others it is an increased risk for alcohol abuse or dependence. PHENOTYPE MARKERS: The genetic variations may also coincide with phenotype markers such as brain activity, and certain personality traits. Research has suggested that high tolerance to alcohol early in life may predict the development of dependence later in life.(Porjesz 1998, Soloff 2000, Schuckit and Smith 2001) FAMILIAL COMPONENT For individuals whose genetic makeup puts them at increased risk for alcohol abuse/dependence, it seems that there is a familial component to vulnerability, transmitted from one generation to the next. Data from America and Europe suggest that an estimated 5 to 10% of female relatives of alcoholics and 25% of male relatives will develop alcohol dependence themselves. (Goodwin 1985, Schukit et al. 2000). RACE Among some Asians, alcohol metabolism is impaired by a nonfunctional form of the enzyme aldehyde dehydrogenase (ALDH). In individuals who possess this deficiency, reactions to even small amounts of alcohol may be severe (facial flushing, nausea, heart palpitations and dizziness). Two subgroups exist among those affected-those with an inactive form of the enzyme (“fast flushers”), and those with a moderate inactivation of ALDH (“slow flushers”). Research suggests that roughly half of Chinese, Japanese, Koreans and other Asians are affected by this condition. It is possible that variations in the levels of enzyme activity may account for some differences in consumption patterns among racial and regional groups. (Wull et al. 2000, Goedde et al. 1992, Tsutsumi and Takada 1997,Shen et al. 1997, Gill et el. 1999, Chen et al. 1999). HEALTH STATUS I One of the main determinants of susceptibility to potential adverse effects of alcohol is health status. NUTRITION: It is a key factor in how alcohol affects the human body. Individuals who are malnourished are especially vulnerable. For example, thiamine deficiency most often seen in chronic alcohol abusers, has been linked with neurological impairment and conditions such as Wernicke-Korsakoff syndrome (Charness 1999). HEALTH CONDITIONS: For diabetics, even moderate alcohol consumption can induce low blood sugar levels, and the interaction between alcohol and diabetes medication can result in facial flushing, rapid heartbeat and dangerously low blood pressure (Weathermon and Crubb 1999). HEALTH STATUS II HYPERTENSION: As alcohol has the effect of increasing blood pressure, individuals with hypertension may be adversely affected by drinking (Beilin, 1995). HEPATITIS C: For those infected with hepatitis C, alcohol may accelerate the rate of liver damage increasing the risk of cirrhosis (Regev and Jeffers 1999). MEDICATIONS: Alcohol consumption may enhance the sedative effects of tricyclic antidepressants, sedative drugs and opioids. The anti-clotting effects of the anticoagulant warfarin may be altered by alcohol (Weathermon and Crabb 1999). GENDER One of the main influences in vulnerability to alcohol is gender. By virtue of their physiology, women are more susceptible than men to the effects of alcohol. A smaller blood volume and higher proportion of body fat mean that the effects of alcohol are felt at lower doses in women than they are in men (Thomasson,1995). Women and men also differ from each other in the way they metabolize alcohol. The activity of alcohol dehydrogenase (ADH), the other key enzyme involved in the breakdown of ethanol, is roughly 70-80% greater in men than it is in women (Lieber 2000). This difference diminishes in postmenopausal women, whose estrogen levels do not fluctuate with the menstrual cycle (Erricson, 1996). PREGNANCY Here, it is not so much the pregnant woman, but the developing fetus that may be placed at risk. The threshold at which vulnerability to alcohol begins has not been established (Allebeck and Olsen,1998). However, it is clear that the heavy chronic maternal drinking has effects on growth and development and, in severe cases, potentially it results in fetal alcohol effects (FAE) and syndrome (FAS) (Abel,1998). BREAST CANCER Research suggests that there may be some association between alcohol consumption and the risk for breast cancer, although the extent of this link and the role of other predisposing factors have not been determined (Katsouyanni,1994). Studies have indicated that a genetic component may be involved in any vulnerability for breast cancer that may be linked to alcohol consumption (Vachon et al,2000). AGE I ELDERLY: Another important factor in biological vulnerability to alcohol is age. It has been shown that the activity of the metabolizing enzyme ADH decreases with age, especially in men, increasing their susceptibility to the effects of ethanol (Seitz et al,1990). In addition, the elderly are more likely than younger people to suffer poor health and take medications, increasing their vulnerability for reasons addressed earlier. Changes in general metabolism in the elderly may also put them at increased risk (Koehler,2001). AGE II YOUNG: Biological vulnerability to alcohol is not limited to the elderly but may also be an issue for young people. Aside from the psychosocial aspects of alcohol abuse for children and youth, there is evidence that psysiological changes occuring in the developing brains of children may affect the way in which responses to alcohol are modulated (Spear,2000). CONCLUSIONS Biological vulnerability to alcohol is complex, involving as much the genetic blueprint of an individual as general health and other factors over which they may be little control. However, it is the interaction between these factors and the behaviors in which we, as individuals, engage that determines whether or not such a predisposition will result to harm. Much of the research on the effects of alcohol on these processes is derived from animal models and from experiments conducted in vitro. Consequently, some cautions is required when extrapolating these data to humans.