Gender differences in alcohol use, abuse, and dependence are a consistent finding in the literature35
. A significantly higher proportion of the population of men in the UCSF sample reported drinking regularly between the ages of 19 and 35 years than women, and those participants who developed regular drinking at younger ages were significantly more likely to become alcohol dependent than those who chose to begin regular drinking at later ages. This effect was particularly significant between ages 15 and 25. These data are consistent with a number of previous studies that have provided data to suggest that individuals who drink before the age of 15 years are substantially more likely to become alcohol dependent31, 36–38
. The data from the UCSF study extends those findings and also demonstrated a cohort effect with the relatively younger women (<48 yrs) reporting a net decrease in the age of regular drinking that was twice as large (4 yrs) than that for men (2 yrs). These data confirm those published by Grucza and colleagues39
, using data from the NLAES and NESARC who also found that age of onset of drinking had decreased in the younger birth cohorts examined. Additionally, Grucza and colleagues39
, found that age of onset of drinking accounted for much of the increase in lifetime alcohol dependence among women.
Age at which a person first drank regularly was not found to be heritable in the population ascertained by the UCSF family study. These findings are consistent with data from Ehlers and colleagues31
who demonstrated that age at first intoxication was not heritable in a population of American Indians living on reservations. However, regular drinking in this study was not defined by a quantity and frequency measure. If regular drinking were defined differently, say as early problem drinking, it might have been found to be heritable. How environmental factors may influence the age at which a person first begins drinking regularly in such a way that leads to increased risk for alcohol dependence is not entirely clear. One hypothesis posits that early drinking disrupts the normal course of social and intellectual development leading to an increased risk for a number of social and psychological pathologies including drug addictions40, 41
. An alternate hypothesis has been forwarded, suggesting that drug addictions and psychopathology are in fact a reflection of a more general underlying susceptibility to psychopathologies and disinhibitory behavior42–45
. Although most studies point to “age of onset of regular drinking” as an environmental variable it may represent different constructs at different ages. For instance, very early onset of drinking (before the age of 13) may represent a more general measure of disinhibitory behavior or conduct disorder and as such could potentially be more heritable. In the present study the number of individuals with very early onset of drinking was limited and thus the statistical power for evaluation of the heritability of regular drinking in this age group was limited. As adolescence progresses, drinking becomes more common and may be highly influenced by such environmental variables such as peer pressure and social circumstances; whereas, individuals who have not drank regularly after the age of 21 may possess protective factors that may be both environmental (religion, family norms) or genetic (low tolerance to taste or effects of alcohol). Further studies are needed to disentangle the set of factors leading to regular drinking in adolescence.
A high degree of similarity was observed between men and women in the UCSF sample of alcohol dependents in many aspects of their clinical course. These data expand earlier findings from studies involving different subgroups of U.S. populations of alcoholics21, 22, 26–28, 46
. While men and women in the UCSF study had highly similar clinical courses a few differences were found in the proportion of women participants endorsing individual alcohol-related items when compared to men. As might be predicted, men endorsed more antisocial symptoms than women such as physical fights and arrests. However, women in the UCSF sample were just as likely as men to endorse severe alcohol dependence symptomatolgy such as withdrawal, psychological impairment, health problems, and continued drinking despite health problems or serious illness. The age at which women first reported alcohol-related events was approximately three years later than men, but while their overall clinical course progressed highly similarly there was evidence of “telescoping” or a shortening clinical course by approximately four years. These data are consistent with several other studies that have reported telescoping of the clinical course of alcoholism in women20, 28, 47
A high degree of similarity between UCSF Family Alcoholism Study participants and those participating in the COGA study in their clinical course was also found. However, COGA alcoholics reported alcohol-related life problems approximately three years earlier than the UCSF sample and alcohol dependent participants in the UCSF family study overall were significantly more likely to report alcohol-related life events than COGA participants. The only variable that was more frequent in the COGA sample was physical fights. Hill9
has suggested that the presence of fighting while intoxicated was the best discriminator of being an alcoholic from a family with a history of sociopathy. Gilligan and colleagues48
also suggested that fighting while drinking was associated with alcoholics who showed more antisocial behaviors. While ASPD was not directly assessed in the UCSF population these findings suggest that the UCSF study participants while endorsing a severe form of alcoholism with withdrawal and medical problems may have relatively less antisocial behaviors, such as fighting while intoxicated, than other large samples. These data also suggest that other risk factors most likely explain most of the genetic and environmental variance for the severe form of alcohol dependence seen in this sample, particularly in women. In this light, Hill9
has proposed a type III alcoholism that is not related to paternal sociopathy but still represents a severe form of the disorder.
Data from the UCSF study supports this idea that alcoholism in women can be significantly heritable and perhaps more heritable than in men, at least within this population. These data also support the conclusions of Hill35
who has questioned the notion that, in general, alcoholism in women may have less of a genetic diathesis in women. There have been conflicting data on estimates of heritability of alcohol dependence in women with some studies reporting negligible14
and others substantial18, 49
heritability. It has been suggested by Prescott and Kendler50
, that conflicting results between studies might in part be due to differences in sampling methods. If differences in alcoholism rates between men and women are in part due to environmental factors (such as sex specific social pressures to drink (or not to drink) during adolescence and young adulthood) then one would predict that women would actually have a more heritable form of the disorder. This hypothesis is consistent with the data obtained in the UCSF Family Study where the heritability estimates for women were higher than for men.
This study has several implications for clinical medicine and public health. That this and other studies have found that earlier ages of onset of regular drinking are associated with higher rates of lifetime alcohol dependence suggests that clinicians should be giving this information to parents of children under the age of 13 years so that parents are better able to monitor and intervene if drinking starts during their children’s teenage years. If most of the variance in early drinking is environmental, as suggested by this and other studies, transmitting that information to parents and communities is important because environmental interventions at both the family and the community levels may be effective in reducing underage drinking. Clearly, the environmental factors that lead to early regular drinking need to be identified and preventive measures aimed at those factors implemented by parents and communities. Additionally, the fact that alcohol dependence has been found to be heritable in women as well as in men suggests that it is important to tell family members of an alcohol dependent proband that they are at increased risk for the development of the disorder regardless of the gender of the proband or family member. Finally, the fact that a number of studies have demonstrated that alcohol dependence has a clear clinical course and that the order of appearance of specific symptoms appears to be invariant to ethnic heritage, gender, or clinical subtype, strengthens the disease construct of the disorder. It also suggests that clinicians can estimate where a patient is on his/her clinical course by evaluating what symptoms he/she is currently experiencing. That kind of estimate is useful not only for evaluating prognosis but for assessing when interventions of different intensities may be appropriate based on the likely near term progression of the disease. That information is also useful to patients and their families for motivating and planning treatment interventions earlier rather than later in the disease progression.
However, the results of this study should be interpreted in the context of several limitations. First, the findings may not generalize to other large samples of alcoholics that were ascertained without bias. Second, only retrospective and cross-sectional data on alcohol use and use disorders were assessed. Third, comparisons to other large samples may be limited by differences on a variety of variables including recruitment, as well as a number of genetic and environmentally determined variables. The family design cannot distinguish whether the causes of familial similarity are genetic or environmental in nature. Finally, this study was not designed to measure unbiased heritability of alcohol consumption related traits. However, because sampling from families was biased towards alcohol dependent family members the observed estimates are biased but this is not expected to affect the assessment of whether a sex specific heritability is greater than that of the other gender.