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Genetics

The glass and lipstick

Alteration in a gene may make women 2.6 times more susceptible to alcoholism

EDUARDO CESARA risky quest for happiness: dependence equivalent to that caused by cocaineEDUARDO CESAR

For several years, science has been trying to establish the exact weight of environmental conditions and genetic heritage in the development of a series of psychiatric diseases, among which alcoholism. Determining with precision all the causes that drive some members of a population towards the uncurbed consumption of fermented and distilled beverages, while the others remain abstemious or moderate users, is perhaps an impossible task. Even so, a team of researchers from the University of São Paulo (USP) believes it has identified a genetic alteration that seems to increase 2.6 times the risk of Brazilian women exposed to alcohol to become dependent on it.

It is a variation in a stretch of the Maoa gene that can reduce the production of the type A monoamine oxidase enzyme. This protein acts on some chemical messengers of the brain – the so-called neurotransmitters, among which dopamine and serotonine -, responsible for communication between neurons and involved in regulating behavioral states, such as moods and aggressiveness. Identifying the genes that predispose towards alcoholism may help in the prevention of this dependence: a person who discovers that he has a greater propensity to the frequent consumption of alcohol can try to avoid contact with this kind of drink.

According to the study, which should be published shortly in Psychiatrics Genetics, women who show this alteration in at least one of the two copies of the gene – located in the X chromosome – synthesize from two to ten times less enzyme than normal, and may be more susceptible to developing alcoholism. “We cannot yet state categorically that this relationship really does exist”, ponders Mayana Zatz, the coordinator of USP’s Center for Study of the Human Genome and the leader of the team that did the work. “But there is a strong indication that a biological component may favor the occurrence of alcoholism among Brazilian women.” In men, who carry just a replica of the gene, a less functional version of Maoa would not increase their chances of becoming an alcoholic.

“Perhaps the genetic influence in favor of alcoholism is greater in the female sex than in the male sex, which suffers less stimuli in this direction in the environment”, comments Sandra Scivoleto, the coordinator of the Interdisciplinary Group for Alcohol and Drug Studies (Grea), linked to USP’s Psychiatry Institute, and one of those collaborating with the study. The Brazilian scientific article is not the first to point to a relationship between the Maoa gene and psychiatric disturbances or alcoholic or chemical dependence.

A German work, published in 2000 in the Journal of Neural Transmission, insinuated, for example, that the occurrence of alcoholism and antisocial behavior may be linked to a less functional version of this gene. However, the relationship was not proved in research done two years later with men from Finland. This gene recently made news for another reason. According to an article published in Science magazine of August 2 of last year, which analyzed the impact of alterations in Maoa in the male population of New Zealand, men who were mistreated in childhood and carried the less functional form of the gene had a greater chance of becoming violent adults. As it can be seen, Maoa is a frequent target for works on its impact on human behavior.

Four versions of the gene
To arrive at the conclusion that the least functional form of Maoa favors dependence on alcohol amongst Brazilian women, the scientists sequenced and analyzed the region that promotes this gene in alcoholics and in people not addicted to drink. This sequencing supplied information on the pattern of occurrence of a known segment of 30 base pairs (the chemical units that make up DNA) in this region of the gene. At the end of the work, the team from USP saw that the gene could be shown in four distinct forms, both in those dependent on alcohol and in healthy individuals. There were versions of Maoa, technical called alleles, with two, three, four or five repetitions of the stretch of 30 base pairs.

With this data to hand, the next step was to see if any of these alleles was associated with a propensity towards alcoholism. In order to facilitate comparisons, the patients and the individuals from the control groups were classified in two categories, according o their types of alleles. Those who had at least one copy of the Maoa with three repetitions of the genes in question – precisely the variant of the gene that produces less enzyme than normal – fell into one category. People with the other variations of the gene (two, four or five repetitions of the stretch of 30 base pairs) made up the other group.

When the sums had been done, the researchers found that 62% of the alcoholic women carried at least one allele that reduced the synthesis of monoamine oxidase. Amongst those who were not dependent on drink, and were part of the control group, this level fell to 38%. The prevalence of the version of the Maoa gene that lowers the production of the enzyme was 45% in alcoholic men and 31% in healthy persons. “In males, contrary to what happened with women, this difference was not significant from the statistical point of view”, comments Camila Guindalini, who is studying for her doctorate at USP’s Biosciences Institute, and is one of the authors of the study. “That is why we cannot, for the time being, suggest that variations in the Maoa gene may be linked to the occurrence of alcoholism in Brazilian men.”

The claims by the team from USP – which describes Maoa as a probable gene of risk for alcoholism amongst Brazilian women, but never as the cause of this disorder – are cautious for two reasons. The first, more of a methodological nature, concerns the modest size of the group analyzed. The sample of alcoholics was made up of 93 patients (52 men and 41 women, about 45 years old) who were undergoing treatment at Grea. Made up of people who were not dependent on alcohol, the control group had the same number of individuals, of a similar age and ethnic origin as those of their peers addicted to fermented and distilled beverages. “We had a lot of difficulty in finding and convincing women who were dependent on alcohol to take part in the study”, says Mayana. “If 300 alcoholics had taken part in our work, we could be more certain of the role of the Maoa gene in unleashing this disease amongst women. We need more volunteers to carry on with the researches.”

The second reason that justifies moderation is of a more general order. In spite of there almost being a consensus in the scientific area that alcoholism has both biological and behavioral components at its root, it is not at all easy to draw the line where the influence of the genes ends and the influence of the environment begins. This difficulty is even greater in societies that stimulate the consumption of alcohol among persons of both sexes and transform the act of drinking beer, wine or any other drink into a cultural trait.

In Brazil, the number of women alcoholic is four times smaller than those of the male sex. Moreover, drinking is a cultural habit that is not much stimulated amongst women. For this reason, according to Mayana, the weight of the genetic factors that predispose towards alcoholism must be greater – and more easily identifiable – in Brazilian women than among men in Brazil, or even than in the female population in Europe or the United States, social groups in which the presence of abstemiousness is more of a rarity. “This is our working hypothesis”, comments the coordinator of USP’s Center for Studies of the Human Genome, one of the ten Research, Innovation and Diffusion Centers (Cepids) created by FAPESP in 2000. For the while, the first results of the study of the Maoa gene are confirming this hypothesis.

Gambling addicts than alcohol

When that uncontrollable desire strikes to fill the glass or to spend all the money on a bet, who has the greater difficulty of staying away from his vice, the alcoholic or the pathological gambler? Psychiatrist Hermano Tavares, the coordinator of the Pathological Gambling Clinic (Amjo), of the Univeristy of São Paulo’s Psychiatry Institute, has concluded that the compulsion felt by the compulsive better is of a magnitude 50% greater than the one experienced by the alcoholic. Compulsion is that morbid desire that leads dependents to backslide into their vice, despite knowing its negative effects.

The chains that bind the gambler to games of chance are so strong that the physician compares this dependency to the one experienced by those who are addicted to chemical drugs. “Instead of resembling an alcoholic, the pathological gambler behaves in a way that is closer to that of a cocaine addict”, explains the doctor, who, with the assistance of tests and questionnaires, compared the personality of 40 drink addicts with 40 electronic bingo addicts, half from each sex. The study was done with patients from the psychiatry service of the University of Calgary, in Canada, where the physician completed his postdoctoral course at the end of 2002. “But the conclusions are valid for pathological gamblers from any country”, says Tavares.

One marked difference between the alcoholic and the gambling addict: while the former does not find any positive emotions in anything – except for cards, roulette and bingo cards -, the latter alleviates his negative sensations with the help of drink. The pathological gambler makes his bets to try to be happy. “Nothing gives him as much fun as gambling”, the psychiatrist avers. The alcoholic drinks to forget his sorrows. “He is a type that is more vulnerable to depression”, Tavares comments. Another contrast relates to the rhythm with which each one of these dependents feeds his vice. The alcoholic usually drinks with a regular consistency, as if he were following a ritual or putting into practice an almost commonplace habit. It is not rare for him to drink the same dose of alcohol every day, at the usual time. “The pathological gambler, like the cocaine addict, acts on impulse”, Tavares likens. When he has funds to hand to gamble, he bets all his money in a single day. He only stops when he goes bust financially, which leads him to a physical and mental breakdown. “The same thing happens with cocaine addicts”, explains the doctor.

The after-bankruptcy of the pathological gambler is also similar to the recovery period of the cocaine addict. Both spend days cursing their dependence, promising themselves that they will not repeat the error. Until the irresistible desire strikes again, in the case of one, to gamble, and to snort, in the other case. At these times, if they do not have any more money, the pathological gambler (or cocaine addict) does anything to finance his vice: he steals, sells household objects or other people’s. The unbridled gambler lies to others (and to himself), and says that he is going to bet just one more time. And that, this time, he is going to recover all the money he has lost on other occasions. “He loses again and is once again physically and mentally exhausted”, says Tavares. The cycle of dependence then restarts.

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