5
Etiology

Etiological research focuses primarily on the likely causes and correlates of drug use; it has identified many factors that affect drug use, although no single variable or set of variables explains drug use by an individual. There is no reason to believe that the same factor will affect all individuals in the same way, nor is there any reason to believe that the factors responsible for initiation of drug use are of equal importance in the continuation or escalation of use. Further, there appears to be no consensus as to what factors are involved in all cases of drug use and abuse (OTA, 1994). Generally, etiological studies conducted on population samples have focused on drug use; those conducted on clinical samples, especially those concerned with familial factors, have tended to focus on the etiology of drug abuse and dependence.

Two general categories of variables have been examined-risk factors and protective factors—although research, to date, has focused primarily on risk factors associated with drug use rather than on abuse and dependence. Risk factors are related to the probability of an individual's developing a disease or to vulnerability, which is a predisposition to a specific disease process (IOM, 1994b). Before a factor is labeled a risk factor, it has to satisfy the following conditions: the risk factor must be statistically associated with the disease; the risk factor must precede the onset of disease; and the observed association must not be spurious. There have been several recent reviews of the extensive literature on risk factors for drug use (see Newcomb and Bentler, 1986; Maddahian et al., 1988; Bry,



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Pathways of Addiction: Opportunities in Drug Abuse Research 5 Etiology Etiological research focuses primarily on the likely causes and correlates of drug use; it has identified many factors that affect drug use, although no single variable or set of variables explains drug use by an individual. There is no reason to believe that the same factor will affect all individuals in the same way, nor is there any reason to believe that the factors responsible for initiation of drug use are of equal importance in the continuation or escalation of use. Further, there appears to be no consensus as to what factors are involved in all cases of drug use and abuse (OTA, 1994). Generally, etiological studies conducted on population samples have focused on drug use; those conducted on clinical samples, especially those concerned with familial factors, have tended to focus on the etiology of drug abuse and dependence. Two general categories of variables have been examined-risk factors and protective factors—although research, to date, has focused primarily on risk factors associated with drug use rather than on abuse and dependence. Risk factors are related to the probability of an individual's developing a disease or to vulnerability, which is a predisposition to a specific disease process (IOM, 1994b). Before a factor is labeled a risk factor, it has to satisfy the following conditions: the risk factor must be statistically associated with the disease; the risk factor must precede the onset of disease; and the observed association must not be spurious. There have been several recent reviews of the extensive literature on risk factors for drug use (see Newcomb and Bentler, 1986; Maddahian et al., 1988; Bry,

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Pathways of Addiction: Opportunities in Drug Abuse Research 1989; Kumpfer, 1989; Brook and Brook, 1990; Swaim, 1991; Clayton, 1992; Glantz and Pickens, 1992; Hawkins et al., 1992; Petraitis et al., 1995). Protective factors are variables that are statistically associated with reduced likelihood of drug use (see Garmezy, 1983; Rutter, 1983; Brook et al., 1986a; Labouvie and McGee, 1986). In statistical terms, a protective factor moderates the relationship between a risk factor and drug use or abuse, or it buffers the impact of risk factors on the individual. When the protective factor is present, it is assumed that there will be considerably less drug use or abuse than would otherwise be expected, given the risk factors that are also present. Recent research has described two types of protective factors that could operate among adolescents (Brook et al., 1990). In the first type of protection (risk-protective), risk factors are attenuated by protective factors in the adolescent's personality. The second type of protection (protective-protective) involves a synergistic interaction whereby one protective factor potentiates the effects of another, so that their joint effect is greater than the sum of either protective factor considered alone. One of the goals of etiologic research has been to identify variables (such as risk and protective factors) that may be associated with drug use. The underlying interest in such variables is to determine if manipulation of risk and protective factors can moderate drug use outcomes. For either a risk factor or a protective factor to be targeted in intervention efforts, however, it is first necessary to demonstrate that the variable is amenable to manipulation and can be influenced by changes in the environment or by educational or medical interventions. Finally, intervention efforts must be carried out as well-controlled, rigorous experiments for the analysis of results to be meaningful. ACCOMPLISHMENTS Over the past 25 years, progress has been made in understanding risk factors associated with drug use, including biological, psychosocial, and contextual (social and environmental) risk factors. Unfortunately less is known about protective factors. The accomplishments noted below are representative of advances in the field and are not meant to document all risk factors or protective factors that have been identified. Finally, this chapter is not meant to be exhaustive, but to illustrate the types of studies that have illuminated knowledge in this field and to highlight opportunities for further study.

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Pathways of Addiction: Opportunities in Drug Abuse Research Biological Factors Genetic Vulnerability Family studies are important for identifying genetic vulnerability for drug abuse; for example, studies that have investigated generational differences in the transmission of drug abuse revealed that drug use or abuse is elevated among siblings of drug abusers and that there is a direct relationship between parental drug use or abuse and offspring use or abuse (Merikangas et al., 1992). A number of studies have focused on the familial aggregation of alcoholism and illicit drug abuse (see reviews by Merikangas, 1990; Glantz and Pickens, 1992; Gordon, 1994). Sons and daughters of alcoholics demonstrate a three- to fourfold risk of developing alcoholism (Cotton, 1979; Schuckit, 1986). Differences in the risk of alcohol and illicit drug use among individuals with a parental history of alcoholism may emerge at the time of transition from late adolescence to early adulthood, which may be a critical period for the expression of drug use vulnerability (Pandina and Johnson, 1989). The high recurrence of alcoholism among offspring of parents with alcoholism demonstrates that family history is one of the most potent predictors of vulnerability to alcohol abuse, which results to some extent from genetic factors (Merikangas, 1990; Pickens et al., 1991). However, the mechanism through which the family confers an increased risk is unknown. In addition to the contributions of genetic and biological factors to individual vulnerability for drug abuse, both transmitted and nontransmitted family factors, as well as unique environmental factors, appear to be involved in the vulnerability for drug abuse (Pickens et al., 1991). Family studies by themselves, however, cannot definitively determine the effect of genetics versus the environment on the development of alcoholism or drug abuse. Twin Studies A traditional study paradigm used to identify the role of genetic factors in the etiology of a trait or disorder is the study of twins. Typically, a comparison is made between the prevalence of a disorder among twin pairs who possess identical genes (monozygotic or identical twins) and twin pairs who have only half of their genes in common (dizygotic or fraternal twins). For any disease, if the environment has no influence, monozygotic twins would always be concordant (similar) with respect to the disease. However, because both genetic and environmental factors play a role, it is generally not possible to discriminate among the many possible influences. Additionally, monozygotic twins are often raised in similar environments (e.g., they are dressed alike, often share friends, and copy each other's behaviors) and often share environmental factors to a greater extent than dizygotic twins, which makes it difficult to

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Pathways of Addiction: Opportunities in Drug Abuse Research discriminate between genetic and environmental influences (Helzer and Burnam, 1991). Nonetheless, many twin studies have provided useful insight regarding the possible role that genetic factors play in the familial aggregation of drug abuse (Cloninger et al., 1981; Gurling et al., 1981; Hrubec and Omenn, 1981; Pedersen, 1981; Murray et al., 1983; Pickens et al., 1991). Cloninger and colleagues (1981) and others have found that monozygotic twins are about twice as likely as dizygotic twins (of the same sex) to be concordant for alcoholism. The highest twin correlations, however, were reported for nicotine and caffeine, based on a study of the Swedish twin registry (Pederson et al., 1981). The role of genetic factors in the etiology of drug abuse for monozygotic twins reared apart has been studied (Grove et al., 1990). Researchers examined the concordance for alcoholism, illicit drug abuse, and antisocial personality disorder among monozygotic twin pairs separated at birth and found that the heritability of illicit drug abuse exceeded that of alcoholism. Pickens and colleagues (1991) found that the drug abuse concordance rate was significantly greater for monozygotic twins than for dizygotic twins in males but not in females. Furthermore, illicit drug abuse has been found to be associated with conduct disorder in childhood and with antisocial personality in adulthood (see below). The aggregate of these findings suggests that genetic factors explain some of the variance in the development of drug abuse and that a large proportion of the heritability of drug abuse in adulthood may be attributed to genetic factors that underlie the development of behavior problems in childhood (Cadoret et al., 1980; Grove et al., 1990). Adoption Studies The optimal study paradigm for discriminating the interaction of genetic and environmental factors in the development of a trait or disorder is cross-adoption studies, in which adoptees with biological vulnerability for drug abuse, for example, are reared in homes of non-drug-abusing adoptive parents, and adoptees whose biological parents lack a history of drug abuse are reared in homes of parents with drug abuse. Cross-adoption studies of children of alcoholics who were raised by nonalcoholic adoptive parents have shown a three- to fourfold increased risk for alcohol abuse and dependence compared to adoptees whose parents were not alcoholics (Schuckit et al., 1972; Goodwin et al., 1973; Cadoret et al., 1980; Bohman et al., 1981; Cloninger et al., 1981). Physiological Vulnerability Review of the current state of knowledge of individual differences with regard to physiological effects of illicit drugs is beyond the scope of this chapter. However, such differences (see Chapter 3) are expected to

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Pathways of Addiction: Opportunities in Drug Abuse Research be key factors in the formulation of theories regarding the etiology of drug abuse. Physiological influences that may exacerbate an individual's vulnerability to drug abuse could include neurochemical system impairment and heightened susceptibility to a drug because of biologically determined responsiveness. Although there has been substantial research on individual differences in response to ethanol and nicotine, less is known regarding the effects of the major classes of illicit drugs of abuse, such as opioids, stimulants, and cannabis. Metabolic Variations There are large interindividual and interethnic variations in the outcome of alcohol use and abuse (Goedde et al., 1992). Studies have demonstrated that, in contrast to Caucasians, many Asians are biologically protected from becoming alcoholics because of the polymorphism of two liver enzymes: aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase-2 (ADH2). The Asians appear to have a protective factor in the form of inactive ALDH2 and high frequencies of atypical ADH2 (Higuchi et al., 1995), whereas Caucasians primarily have only active ALDH2 and usual ADH2 (Yoshida et al., 1991). The inactive form of ALDH2 is considered protective against alcoholism because it allows high levels of acetaldehyde to accumulate in the blood and causes adverse reactions, known as the flushing response (Thomasson et al., 1991; Yoshida et al., 1991). This increase in acetaldehyde blood levels after ingestion of ethanol appears to have a protective influence on further ingestion and thus appears to lower the rate of alcoholism (Bosron and Li, 1986). Efficient ethanol metabolism may enhance the risk of alcoholism by allowing ingestion of a sufficient quantity to mediate the addictive potential of alcohol. Studies of the male offspring of alcoholics have demonstrated that the ability to tolerate large quantities of alcohol with fewer subjective effects may be a potent signal of the subsequent development of alcoholism (Schuckit, 1984, 1985). Thus, the inability to metabolize a drug may be a protective influence in continued exposure, whereas efficient metabolism may permit high levels of exposure conducive to the development of abuse and dependence. Biochemical Markers Monoamine oxidase (MAO) is a widely studied biochemical marker for alcohol abuse. Several studies comparing alcoholics with nonalcoholics have found decreased platelet MAO activity levels among alcohol abusers (von Knorring et al., 1985; Pandey et al., 1988; Tabakoff et al., 1988). MAO is an enzyme that is important in the metabolism of a variety of brain neurotransmitters that affect behavior, including dopamine, norepinephrine, and serotonin. Although other biochemical markers have been investigated, no consistent findings have emerged.

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Pathways of Addiction: Opportunities in Drug Abuse Research Psychosocial Factors The majority of studies of psychosocial risk factors focus on adolescents and the initiation of drug use, rather than on the risk of escalating to abuse or dependence. Unfortunately, many of the studies are cross sectional, so that it is difficult to disentangle the risk factors for use from those for abuse and dependence. Additionally, many of these studies fail to control for parental alcoholism, psychiatric disorders, or other risk factors, and many of them do not distinguish between use and abuse. Given those limitations, a selection of studies that demonstrate risk factors contributing to psychological vulnerability for drug use is presented below. Personality Traits There is a substantial literature regarding the relationship between personality traits and drug use, particularly in adolescents (Jessor et al., 1973; Jessor and Jessor, 1975; Kandel, 1980; Hawkins et al., 1985; Brook and Brook, 1990; Clayton, 1992). Relatively few studies, however, have examined the specific role of personality traits in the development of drug abuse and dependence. The majority of studies have focused on the characteristics of alcoholics (McCord and McCord, 1960; Robins, 1966; Vaillant and Milofsky, 1982; Cloninger et al., 1988; Tarter et al., 1990). For example, the landmark studies of McCord and McCord (1960) and Robins (1966) revealed that alcoholism in adulthood was associated with antisocial behavior and aggressivity in childhood. Aggressive behavior in the first grade has been found to predict heavy alcohol use in late adolescence (Kellam et al., 1983). The onset of drinking is signaled by several antecedent personality attributes reflecting lower levels of conventionality, for example, lower values on academic achievement (Jessor and Jessor, 1975; Brook et al., 1986a), lower expectations of academic achievement (Jessor et al., 1972; Jessor and Jessor, 1975), more tolerant attitudes toward deviant behavior (Jessor and Jessor, 1975; Brook et al., 1986a), lower levels of religiosity (Jessor and Jessor, 1975; Webb et al., 1991), less of an orientation to hard work (Brook et al., 1986a), greater rebelliousness (Brook et al., 1986a), rejection of parental authority (Webb et al., 1991), fewer reasons for not drinking or less negative beliefs about the harmfulness of drinking (Jessor et al., 1972; Jessor and Jessor, 1975; Margulies et al., 1977), and greater positive expectancies about the social benefits of drinking (Christiansen et al., 1989; Smith and Goldman, 1994). Studies of the association between adolescent personality characteristics and illicit drug use found that many of the characteristics that

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Pathways of Addiction: Opportunities in Drug Abuse Research signaled the onset of drinking also predicted drug use. The most powerful predictors of more frequent drug use are the unconventionality variables, including rebelliousness, tolerance of deviance, and low school achievement (Brook et al., 1986a). Similar antecedent personality attributes reflecting lower levels of conventionality and more positive attitudes toward drug use predict the initiation of smoking, drinking, and drug use (Chassin et al., 1984; Krohn et al., 1985; Skinner et al., 1985; Mittelmark et al., 1987). In general, adolescents who start to use marijuana are less conventional in their attitudes and values and have weaker bonds to the conventional institutions of school and religion. This is shown in more tolerant attitudes toward deviance (Jessor et al., 1973; Brook et al., 1980), lower religiosity (Jessor et al., 1973), greater rebelliousness and lower obedience (Smith and Fogg, 1979), lower educational expectations (Brook et al., 1980), greater opposition to authority (Pederson, 1990), and more favorable beliefs about marijuana use (Jessor et al., 1973; Kandel and Andrews, 1987). Psychopathology Adult deviant behavior and antisocial behavioral patterns are often preceded by problem behaviors (i.e., rejection of societal rules, goals, and values) in late childhood and early adolescence (Jessor and Jessor, 1977; Robins, 1978). These behaviors coupled with increasing life stresses appear to be risk factors for drug abuse. Conduct disorder has been shown to precede the onset of drug abuse in several studies (Robins, 1966; McCord, 1981; August et al., 1983; Gittelman et al., 1985; Boyle et al., 1992) and to occur conjointly with drug abuse in others (Loeber, 1982; Lilienfeld and Waldman, 1990; Loeber et al., 1995). A prospective longitudinal study by Boyle and colleagues (1992) revealed that an earlier diagnosis of conduct disorder indicated greater risk for the initiation of marijuana and other illicit drug use four years later. It should be noted, however, that the majority of children with problem behaviors or conduct disorders do not become antisocial or drug-abusing adults. Although studies have observed that early antisocial behaviors and deviance are risk factors for drug abuse (Robins, 1966; Elliott et al., 1985; Kaplan et al., 1986; Robins and McEvoy, 1990), the two most common psychopathologies that have been identified repeatedly are depression and antisocial personality (Cadoret et al., 1980; Alterman et al., 1985; Deykin et al., 1987; Block et al., 1988; Muntaner et al., 1989; Grove et al., 1990). Studies of clinical and epidemiological samples also have suggested that drug abuse and psychopathology are often linked (Merikangas et al., 1994; Kessler et al., 1996). Inpatient and outpatient surveys reveal that

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Pathways of Addiction: Opportunities in Drug Abuse Research approximately one-third of patients in treatment for psychiatric disorders are drug abusers (Crowley et al., 1974; Fischer et al., 1975; Davis, 1984; Eisen et al., 1987). In these samples, disorders that have been associated with increased risk of alcoholism and drug abuse include conduct and oppositional disorders, especially those manifesting antisocial behavior; attention deficit disorder; and the anxiety disorders, particularly phobic disorders and depression (Weiss et al., 1988; Fergusson et al., 1994; Riggs et al., 1995; Kessler et al., 1996). The commonality of findings across these studies and samples further supports the results, in particular the studies of treated samples, delinquents, general population samples, and samples of different ages, such as adolescents (Riggs et al., 1995) or adults (Kessler et al., 1996). Additionally, a number of reports have shown a high incidence of drug abuse in psychiatric patients (Galanter and Castaneda, 1988; Caton et al., 1989; Drake and Wallach, 1989; Miller et al., 1989), and other studies have shown that many patients entering drug abuse treatment facilities suffer from co-occurring psychiatric disorders (Khantzian and Treece, 1985; Rounsaville and Kleber, 1986; Ross et al., 1988; Weiss et al., 1988). The prevalence of psychiatric disorders in patients entering drug abuse treatment is substantially higher than one would expect to find in the general population (Rounsaville and Kleber, 1986; Ross et al., 1988, see Chapter 3). High rates of externalizing disorders have been observed in clinical and epidemiological samples of both adult and adolescent drug abusers (Rounsaville and Kleber, 1985, 1986; Helzer and Pryzbeck, 1988; Ross et al., 1988; Weiss et al., 1988). There is a very large degree of overlap between disruptive behavior disorders and drug use in older adolescents, particularly among those with co-occurring conduct disorder (Windle, 1990; Neighbors et al., 1992; Henry et al., 1993; Riggs et al., 1995). Contextual Factors Factors external to the individual and arising in the social (family setting or peer group) or broader environment may also affect the level of drug use and abuse (IOM, 1994b). The complex interrelationships among these contextual factors underscore the complexity of the pathways of drug use and abuse. Familial Factors A number of family factors may be associated with the development of drug use and abuse. As reviewed in Glantz and Pickens (1992), these may include poor quality of the child-parent relationship, family disruptions (e.g., divorce, acute or chronic stress), poor parenting, parent and/

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Pathways of Addiction: Opportunities in Drug Abuse Research or sibling drug use, parental attitudes sympathetic to drug use, and social deprivation. Parents may confer increased risk of drug abuse on their offspring not only through their genes but also by providing negative role models, and especially by using and abusing drugs as a coping mechanism. Through social learning, children and adolescents internalize the values and expectations of their parents and possibly acquire their maladaptive coping techniques. This has been found to be the case with adolescent cigarette smoking (Isralowitz, 1991) and initiation of marijuana use among adolescents (Bailey and Hubbard, 1990). Further, parental attitudes toward use and abuse also play a role (Barnes and Welte, 1986; Brook et al., 1986b). Among Mexican American adolescents, family influence may have a stronger and more direct positive (or protective) effect than is found among white American youth. This may be particularly true for females and seems to be related to the strength of the family's identification with traditional Hispanic culture (Swaim et al., 1993). African American drug abuse and polydrug abuse may be viewed, in part, as contingency reinforcements for the deprivation of stable family and interpersonal relationships (Brunswick et al., 1992). Among young Native Americans, many of whom are physically isolated on reservations, the primary risk factors for alcohol and illicit drug use are socialization links, family problems, and family dysfunction (Swaim et al., 1989). Finally, although many family-related factors have been identified as possible risk factors for drug abuse, many of these studies have failed to demonstrate the specificity of parental and familial effects because they do not include comparison groups of parents with other chronic disorders. Peer Factors The peer environment also makes a substantial contribution to variation in drug use and abuse (Barnes and Welte, 1986; Oetting and Beauvais, 1987a,b, 1990; Oetting and Lynch, in press). Among older adolescents, peers have a greater effect than parents on drug use and abuse among several groups, including whites, African Americans, Asians, and Hispanics (Newcomb and Bentler, 1986). Typically, adolescent drug use takes place within the context of peer clusters that consist of best friends or very close friends (Oetting and Beauvais, 1987a,b). Drug use among friends, deviance, and time spent with drug-using peers are also associated with moderate alcohol and marijuana use (Kandel et al., 1978; Brook et al., 1992). Peer influence on drug use and abuse may occur in a mutually reinforcing pattern based on the tendency for drug-using adolescents to select similar peers (Kandel, 1985). Studies have not yet demonstrated,

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Pathways of Addiction: Opportunities in Drug Abuse Research however, the influence of peers in the transition from drug use to abuse (Kaplan et al., 1986). Further, the contributing effects of peer influences are likely to be different at different stages of development (Glantz and Pickens, 1992). Sociocultural or Environmental Factors The sociocultural factors that have an impact on drug use or abuse include community drug use patterns (Robins, 1984) and neighborhood disorganization (Sampson, 1985). Growing up and living in a community with high rates of crime, ready availability of drugs, association with delinquent peers, and acceptance of drug use and abuse are all associated with drug abuse (Clayton and Voss, 1981; Elliott et al., 1985; Brook et al., 1988; Cohen et al., 1990; Robins and McEvoy, 1990). The larger sociocultural environment also has important effects on drug use. The frequency and nature of representation of alcohol, tobacco, and illicit drugs in the media (including advertising and modeling by those in the sports and entertainment industries) may have important effects on the normative climate. In addition, social and legal policies (taxes, restrictions on conditions of purchase and use, legal status, enforcement) may have important effects on use and abuse. Ethnographic studies have explored various risk factors for drug use and abuse, as well as the impact of drug abuse on the community. The degree of acculturation and assimilation of individuals and their families into the community has been found to be of some importance as a contextual factor. Among Mexican Americans, it has been noted that several risk factors such as low socioeconomic status, higher school dropout rates, and residing in barrios in large cities exacerbate drug use (Padilla et al., 1979; Carter and Wilson, 1991). In many African American communities, individuals may occupy marginal social positions that prevent access to broader opportunities. This could result in failure to be responsive to dominant social norms. Detachment from conventional norms is expressed in unconventional lifestage roles (Brunswick et al., 1992). In samples of whites, there is typically a termination of drug use in the midtwenties age range, when adult roles of marriage and employment are adopted (Miller et al., 1983; Bachman et al., 1984; Yamaguchi and Kandel, 1985; Kandel et al., 1986). It is not surprising that in some African American populations, drug abuse continues into adulthood since conventional adult roles are not assumed (Brunswick et al., 1992). Yamaguchi and Kandel (1985) found that the African American women in their New York State sample were more likely than white women to continue marijuana use. It has been confirmed (Bennett et al., 1989) that low-income African American women

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Pathways of Addiction: Opportunities in Drug Abuse Research have lower marriage rates than comparable white women. Similarly, young African American men have nearly double the unemployment rate of white men (U.S. Bureau of the Census, 1988). Native American youth interact on reservations, which are physically isolated from other communities. In these communities, unemployment rates are high and result in conditions in which drug use can flourish (Oetting et al., 1989). Furthermore, among Native American adolescents, school adjustment is a serious problem and dropout rates are high (Chavers, 1991). Additionally, delinquency and crime are strongly linked to drug use, and there is increasing involvement of reservation youth in gangs. Alternatively, the environment can reinforce a protective sense of self-worth, identity, safety, and environmental mastery. Neighborhood and community factors may also serve to protect individuals from drug use and abuse. For example, restrictions on tobacco use in public places are statements of the preferences of the larger community. Such restrictions also reduce the number of opportunities to use tobacco. Restrictions on smoking in public places reinforce the norm that tobacco use is not acceptable (IOM, 1994a). RESEARCH OPPORTUNITIES Drug abuse is the end product of a series of biological, psychosocial, and contextual (social and environmental) factors that have complex interrelationships. Although, there has been substantial progress in identifying the many correlates of drug use, there is a dearth of research on the correlates of abuse and dependence and on the protective factors that are associated with decreased likelihood of abuse and dependence. Additionally, much of the research in the etiology of drug abuse has been conducted within specific disciplines, with little integration across multiple fields. For example, studies of social factors linked to drug abuse often fail to include key biological factors, and studies of the genetics of drug abuse rarely include assessments of the social context in which drug abuse occurs. Therefore, to advance progress in this area of research there is a need for multidisciplinary studies on the variables associated with the development of drug abuse. Protective Factors Although risk reduction is the goal of many prevention programs, another approach is to enhance protective factors. At the present time, however, there has been little longitudinal research on protective factors

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Pathways of Addiction: Opportunities in Drug Abuse Research and little, if any, research on the transition from use to abuse and dependence. Several investigators have noted that protective factors can moderate the effects of risk conditions, thereby reducing vulnerability and enhancing resiliency (Garmezy, 1985; Werner, 1989; Brook et al., 1990; Rutter et al., 1990). Protective factors that have been suggested based on analyses of cross-sectional data include a positive mutual attachment between parent and child (Brook et al., 1990), nondeviant siblings, academic achievement, positive group norms (Hawkins et al., 1992), and dimensions of conventionality such as low rebelliousness and adherence to broad social norms. Moreover, the effect of one parent's drug use can be offset by the nonuse of the other parent. Additional protective factors that have been identified in young adulthood include employment, marriage, and childrearing responsibilities. It has been noted that several protective factors can ameliorate the negative effects of exposure to extreme stress (Garmezy, 1985). These include the child's temperament, a supportive family, and an external support system that reinforces the child's efforts at coping (Brook et al., 1986a; Labouvie and McGee, 1986). Further research is needed, however, to determine which protective factors are relevant at different developmental stages, and more attention also needs to be given to mechanisms by which protective factors influence the onset and progression of drug abuse. Additionally, research on drug use has documented substantial racial and ethnic differences in drug use among adolescents, such as lower use of tobacco products among African American adolescents than white adolescents (IOM, 1994a; Johnston et al., 1995). The reason for this particular difference is unclear; influences may include the church, cultural consensus against youth tobacco use, or lack of attention from advertisers (IOM, 1994a). Research should be conducted to enhance understanding of racial and ethnic differences in the acceptability of tobacco use and how these differences may be used in the design of prevention interventions related to other drugs of abuse. Risk Factors Numerous longitudinal studies have identified the childhood antecedents of adolescent drug use (e.g., Kellam et al., 1983; Pulkkinen, 1983; Baumrind and Moselle, 1985; Block et al., 1986; Brook et al., 1986a). However, far less research has been done on identifying childhood risk factors associated with drug abuse and dependence that are not associated with behavior problems but with individual vulnerability factors (such as genetic predisposition and emotional disorders). Additionally, there has

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Pathways of Addiction: Opportunities in Drug Abuse Research been little research on exposure to environmental factors that promote exposure to addictive drugs. Furthermore, there has been little hypothesis-based research to distinguish between causal factors and vulnerability factors for the development of drug abuse and dependence. Prospective longitudinal studies, especially of samples at high risk for drug abuse, would be useful in identifying risk factors and in discriminating between risk factors specifically associated with drug abuse and those that emanate from the broader context of deviant behavior. Additional work is also needed on the role of risk factors and protective factors at discrete developmental stages, particularly the transition from adolescence to adulthood, which has received scant attention. It is important to obtain a deeper understanding of the complex ways in which family factors affect adolescent drug use, including the role both of parents and of siblings. There is a striking lack of controlled family studies designed to address the role of familial factors that are critical for identifying patterns of expression of drug abuse and co-occurring psychiatric disorders; for testing the classic modes of genetic transmission of drug abuse; for determining the role of sex-specific patterns of transmission of drug abuse; and for elucidating the role of genetic and environmental factors and their interaction. The interaction of individual and familial risk factors in producing vulnerability to drug abuse also requires further study. For example, recent evidence suggests that parent and child psychopathology may occur in a mutually interactive fashion, with maternal depression elicited by offspring with behavior problems (Blanz et al., 1991). Unique environmental factors may also play significant roles in determining which children within a family are at risk. In other words, one cannot assume that all children within a single family will experience the same environment, including their interactions with significant others. Both transmitted and nontransmitted family factors, as well as unique environmental factors, have been shown to have a major impact on the development of drug abuse (Pickens et al., 1991). Environmental risk factors tend to operate most strongly in children with genetic vulnerability (Rutter et al., 1990). It is therefore critical to identify the joint role of environmental and genetic factors in the etiology of drug abuse. The genetic epidemiological approach, which focuses on the joint effects of the contributions of host, agent, and environment, provides a powerful paradigm by which to gain an understanding of the interaction of variables for drug abuse. Several cohorts of subjects should be studied, including half-siblings, which would permit identification of nongenetic familial factors that may potentiate underlying vulnerability; fraternal twins, which would provide clues to the environmental risk and protec-

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Pathways of Addiction: Opportunities in Drug Abuse Research tive factors for drug abuse; and migrants, which would provide an opportunity to elucidate the role of cultural factors while controlling for genetic and familial factors. Finally, the continued investigation of cohorts of twins and adoptees, particularly in studies that are designed specifically to reveal the mechanisms through which genes exert their influence on drug abuse vulnerability, are also likely to be fruitful. A family history of drug abuse is one of the most important risk factors for the development of drug abuse. However, the extent to which the increased risk is attributable to genetic factors involved in the metabolic, physiological, or subjective effects of drugs or to shared environmental factors such as impaired family relationships, negative role modeling, or, indirectly, transmission of psychopathology, should be examined. There is a need for more studies that can discriminate the roles of genetics and social environment, and their interaction in the development of drug abuse. Genetic epidemiological paradigms such as adoption studies, twin studies, migrant studies, multigenerational family studies, and high-risk studies are particularly important methods for identifying the specific sources of familial influences on drug abuse. Research and treatment programs for drug abuse and psychiatric disorders have generally proceeded independently, with little emphasis on the large overlap between them. Indeed, treatment programs for drug abuse often require cessation of psychotropic medication as an admission requirement. Evidence from retrospective studies of drug abusers, and from a growing number of prospective studies, reveals a link between signs of emotional and behavioral problems beginning in early childhood and the subsequent development of drug abuse. Studies are needed to elucidate the specific mechanisms for the development of drug abuse secondary to psychiatric disorders such as bipolar illness, depression, anxiety disorders, and learning disabilities. The committee recommends multidisciplinary research to investigate the combined effects of biological, psychosocial, and contextual factors as they relate to the development of drug use, abuse, and dependence. The committee further recommends that studies be of long enough duration to enable follow-up of participants in determining the role of risk and protective factors related to the transition from use to abuse and dependence. Research areas should include the role of the following: family factors in the etiology of drug use and abuse; psychopathology as a precursor to drug use and abuse in adolescents and adults; risk and protective factors related to drug use and abuse, especially during discrete developmental stages; and childhood risk and protective factors that are associated with adult drug abuse and dependence.

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