Origins and Pathways to Drug Abuse

Research Findings from February, 2005 Director's Report

This section lists selected summaries from NIDA funded research projects that investigate the origins and pathways to drug abuse. The summaries provided were selected from recent issues of the Director's Report to the National Advisory Council on Drug Abuse. For a more comprehensive listing of NIDA funded projects see the Director's Report.

Acetaldehyde Enhances Acquisition of Nicotine Self-Administration in Adolescent Rats

Tobacco use has one of the highest rates of addiction and relapse of any abused drug. Paradoxically, however, in animal models of reinforcement nicotine appears weak compared to other abused drugs. The reinforcing effects of tobacco smoke may be greater than nicotine alone due to complex interactions between the many constituents of tobacco smoke. One such constituent, acetaldehyde, has been thought to be reinforcing when inhaled. This compound may, therefore, augment nicotine's reinforcing properties. Juvenile and adult male rats were implanted with intravenous catheters and tested for nicotine self-administration 4 days later, at postnatal day 27 or 90, respectively. Animals were offered one of the following solutions: nicotine (30 mg/kg/injection), acetaldehyde (16 mg/kg/inj), nicotine (30 mg/kg/inj) plus acetaldehyde (16 mg/kg/inj), or saline. The youngest animals responded significantly more for nicotine plus acetaldehyde than for saline or for either drug alone. Tests with receptor antagonists indicated that these drug effects are mediated by central, but not peripheral, nicotinic receptors. There was an age-related decline in self-administration of nicotine plus acetaldehyde. Taken together, these results indicate that acetaldehyde, at the low concentrations found in tobacco smoke, interacts with nicotine to increase responding in a stringent self-administration acquisition test where nicotine alone is only weakly reinforcing, and that adolescent animals are more sensitive to these actions than adults. The authors suggest that animal models of tobacco addiction could be improved by combining acetaldehyde, and possibly other smoke components, with nicotine to more accurately reflect the pharmacological profile of tobacco smoke. Belluzzi, J.D., Wang, R. and Leslie, F.M. Acetaldehyde Enhances Acquisition of Nicotine Self-Administration in Adolescent Rats. Psychopharmacology (epub), 2004.

Rats Reared in Enriched Environments Have More Robust Glutamatergic Neurotransmission in the Prefrontal Cortex and Improved Performance in a Spatial Memory Task Than Animals Reared in Impoverished or Normal Environments

Rearing rats in impoverished (IC) and enriched (EC) environmental conditions alters synaptic plasticity and cognitive processes. Metabotropic glutamate receptors (mGluRs) are known to play a key role in synaptic and behavioral plasticity. In the present study, the effect of rearing conditions on the expression of mGluR proteins in the prefrontal cortex (PFC) was assessed by immunoblotting. A significant difference in the content of prefrontal mGluR1 and mGluR5 (ie group I) and mGluR2/3 (ie group II) was observed between IC and EC rats. To functionally characterize this difference, in vivo microdialysis was used to verify differences in mGluR regulation of extracellular glutamate in the PFC. The results indicate that the capacity of group I and II mGluRs to elevate extracellular glutamate levels was significantly blunted in the PFC of IC rats compared to either EC subjects, or rats reared in normal environmental conditions (ie NIH standards). Group II mGluR receptors regulate performance in a forced T-maze spatial memory task that involves the PFC, and IC rats demonstrated deficits in this task relative to EC rats. These data suggest that reduced mGluR transmission in the PFC produced by impoverished, relative to enriched, rearing environments may contribute to cognitive deficits. Melendez, R.I., Gregory, M.L., Bardo, M.T. and Kalivas, P.W. Impoverished Rearing Environment Alters Metabotropic Glutamate Receptor Expression and Function in the Prefrontal Cortex. Neuropsychopharmacology, 29(11), pp. 1980-1987, 2004.

Differences in Maternal Styles of Rearing May Predispose to or Protect Individuals From the Development of Addiction

While many people experiment with drugs, relatively few individuals develop a true addiction. Dr. Michael Meaney and his colleagues hypothesized that, in rats, such individual differences in the actions of addictive drugs might be determined by postnatal rearing conditions. To test this idea, they investigated whether stimulant- and stress-induced activation of nucleus accumbens dopamine transmission and dopamine-dependent behaviors might differ among adults rats that had been either repeatedly subjected to prolonged maternal separation or a brief handling procedure or left undisturbed (non-handled) during the first 14 days of life. They found that, in comparison with their handled counterparts, maternally separated and non-handled animals are hyperactive when placed in a novel setting, display a dose-dependent higher sensitivity to cocaine-induced locomotor activity and respond to a mild stressor (tail-pinch) with significantly greater increases in nucleus accumbens dopamine levels. In addition, maternally separated animals were found to sensitize to the locomotor stimulant action of amphetamine when repeatedly stressed under conditions that failed to sensitize handled and non-handled animals. Finally, quantitative receptor autoradiography revealed a lower density of nucleus accumbens-core and striatal dopamine transporter sites in maternally separated animals. They also found greatly reduced D3 dopamine receptor binding and mRNA levels in the nucleus accumbens-shell of handled animals. Together, these findings provide compelling evidence that disruptions in early postnatal rearing conditions can lead to profound and lasting changes in the responsiveness of mesocorticolimbic dopamine neurons to stress and psychostimulants, and suggest a neurobiological basis for individual differences in vulnerability to compulsive drug taking. Brake, W.G., Zhang, T.Y., Diorio, J., Meaney, M.J. and Gratton, A. Influence of Early Postnatal Rearing Conditions on Mesocorticolimbic Dopamine and Behavioural Responses to Psychostimulants and Stressors in Adult Rats. European Journal of Neuroscience, 19, pp. 1863-1874, 2004.

Adolescent Rats Do Not Form Learned Associations Between Nicotine and Associated Environmental Cues

Eighteen percent of U.S. teens are smokers and recent preclinical, as well as epidemiological evidence, suggests that adolescents have a differential response to the drug nicotine than is seen in adulthood. Adolescent rats have been shown to be more sensitive to the locomotor activating effects of nicotine, but some studies reveal that they do not develop behavioral sensitization with repeated nicotine treatment. Neuroadaptations involved in the development of sensitization are believed to play a role in the escalation of drug intake that characterizes addiction. Drs. Charles Landry, Ann Kelley, and colleagues have also examined age-related differences in acute locomotor response to nicotine and the development of behavioral sensitization. Furthermore, they determined if there are differences between adolescent and adult rats in drug-paired cue conditioning. In these studies, conducted with male rats, adults were 70 days of age, and adolescents were 28-42 days old. To assess effects of acute nicotine, all rats were injected with 0.1 mg/kg s.c. and observed in photocell activity chambers after habituation. Adolescents were more active than adults in the test chamber upon their initial, non-drug exposure (habituation), and also when they were injected with saline or nicotine. Also, adolescent animals had a greater mean locomotor count after nicotine, compared to their saline-injected controls, for the first 20 min of the test session. Adult animals, however, showed a typical pattern of initial, behavioral suppression, followed by a rise in activity counts over the session. When given 10 days of 0.4mg/kg s.c. nicotine (Adoles/nic, Adult/nic) or saline (Adoles/sal, Adult/sal) paired with 90-min in a discrete environment, Adult/nic rats showed a significant linear trend for increased locomotor activity, but Adoles/nic rats did not. In tests for cue conditioning, rats from all four groups were given a mock injection and locomotor activity was again monitored in the test chamber for 90 min. Adult animals showed the usual conditioned locomotor activation, as ambulation was greater in the Adult/nic group than in Adult/sal animals. However, there was no difference in ambulatory counts between Adolescents from the nic versus the sal groups. The main finding from this study is that adolescents, (i.e., males), do not seem to develop the usual learned associations that are formed between effects of the drug nicotine, and surrounding environmental cues. In adults, incentive motivational properties of these cues are believed to serve as strong ïtriggers' for activating and sustaining smoking behavior. The authors speculate that this difference might be linked to prolonged development of the prefrontal cortex, which continues through the adolescent period, and serves as an important substrate for central mechanisms of attention. Furthermore, in agreement with some earlier studies, the observation that adolescent rats fail to develop nicotine sensitization suggests that plasticity-related changes produced by repeated nicotine may be different from those previously measured in adults. Schochet, T.L., Kelley, A.E. and Landry, C.F. Differential Behavioral Effects of Nicotine Exposure in Adolescent and Adult Rats. Psychopharmacology, 175, pp. 265-273, 2004.

A Non-human Primate Model of the Behavioral and Physiological Effects of Childhood "Stress Inoculation"

Retrospective studies of resilience in humans have indicated that childhood exposure to moderate stress serves to "inoculate" against subsequent stressful experiences and to enhance coping skills that safeguard against the development of stress-related disorders in adolescence and adulthood. Dr. David Lyons and his colleagues have tested this hypothesis in a prospective study on squirrel monkeys. Twenty monkeys were randomly assigned to either intermittent stress inoculation (IS) or a nonstress control condition (NS) for 10 weeks, starting at postnatal week 17 when they had just been weaned but were still emotionally attached to their mothers. For the IS, individual monkeys were removed from their natal group for one hour once a week and placed in a cage adjacent to an unfamiliar adult. This separation induced isolation calls, locomotor agitation, and an increase in cortisol that returned to baseline soon after reunion with the family. At postnatal week 35, each mother-offspring dyad underwent testing in a moderately stressful novel environment to assess offspring anxiety and stress hormone concentrations. At postnatal week 50, after acclimation to an initially stressful wire-mesh box attached to the home cage, the young monkeys were tested for voluntary exploration and play in the box as an inferential measure of anxiety. In the novel environment test, IS compared with NS offspring demonstrated diminished anxiety as measured by decreased maternal clinging, enhanced exploratory behavior, and increased food consumption. IS offspring also had lower basal plasma ACTH and cortisol and lower post-stress corticoptropin and cortisol levels. In the home-cage wire-box test, IS offspring showed enhanced exploratory and play behaviors compared with NS offspring. This study is the first prospective evidence in non-human primates that moderately stressful early experiences strengthen socioemotional and neuroendocrine resistance to subsequent stressors. Dr. Lyons is pursuing studies with this model to investigate resistance to the effects of drugs of abuse, in contrast to models of chronic stress. Additionally, this preclinical model of stress inoculation will be used to elucidate the etiology and neurobiology of stress resistance. Parker, K.J., Buckmaster, C.L., Schatzberg, A.F. and Lyons, D.M. Prospective Investigation of Stress Inoculation in Young Monkeys. Archives of General Psychiatry, 61, pp. 933-941, 2004.

Adolescent Predictors of Young Adult and Adult Alcohol Involvement and Dysphoria in a Prospective Community Sample of Women

The adolescent predictors of later alcohol involvement (AI), dysphoria (D), and their shared association (AD) among women have not been adequately established. Three waves of data from an ethnically diverse community sample of women, assessed over 16 years are used to study how various psychosocial factors in adolescence influenced later drinking, depression, and their shared association. Structural equation models revealed that several adolescent ecodevelopmental and social development model variables influenced their later outcome in young adulthood and adulthood. The strongest relation was between adolescent Social Conformity and adult AD (b = -.46) over a 16-year period, emphasizing the impact of this construct. Numerous other relations were revealed. For instance, less satisfaction with school during adolescence predicted adult AI. Having a good bond to the family in adolescence predicted a lower quantity of alcohol consumed during adulthood. Lower satisfaction with "what you want to be" during adolescence predicted young adult D. Higher levels of adolescent relationship satisfaction and school satisfaction predicted less suicidal ideation as an adult. Prevention interventions focusing on increasing socially conforming attitudes and on strengthening relationships both in and out of the home during adolescence are likely to be effective in reducing aspects of AI, D, and AD for women in the general community. Locke, T. F., and Newcomb, M.D. Adolescent Predictors of Young Adult and Adult Alcohol Involvement and Dysphoria in a Prospective Community Sample of Women. Prevention Science, 5, pp. 151-168, 2004.

Adolescent Onset Bipolar Disorder Associated with Risk for Substance Use Disorder

This study further investigated the previously reported elevated risk for substance use disorders (SUD) among children and adolescents with bipolar disorder (BPD), addressing some of the previous methodological weaknesses. The authors compared 57 subjects with early onset BPD with controls of similar age and socioeconomic status. Bipolar disorder was found to constitute a significant risk factor for substance use disorder in adolescence; this relationship held even when conduct disorder (commonly associated with both BPD and SUD) was taken into account. Moreover, as previously reported, adolescent-onset BPD rather than childhood-onset was the greater predictor. Although early onset bipolar disorder is relatively rare among the mental disorders, it is severe; thus, this study points to a potent risk factor that may help identify a high-risk group that could benefit from early intervention for bipolar disorder with possible implications for preventing SUD. Wilens, T.E., Biederman, J., Kwon, A., Ditterline, J., Forkner., P., Moore, H., Swezey, A., Snyder, L., Henin, A., Wozniak, H., and Faraone, S.V. Risk for Substance Use Disorders in Adolescents with Bipolar Disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 43, pp. 1380-1386, 2004.

Age at First Use and Psychopathology as Risk Factors for Substance Use Disorder

This paper explores the issue of early drug use as a risk factor for adolescent substance use disorder (SUD), and the possible role of comorbid conduct problems in explaining this association. Sophisticated statistical tests were applied to longitudinal data from a large population-based sample, the Great Smoky Mountains Study, assessed annually between ages 9 and 16. Of note, drug use before age 13 was a strong predictor of transition to SUD, and early use remained a risk factor even in the absence of conduct disorder. Boys with a history of depression were at increased risk for SUD, and girls with anxiety experienced an increased risk at age 16. Findings from such large population-based studies can help target populations at higher risk for drug abuse for appropriate preventive interventions. Sung, M., Erkanli, A., Angold, A., and Costello, E.J. Effects of Age at First Substance Use and Psychiatric Comorbidity on the Development of Substance Use Disorders. Drug and Alcohol Dependence, 75, pp. 287-299, 2004.

Neurobehavior Disinhibition in Childhood Predicts Suicide Potential and Substance Use Disorder by Young Adulthood

The objectives of this study were to (1) determine whether two factors that are established components of the risk for substance use disorder (SUD) also impact on the risk for suicide; and (2) evaluate whether SUD manifest by early adulthood predicts suicide propensity. Neurobehavior disinhibition assessed in 227 boys at ages 10-12 and 16 and parental history of SUD were prospectively evaluated to determine their association with the risk for SUD and suicide propensity between ages 16 and 19. The results indicated that neurobehavior disinhibition at age 16 predicts suicide propensity between ages 16 and 19 (p = .04). A trend was observed (p = .08) for SUD manifest between ages 16 and 19 to predict suicide propensity during the same period. Maternal SUD is directly associated with son's SUD risk but not suicide propensity. Paternal SUD predicts son's neurobehavior disinhibition that, in turn, predisposes to SUD. A direct relation between paternal SUD and son's suicide propensity was not observed. These findings suggest that neurobehavior disinhibition, a component of the liability of SUD, is also associated with suicide risk. These results are discussed within a neurobehavioral framework in which prefrontal cortex dysfunction is hypothesized to underlie the risk for these two outcomes. Tarter, R.E., Kirisci, L., Reynolds, M., and Mezzich, A. Drug and Alcohol Dependence 76, S45-S52, 2004.

Early Childhood Misbehavior Associated with Risk of Becoming Tobacco Dependent

In this study, the authors focused on signs of early childhood misbehavior that might be linked to the risk of becoming tobacco-dependent. Standardized teacher ratings of misbehavior were obtained for an epidemiologic sample of first graders entering an urban mid-Atlantic public school system in 1985 and 1986. Fifteen years later, 1,692 of the students were reassessed. As adults, 962 participants indicated that they had tried tobacco at least once; 66% of the 962 had become daily users. Latent class analysis of items on the Fagerstrom Test for Nicotine Dependence gave evidence of three classes pertinent to tobacco dependence syndrome in smokers by young adulthood: one nondependent class of smokers (50% of smokers), a class of smokers experiencing a moderate number of dependence features (31%), and a third class that was more severely affected (19%), as manifest in the need to smoke immediately after waking and smoking when ill. With or without adjustment for covariates, higher levels of teacher-rated childhood misbehavior at entry into primary school were associated with a modest excess risk of becoming tobacco-dependent by young adulthood (risk ratio = 1.6, 95% confidence interval: 1.1, 2.5). Interventions that seek to improve childhood behavior might reduce early onset tobacco smoking and risk of tobacco dependence among smokers. Storr, C.L., Reboussin, B.A., and Anthony, J.C. Am J Epidemiol, 15, 160, pp. 126-130, 2004.

Low Parent Involvement Related to Youth Substance Abuse

This study developed a scale-based method for identifying adolescents with low-parent involvement and examined effects on the development and course of alcohol use disorders (AUDs). The participants were 361 adolescents (ages 14 to 17 years) from two-parent families recruited from clinical and community sources. Cluster analysis of questionnaire items describing mother and father involvement identified 75 adolescents with low-parent involvement (i.e., Neglect). Compared with reference adolescents, Neglect adolescents were significantly more likely to be influenced by social pressure to drink alcohol. Among community participants, Neglect adolescents were more likely to develop AUDs. Among adolescents receiving treatment for AUDs, those in the Neglect group showed more improvement during a 1-year follow-up period. The results indicate that inadequate parent involvement may be a form of neglect. Clark, D.B., Thatcher, D.L., and Maisto, S.A. Adolescent Neglect and Alcohol Use Disorders in Two-Parent Families. Child Maltreatment 9, pp. 357-370, 2004.

The Natural History of Alcohol Use Disorders

This study examined clinically relevant research on the development, course and outcomes of adolescence alcohol use disorders (AUDs), using observational studies with adolescent samples selected for inclusion based on systematic assessment of AUDs and clinical relevance. Articles on childhood predictors, characteristics, course, complications and adult outcomes of adolescent AUDs were reviewed. Results indicate that the developmental trajectory toward adolescent AUDs begins with the emergence of childhood mental disorders. These problems are transmitted from parent to child in a developmentally specific fashion, reflect psychological dysregulation dimensions and predict adolescent AUDs. While most DSM-IV AUD diagnostic criterion items are valid for adolescents, tolerance and impaired control items are problematic, and some adolescents with significant alcohol problems are not identified by this diagnostic system. Understanding the psychosocial and biomedical complications that accompany AUDs requires attention to factors other than alcohol involvement itself, including childhood maltreatment and comorbid psychopathology. While some adolescents with AUDs manifest chronic alcohol dependence in adulthood, a substantial proportion overcome alcohol problems and transition to abstinence or normative drinking. While alcohol consumption may be the primary treatment focus, other important consequences, comorbidities and complications need to be addressed for successful developmental outcomes to result. Clark, D.B. The Natural History of Alcohol Use Disorders, Addiction, 99, pp. 5-22, 2004.

Antecedents and Outcomes of Marijuana Use Initiation during Adolescence

This study identified similarities and differences in risk factors for marijuana use initiation from grades 7 to 8, grades 8 to 9, and grades 9 to 10, and examined differences between earlier initiates, later initiates, and nonusers on various problem behaviors at grade 10. Longitudinal data were used to examine predictors and outcomes associated with marijuana initiation from grade 7 (N = 1,955) to grade 10 (N = 909). Participants completed yearly surveys to assess problem behaviors, social influences, and marijuana-related attitudes and behavior. Results showed that earlier initiates were more likely than later initiates to exhibit problem-related marijuana use, hard drug use, polydrug use, poor grades, and low academic intentions at grade 10. Across ages, initiation was predicted by smoking, frequency of marijuana offers, and poor grades. Results provided some evidence for a shift from familial to peer influence on marijuana initiation with increasing age. Marijuana-related beliefs were relatively weak predictors of initiation at all ages after controlling for pro-marijuana social influences and engagement in other types of substance use and delinquent behavior. Results emphasize the importance of early intervention and identify a wide range of potentially modifiable risk factors that may be targeted. Ellickson, P.L., Tucker, J.S., Klein, D.J., and Saner, H. Prev Med., 39, pp. 976-984, 2004.

Attitudes toward Alcohol and Drug-free Experience among College Students

This study examined prospective relations between attitudes toward alcohol use and drug-free experience and alcohol consumption and problems in 231 undergraduate students (73% women). Attitude toward drug-free experience was hypothesized to moderate the alcohol attitude--behavior relationship. Participants were assessed twice, separated by a 30-day interval. Attitude toward alcohol use at Time 1 was associated with alcohol consumption at Time 2. Time 1 attitude toward alcohol use and the interaction between the attitude variables were associated with problems at Time 2, indicating that attitude toward alcohol use was less associated with alcohol problems among participants with more positive attitudes toward drug-free experience. Attitude toward drug-free experience acted as a protective factor, reducing the relationship between alcohol attitude and alcohol-related problems. Simons, J.S., and Gaher, R.M. Attitudes toward Alcohol and Drug-free Experience among College Students: Relationships with Alcohol Consumption and Problems. Am J Drug Alcohol Abuse, 30, pp. 461-471, 2004.

Religious Activity and Risk Behavior Among African American Adolescents

This study examines how religious activity is associated with risk behaviors, concurrently and developmentally among urban African American adolescents. Seven hundred and five African American youths were interviewed annually during high school. Retention rates for the study exceeded 90%. Frequency of religious activity, sexual intercourse, and alcohol, cigarette, and marijuana use were assessed at each wave. Growth curve analyses found negative concurrent associations between religious activity and each of the four risk behaviors. The developmental effects of religious activity varied by gender. Higher levels of religious activity in 9th grade predicted smaller increases in marijuana use among males and cigarette use among females. In addition, larger decreases in religious activity during high school were associated with greater increases in alcohol use among males and sexual intercourse among females. During high school, religious activity limits the development of certain types of risk behavior among African American youth, even after controlling for reciprocal effects. Steinman, K.J., and Zimmerman M.A. Religious Activity and Risk Behavior among African American Adolescents: Concurrent and Developmental Effects. Am J Community Psychol., 33, pp. 151-161, 2004.

Life Transitions Predict Depression and Alcohol Use

This study examined longitudinally the relationship between depressive symptoms and alcohol use in a sample of black youth. Participants were 458 black males and females interviewed annually during the high school years and then for 3 years during the transition to adulthood. The relationship was examined using growth curves with Hierarchical Linear Modeling. The results suggest that depressive symptoms decrease over time, whereas the use of alcohol increases. The findings also suggest that youths use alcohol as a way to cope with depressive symptoms and that males are more likely to use alcohol as self-medication. The results also indicate that changes in alcohol use do not predict depressive symptoms, but that life changes associated with the transition to adulthood, such as attending college, predict changes in depressive symptoms and alcohol use. Findings highlight the role of depressive symptoms for predicting alcohol use among black youth and the role of significant life transitions in altering the pattern of alcohol use presented previously by these youths. Repetto, P.B., Zimmerman, M.A., and Caldwell, C.H. A Longitudinal Study of the Relationship between Depressive Symptoms and Alcohol Use in a Sample of Inner-city Black Youth. J Stud Alcohol., 65, pp. 169-178, 2004.

Racial/Ethnic Differences in Cigarette Smoking Initiation and Progression to Daily Smoking

Using data from the National Longitudinal Study of Adolescent Health, this study was designed to identify individual and contextual factors that influence cigarette smoking initiation and progression to daily smoking among non-Hispanic Black, Hispanic, and non-Hispanic White adolescents. Findings confirmed differences in patterns of smoking onset and progression to daily smoking among racial/ethnic groups. Hispanic youth had the highest rates of smoking onset, and White youth had the highest rates of progression to daily smoking. Black youth consistently had the lowest rates for both smoking outcomes. There were more common predictors than ethnic-specific predictors of adolescent smoking and individual factors were much more important predictors than contextual factors. The authors concluded that universal prevention and intervention efforts would reach most adolescents, regardless of race/ethnicity. Kandel, D.B., Kiros, G.E, Schaffran, C., and Hu, M.C. Racial/Ethnic Differences in Cigarette Smoking Initiation and Progression to Daily Smoking: A Multilevel Analysis. American Journal of Public Health, 94, pp. 128-135, 2004.

Parent Support, Peer Support and Adolescent Substance Use

Using a multi-ethnic sample of adolescents, this study tested comparative effects of parent and peer support (confiding and emotional) on adolescent substance use with data from two assessment points. Results suggest parent support was inversely related to substance use and peer support was positively related to substance use (suppression effect). Effects were mediated through pathways involving self-control and risk-taking tendency. Wills, T.A., Resko, J.A., Ainette, M.G. and Mendoza, D. Role of Parent Support and Peer Support in Adolescent Substance Use: A Test of Mediated Effects. Psychol Addict Behav., 18, pp. 122-134, 2004.

Behavioral Undercontrol and Parenting

This study examined the associations among parental alcoholism, behavioral undercontrol, and parenting in the development of drug use disorders in emerging adulthood. Findings suggest that parental alcoholism is associated with less parental discipline and more adolescent behavioral undercontrol, which in turn raises the risk of later drug disorders. Parent support has a protective buffering effect on the link between undercontrol and drug use disorders, except in cases of high levels of behavioral undercontrol. King, K.M., and Chassin, L. Mediating and Moderating Effects of Adolescent Behavioral Undercontrol and Parenting in the Prediction of Drug Use Disorders in Emerging Adulthood. Psychology of Addictive Behaviors, 18, pp. 239-249, 2004.

The Long-Term Negative Impact of High-Risk Peer Group Affiliations

Adolescents' self-identified peer group affiliation is associated with health risk behaviors such as involvement in substance use and violence. This prospective study examined the association between peer group self-identification during high school and psychosocial functioning five years later among a sample of continuation high school students (i.e., students attending alternative public schools). Participants were recruited as part of Project TND, a substance use prevention project conducted in 21 school districts from a five-county region of Southern California. The sample included 532 students, ranging in age from 19 to 24 years most of whom were male (57%) and half were Latino (50%). Participants named the peer group which they felt "most a part of." Responses were collapsed into four general group categories: high-risk youth, jocks-hotshots, regulars, and others. Results indicated that students who self-identified with high-risk peer groups while in continuation high school were most likely to report involvement in drug use and violence during young adulthood, and they were significantly less likely to have graduated from high school or secure stable employment. Sussman, S., Unger, J.B. and Dent, C.W. Peer Group Self-Identification among Alternative High School Youth: A Predictor of Their Psychosocial Functioning Five Years Later. International Journal of Clinical and Health Psychology, 4, pp. 9-25, 2004.

Adolescent Depression and Suicide Risk Are Associated with Sex and Drug Use Behavior

Although both depression and suicide in adolescents have been associated with drug use and early sexual intercourse, the relationship has not been systematically studied in a nationally representative sample. Sixteen patterns of combined sex and drug use behaviors were obtained through analysis of responses to Wave I of the National Longitudinal Study of Adolescent Health conducted from September 1994 through December 1995. Analyses tested correlations between behavior patterns and current depression, serious suicidal ideation, and previous suicide attempt, controlling for gender, race/ethnicity, family structure, and parent education. Compared to youth who abstain from risk behaviors, involvement in any drinking, smoking, and/or sexual activity was associated with significantly increased chances of depression, suicidal ideation, and suicide attempts. These problems were highest among youth who engaged in illegal drug use. There were few differences between boys and girls who abstain from sex and drug behaviors. Girls were less likely than boys to engage in high-risk behaviors, but those who did tended to be more vulnerable to depression, suicidal ideation, and suicide attempt. Hallfors, D.D., Waller, M.W., Ford, C.A., Halpern, C.T., Brodish, P.H., and Iritani, B. Adolescent Depression and Suicide Risk - Association with Sex and Drug Behavior. Am J of Preventive Med., 27(3), pp. 224-231, 2004.

Effects of Good Inhibitory Control on Negative Emotions and Alcohol Use

Studies on the relation between negative affect and later alcohol use have provided mixed results. To disentangle the diverse elements of negative affect and explain these inconsistent findings some have examined the moderating role of good inhibitory control. This longitudinal investigation examined the independent relationships between three components of negative affect (i.e., depressed mood, fear, and anger) and alcohol use initiation in a sample of aggressive boys, as well as the moderating effect of good inhibitory control. Increased anger and decreased fearfulness were associated with an increased risk for alcohol use initiation only for boys with moderate to low levels of inhibitory control. However, depressed mood predicted alcohol use initiation for boys with good inhibitory control. Pardini, D., Lochman, J. and Wells, K. Negative Emotions and Alcohol Use Initiation in High-Risk Boys: The Moderating Effect of Good Inhibitory Control. Journal of Abnormal Child Psychology, 32(5), pp. 505-518, 2004.

Perceived Life Chances and Alcohol Use

The relationship between low perceived chances for success in life and binge drinking was examined in a sample of economically disadvantaged, predominantly black and Hispanic student, urban adolescents (N = 774) from 13 inner-city schools. Subjects completed confidential questionnaires in the 7th, 8th, and 9th grades. Eight items measured students' estimation of achieving certain adaptive life goals. Students who reported that they typically drink five or more drinks per drinking occasion were identified as binge drinkers. Results indicated that rates of binge drinking increased and perceived life chances decreased for both boys and girls from the 7th to 9th grade. Moreover, higher perceived life chances in the 7th grade predicted less binge drinking in the 8th grade, whereas binge drinking in the 8th grade predicted lower perceived life chances in the 9th grade, controlling for change over time in both variables. Griffin, K.W., Botvin, G.J., Nichols, T.R. and Scheier, L.M. Low Perceived Chances for Success in Life and Binge Drinking among Inner-city Minority Youth. Journal of Adolescent Health, 34, pp. 501-507, 2004.

Self-esteem and Alcohol Use

Prior studies have found inconsistent relationships between measures of self-concept and adolescent alcohol use. This study explored whether the link between various measures of self-concept and alcohol use depends on gender and whether negative rather than positive self-esteem (i.e., self-derogation) might be more useful in predicting alcohol use. Students (N = 1459) attending 22 middle and junior high schools in New York City completed surveys that included measures of efficacy, self-derogation, and alcohol use. Participants completed surveys at baseline, 1-year follow-up, and 2-year follow-up. Findings indicate that lower efficacy was related to greater self-derogation a year later across gender. Increased self-derogation predicted higher alcohol use for girls but not boys. These findings are congruent with a literature highlighting the importance of negative thoughts about the self in drinking behavior for women but not men. Epstein, J.A., Griffin, K.W. and Botvin, G.J. Efficacy, Self-derogation, and Alcohol Use among Inner-city Adolescents: Gender Matters. Journal of Youth & Adolescence, 33, pp. 159-166, 2004.

A Nonverbal Test of Memory for Alcohol Commercials

There is suggestive evidence that televised alcohol commercials may affect the alcohol consumption of adolescents. However, it has been difficult to assess exposure to and memory of such ads because these complex everyday occurrences have numerous nonverbal, visual features that may not be completely assessed by eliciting verbal responses to them. This study investigated a nonverbal test of memory for alcohol commercials. Participants included 750 adolescents from 6 public middle and 3 public high schools who completed a nonverbal test of memory, tailored to detect prominent visual features of remembered alcohol ads. The results showed that independent judges reliably coded primary features of remembered advertisements along most dimensions, and the test met important criteria for validity in comparisons with other measures. Stacy, A.W., Pearce, S.G., Zogg, J.B., Unger, J., and Dent, C.W. A Nonverbal Test of Naturalistic Memory for Alcohol Commercials. Psychology and Marketing, 21, pp. 295-322, 2004.

Post-September 11 Increases in Substance Use Persist in Manhattan

Early analyses following the September 11, 2001 terrorist attacks on New York City showed an increase in cigarette, alcohol, and marijuana use. To determine whether these increases would persist, a random-digit dial phone survey was conducted to estimate the prevalence of increased substance use among residents of New York City six to nine months after the attacks. Among 1,570 adults, 9.9% reported an increase in smoking, 17.5% an increase in alcohol use, and 2.7% an increase in marijuana use compared to the month before September 11. These increases were comparable to increases reported in the first one to two months after September 11. Persons who increased use of cigarettes were more likely than those who did not to report symptoms consistent with posttraumatic stress disorder (PTSD) in the past month (4.3% and 1.2% respectively). Depression was more common among those who increased use of cigarettes (14.6% and 5.2% respectively), alcohol (11.8% vs. 5.2%), and marijuana (34.1% vs. 5.3%). Among residents living in Manhattan below One Hundred Tenth Street, the prevalence of PTSD and depression declined by more than half in the first six months after September 11, while the increase in substance use did not decline substantially. These results suggest that the increase in substance use after a disaster may be a cause for public health concern in the long-term. Vlahov, D., Galea, S., Ahern, J., Resnick, H., Boscarino, J.A., Gold, J., Bucuvalas, M. and Kilpatrick, D. Consumption of Cigarettes, Alcohol, and Marijuana among New York City Residents Six Months After The September 11 Terrorist Attacks. American Journal of Drug and Alcohol Abuse, 30(2), pp. 385-407, 2004.

Manhattan Residents' Substance Abuse Increase Sustained After September 11 Attacks

This study compared reports of increased substance use in Manhattan 1 and 6 months after the September 11, 2001, terrorist attacks. Data from 2 random-digit-dial surveys conducted 1 and 6 months after September 11 showed that 30.8% and 27.3% of respondents, respectively, reported increased use of cigarettes, alcohol, or marijuana. These sustained increases in substance use following the September 11 terrorist attacks suggest potential long-term health consequences as a result of disasters. Vlahov, D., Galea, S., Ahern, J., Resnick, H. and Kilpatrick D. Sustained Increased Consumption Of Cigarettes, Alcohol, And Marijuana Among Manhattan Residents After September 11, 2001. American Journal of Public Health, 94(2), pp. 253-254, 2004.

Attention-Deficit/Hyperactivity Disorder and the Substance Use Disorders: The Nature of the Relationship, Subtypes at Risk, and Treatment Issues

There is a strong literature supporting a relationship between ADHD and SUD. Clearly, ADHD adolescents with conduct or bipolar disorder as part of their clinical picture are at the highest risk for SUD. ADHD without comorbidity appears to confer an intermediate risk factor for SUD that appears to manifest in young adults and college students. Both family genetic and self-medication influences may be operational in the development and continuation of SUD in ADHD subjects: however, systematic data are lacking. Patients with ADHD and SUD require multi-modal interventions incorporating addiction and mental health treatment. Pharmacotherapy in individuals with ADHD and SUD needs to take into consideration abuse liability, potential drug interactions, and compliance concerns. Although the existing literature has provided important information on the relationship of ADHD and SUD, it also points to a number of areas in need of further study. The mechanism by which untreated ADHD leads to SUD and the risk reduction of ADHD treatment on later SUD, needs to be understood better. The influence of adequateness of treatment of ADHD on later SUD needs to be delineated. Given the prevalence and major morbidity and impairment caused by SUD and ADHD. Prevention and treatment strategies for these patients need to be developed and evaluated further. Wilens, T.E. Attention-Deficit/Hyperactivity Disorder and the Substance Use Disorders: The Nature of the Relationship, Subtypes at Risk, and Treatment Issues. Psychiatr. Clin. North Am., 27, pp. 283-301, 2004.

Risk of Substance Use Disorders in Adolescents with Bipolar Disorder

Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD. Probands with DSM-IV BPD (n=57, mean age +/- SD=13.3 +/- 2.4 years) and without DSM-IV BPD (n=46, 13.6 +/- 2.2 years) were studied. Structured psychiatric interviews and multiple measures of SUD were collected. Bipolar disorder was associated with a highly significant risk factor for SUD (32% versus 7%, Z=2.9, p=.004) that was not accounted for by conduct disorder (adjusted odds ratio=5.4, p=.018). Adolescent-onset BPD (> or =13 years) was associated with a higher risk of SUD compared with those with child-onset BPD (chi1=9.3, p=.002). These findings strongly indicate that BPD, especially adolescent onset, is a significant risk factor for SUD independently of conduct disorder. Wilens, T.E., Biederman, J., Kwon, A., Ditterline, J., Forkner, P., Moore, H., Swezey, A., Snyder, L., Henin, A., Wozniak, J. and Faraone, S.V. Risk of Substance Use Disorders in Adolescents with Bipolar Disorder. J Am. Acad. Child Adolesc. Psychiatry, 43, pp. 1380-1386, 2004.

Methylphenidate Has Some Potential for Abuse

Methylphenidate is used to treat Attention Deficit Hyperactivity Disorder in children and adolescents. However, its abuse potential has not been well characterized, although it produces behavioral effects similar to those observed with other abused stimulants, such as d-amphetamine and cocaine. Investigators at the University of Kentucky, Lexington, KY, aimed to characterize the abuse potential of oral methylphenidate relative to oral d-amphetamine. Ten drug-abusing volunteers were recruited to participate in this study, which consisted of seven dose conditions: methylphenidate (16, 32 and 48 mg), d-amphetamine (8, 16 and 24 mg) and placebo. The reinforcing effects of these drugs were assessed during a self-administration session with a modified progressive-ratio procedure. Subject-rated, performance and physiological effects were assessed concurrently during both the sampling and self-administration sessions. The intermediate dose of methylphenidate and d-amphetamine increased responding significantly above placebo levels. Both methylphenidate and d-amphetamine produced dose-dependent increases in stimulant-like subject ratings (e.g. Active, Alert, or Energetic and High). These findings are consistent with epidemiological data and previous findings from laboratory studies that suggest methylphenidate has at least some abuse potential. Stoops, W.W., Glaser, P.E., Fillmore, M.T. and Rush, C.R. Reinforcing, Subject-rated, Performance and Physiological Effects of Methylphenidate and D-amphetamine in Stimulant Abusing Humans. J Psychopharmacology, 18(4), pp. 534-543, 2004.