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National Institute on Drug Abuse

Director's Report to the National Advisory Council on Drug Abuse

February 1997

Research Findings

Epidemiology, Etiology and Prevention Research

Monitoring The Future Results from the 1996 Monitoring the Future Study were released on December 19, 1996 (Lloyd Johnston, et al). Following are the most significant findings:

Between 1995 and 1996 use of cigarettes and marijuana increased notably among 8th and 10th graders. In addition, fewer of these students expressed negative perceptions of marijuana use. For 8th and 10th grade students, these changes replicate recent trends that began in the early 1990s. However, for seniors, this year's data indicate that the rate of increase of use has slowed and that attitudes are improving somewhat, with many differences in use and attitudes between 1995 and 1996 being non-statistically significant. Unless noted otherwise, all changes presented below are statistically significant.

Illicit Drug Use
  • Use of marijuana/hashish continued to climb, especially among 8th and 10th graders. Between 1995 and 1996, lifetime, past year, past month, and daily marijuana use increased among 8th and 10th graders, while only lifetime use increased among 12th graders. Since 1992 past year marijuana use has increased in all three grades and in virtually all demographic and geographic subdomains surveyed. (i.e., gender, census region, population density, and race/ethnicity). The only exception was no change among Hispanic Americans in 12th grade.
  • Driven in large part by the rise in marijuana, lifetime, past year, and past month use of any illicit drug increased among 8th and 10th graders.
  • Past month use of hallucinogens decreased among 12th graders between 1995 and 1996, as did past month use of LSD among 10th and 12th graders.
  • Lifetime use of cocaine in any form increased for 10th graders while past year use increased for 12th graders. Use of crack for all recency periods remain unchanged among all three grades.
  • Lifetime, past year, and past month use of tranquilizers increased for 8th graders while lifetime use increased for 10th graders.
  • Heroin use did not change among seniors, 10th, and 8th graders.
  • Use of stimulants for any recency period did not change among any grades.

Perceived Harmfulness and Availability
  • The percentage of 10th graders reporting "great risk" in trying marijuana once or twice or in smoking the drug occasionally decreased. Among 8th graders, the percent reporting "great risk" in regular marijuana use decreased from 73.0 percent in 1995 to 70.9 percent in 1996. The percent of seniors reporting "great risk" in regular marijuana use decreased steadily from 78.6 percent in 1991 to 60.8 percent in 1995, and remain unchanged at 59.9 percent in 1996.
  • The perceived risk (percentage reporting "great risk") of smoking a pack or more of cigarettes per day remain unchanged among all three grades.
  • The perceived risk of trying inhalants once or twice or using them regularly, increased among 8th and 10th graders.
  • The perceived risk of taking one or two drinks once or twice each weekend deceased for 8th graders and increased for 12th graders. Also the perceived risk of taking one or two drinks nearly every day decreased among 8th graders.
  • The percentage reporting that marijuana was "fairly easy" or "very easy" to get increased among 8th and 10th graders. The perceived availability of amphetamines and steroids decreased among seniors.

Alcohol Use
  • As in past years, alcohol continues to be used at unacceptably high levels. Notably, however, daily drinking and "being drunk" during the past month increased among 8th graders.

Cigarette Use
  • Between 1995 and 1996, past month cigarette use increased from 19.1 to 21.0 percent among 8th graders and from 27.9 to 30.4 percent among 10th graders. Daily smoking increased from 16.3 to 18.3 percent among 10th graders. Among subgroups in 10th grade, increases occurred for males and females, whites, and those with college plans.
  • Since 1991, past month smoking has increased from 14.3 to 21.0 percent for 8th graders, 20.8 to 30.4 percent for 10th graders, and 28.3 to 34.0 percent for 12th graders.
  • From 1995 to 1996, smoking _ pack or more per day increased among 8th and 10th graders.

Cannabinoid Receptor Gene (CNR1): Association with IV Drug Use David Comings at the City of Hope (Duarte, CA) and colleagues compared individuals who were homozygous for 5 or more triplet repeats (of AAT) in the cannabinoid receptor gene (CNR1) with individuals who were either heterozygous, or homozygous for less than 5 repeats. The sample was selected from an inpatient Addiction Treatment Unit (ATU) and hospital or university controls. While there was no greater frequency of homozygous > 5 repeat genes in controls versus ATU subjects, there was a significantly (nearly twice) greater number of these homozygotes among subjects in the ATU who took drugs intravenously. This difference prevailed regardless of the drug of choice: amphetamine, cocaine, or heroin. Using a factor analysis to combine diagnostic questions, the first two factors consisted of questions primarily associated with drug dependence (Factor 1) or alcohol dependence (Factor 2). Those homozygous for > 5 repeats had a significantly higher Factor 1 (drug dependency) score than the other genotypes, but there was no difference between the genotypes on the Factor 2 (alcohol dependence) score. Comings, D.E., Muhleman, D., Gade, R., Johnson, J. P., Verde, R., Saucer, G, MacMurray, J. Cannabinoid Receptor Gene (CNR1): Association with IV Drug Use, Molecular Psychiatry, In Press. In a related study, male subjects of the ATU with the homozygous > 5, > 5 genotype had significantly lower amplitudes of the P300 evoked potential, especially in the frontal lobe leads compared to the heterozygote (> 5, < 5) or < 5, <5 homozygote genotypes. Lowered P300 amplitudes have been associated with subjects with substance dependence or their off-spring. Johnson, J. P., Muhleman, D., MacMurray, J., Gade, R., Verde, R., Ask, M., Kelley, J., and Comings, D.E. Association between the Cannabinoid Receptor Gene (CNR1) and the P300 Event-related Potential. Molecular Psychiatry, In Press. The authors hypothesize that the varying lengths of the triplet repeats affects gene regulation and that the magnitude of the effect is dependent upon the length of the repeats. These studies report behavioral outcomes (greater IV drug use and lowered P300 amplitudes) for homozygotes with >5 repeats.

The Relationship Between Childhood Maltreatment and Delinquency This study analyzed data from the Rochester Youth Development Study to investigate the relationship between childhood maltreatment and later adolescent involvement in delinquency. A significant relationship was found between child maltreatment and later delinquency, even when controlling for other factors. It appears that more extensive maltreatment was related to higher rates of delinquency. The majority of maltreated youth however demonstrated resilience in terms of serious delinquency. The findings point to further research needs on which to base the design of interventions. Smith, C. and Thornberry, T.P. The Relationship Between Childhood Maltreatment and Adolescent Involvement in Delinquency. Criminology, 33(4), pp. 451-481, 1995.

Perception of Friends' Drug Use among Urban Schoolchildren Linked to Own Prior Use Relations between adolescents' substance use and perceptions of their friends' substance use were examined cross-sectionally and longitudinally in a predominantly African American school district. Students in the 4th and 5th grades were surveyed and tracked for 4 consecutive years. Cross-sectional samples included 3,073, 5,955, 7,701 and 6,616 students in years 1 to 4 respectively. The longitudinal sample included 1,802 students surveyed every year. Self-reported substance use of friends and classmates also was assessed. Perceived friends' substance use had a stronger association with the child's own prior substance use than with the friend's self reported substance use in every year. Perceived family use and classmates' self reported use also made independent contributions to regression models. Longitudinal structural equation analyses indicated that perceived friends' use is more likely to be a product of an adolescent's previous substance use than a precursor of subsequent substance use. Findings contradict prevailing theories on the influence of peers on substance use. Perceived use by peers instead derived from one's own prior use. Iannotti, R.J., Bush, P.J., and Weinfurt, K.P. Perception of Friends' Use of Alcohol, Cigarettes, and Marijuana among Urban Schoolchildren: A Longitudinal Analysis. Addictive Behaviors, 21(5), pp. 615-632, 1996.

Trends Among American Indian Youth Dr. Frederick Beauvais of Colorado State University reported that Indian youth residing on reservations continue to show very high rates of drug use compared to their non-Indian peers. Although overall drug use has decreased from its high levels of the 1970's and 1980's, heavy involvement with drugs is reported by about 20 percent of Indian adolescents, a proportion that has not changed since 1980. These findings are based on cross-sectional school survey data of 8th-12th grade Indian youth covering the 20 years from 1975 through 1994. The school survey is augmented by a special study of dropouts to permit adjustment of estimates to represent the total population of Indian youth. The investigator concludes that Indian youth, particularly dropouts, remain at high risk for drug use and abuse. Similar trends for these youth and their non-Indian counterparts suggest that prevention strategies effective with other youth can be effective with Indian youth. Beauvais, F. Trends in Drug Use Among American Indian Students and Dropouts, 1975-1994. American Journal of Public Health, 86(1), pp. 1594-1598, Nov., 1996.

Determinants of Drug Abuse in Urban Black Youth This study examined the role of cognitive efficacy, personal anomie, and general deviance in predicting substance use in a sample of urban black youth. The study also examined the reliability and construct validity of measurement of these three factors in adolescents. The findings underscore the primacy of deviance in predicting drug use for minority youth, and the need to incorporate affective influences into current interventions strategies. Scheier, L.M. and Botvin, G.J. Purpose of Life, Cognitive Efficacy, and General Deviance as Determinants of Drug Abuse in Urban Black Youth. Journal of Child & Adolescent Substance Abuse, 5(1), pp. 1-26, 1996.

Identifying High-Risk Youth: Prevalence and Patterns of Adolescent Drug Abuse Newcomb (1995) reviewed the literature on drug abuse epidemiology and etiology in regard to identifying youth at high risk. Data from both national and local samples were presented indicating disturbing upward trends in use of illicit drugs among teenagers. Numerous risk and protective factors were delineated as reflecting four biopsychosocial domains including biogenetic, intrapersonal, social, and socio-cultural influences. New analyses were presented that incorporated multiple risk and protective factors into cumulative indices and both the direct and moderating effects of these on drug use and abuse were evaluated. Newcomb extended this etiological approach to understanding drug use and abuse among ethnically-diverse teenagers. Both similarities and differences in risk and protection exposure and impact on drug use were emphasized. This information was discussed in regard to common versus unique approaches to drug abuse prevention among adolescents from ethnically-diverse backgrounds. In both chapters, drug use is characterized as an important aspect or symptom of general deviance that cannot be studied, predicted, or prevented in isolation from the fabric of other types of deviance. Newcomb, M.D. Identifying High-Risk Youth: Prevalence and Patterns of Adolescent Drug Abuse. In E. Rahdert and D. Czechowicz, (Eds.), Adolescent Drug Abuse: Clinical Assessment and Therapeutic Interventions, pp. 7-38, 1995. National Institute on Drug Abuse, Rockville, MD.

Alcohol Sensitivity and Smoking History in Men and Women Many studies have found genetic effects to contribute to alcoholism risk in both men and women. Based on preliminary evidence for shared genetic risk between smoking and drinking problems, a re-analysis of alcohol challenge data on 412 Australian twins was performed to explore the possibility that smoking may diminish or moderate the intoxicating effects of alcohol. The authors found history of smoking to be strongly associated with self-reported intoxication after alcohol challenge in women (women: r= -0.44 + 0.08; men: r= -0.21 + 0.08), comparable with self-reported average weekly consumption of alcohol, which was more strongly associated in men (women: r= -0.37 + 0.07; men: r= -0.54 + 0.06). Structural equation model fitting indicated a strong association between heavy drinking and smoking, but the association between smoking and post-alcohol intoxication remained even when the effects of heavy drinking were controlled for. These results prompt the question of whether smoking cigarettes directly influences the transition from moderate to excessive use of alcohol by diminishing feelings of alcohol intoxication. Madden, P.A.F., Heath, A.C., Starmer, G.A., Whitfield, J.B., and Martin, N.G. Alcoholism: Clinical and Experimental Research, 19(5), October, 1995.

Fatal Consequences of Cocaine and Opiate Use Cocaine, often with opiates (predominantly heroin) and ethanol, caused almost three-fourths of accidental fatal drug overdoses in New York City in 1990 through 1992. This study assessed all 1986 cases in that period using data collected in the Office of Chief Medical Examiner. This study excluded intentional (suicidal) fatal drug overdoses. Cocaine with opiates caused 752 (37.9%) deaths. Cocaine without opiates caused 629 (31.7%) deaths while opiates without cocaine caused 503 (25.3%) deaths. Drugs other than cocaine or opiates, predominantly benzodiazepines and antidepressants, caused 102 (5.1%) deaths. The highest cocaine overdose rates were found among African-American and Latino males. Rates of opiate overdose without cocaine did not differ in regard to race/ethnicity except for low rates among Asians. Males had higher overdose rates than women for all classes of drugs. The highest rates for cocaine and/or opiates were found among victims 35-44 years of age. The rates of overdose from cocaine and opiates increased from 1990-1992. There was a less pronounced but steady increase of opiate overdoses over that period of time. There was a marked increase of cocaine overdoses in 1991 followed by a slight decrease in 1992. The rates of overdoses from drugs other than cocaine or opiates showed no increase over time. Cocaine is the leading cause of accidental drug overdoses, unlike in the early 1980's when opiates prevailed as a cause of death. African-American and Latino males may be particularly susceptible to cocaine overdoses because of their exposure to crack in poor neighborhoods. This points to the urgency of targeting drug treatment and police interventions to these high risk areas. Tardiff, K., Marzuk, P.M., Leon, A.C., Hirsch, C.S., Stajic, M., Portera, L., Hartwell, N., Accidental Fatal Drug Overdoses in New York City: 1990-1992. The American Journal of Drug and Alcohol Abuse, 22 (3), 1996.

Reciprocal Relationships among Drug Use, Peers, and Beliefs This study examines the assumptions of interfactional theory which posits a reciprocal relationship among drug use, association with drug using peers, and beliefs about drug use. Five waves of longitudinal data from the Rochester Youth Development Study were analyzed. Results largely supported the hypotheses, although the effect from drug use to peer drug use was slightly larger than from peer use to drug use. The effects of beliefs on drug use was relatively weak although the two variables were reciprocally related. These findings have important implications for theory development and intervention strategies. Krohn, M.D., Lizotte, A.J., Thornberry, T.P., Smith, C., and McDowall, D. Reciprocal Causal Relationships among Drug Use, Peers, and Beliefs: A Five-wave Panel Model. Journal of Drug Issues, 26(2), pp. 405-428, 1996.

Substance Use and Suicide Attempts among Runaway and Homeless Youth Researchers at RTI examined how youth suicide attempts are associated with youth and familial substance use among a nationally representative sample of runaways and homeless youth (RHY) residing in shelters, and a multi-city, purposive sample of RHY found on the street. Analyses revealed that, after controlling for key demographic characteristics, youth who had used substances, (particularly sedatives, hallucinogens, and inhalants), were much more likely than those who had not used substances to have attempted suicide. In addition, after controlling for their own substance use, youth with family members who had used substances were twice as likely as those without such family members to have ever attempted suicide. This study suggests the importance of developing and focusing suicide prevention efforts on RHY known to have used substances and to have substance-using family members. Greene, J.M. and Ringwalt, C.L. Youth and Familial Substance Use's Association with Suicide Attempts among Runaway and Homeless Youth. Substance Use and Misuse, 31(8), pp. 1041-1058, 1996.

Immediate Impact of Thirty-Two Drug Abuse Prevention Activities Among Students at Continuation High Schools Continuation (i.e. alternative) versus comprehensive (i.e. regular) high schools form a natural demarcation of youth who are at relatively high or low risk for substance abuse in the State of California. Those teenagers who are unable to remain in the regular school system for reasons including substance use are transferred to a continuation high school. Generic comprehensive social influence drug abuse prevention activities are less likely to be effective for use with these at risk youth. Thus, both classroom and self-instruction (main mode of instruction at continuation high schools) versions of 16 activities derived from different theoretical sources were tested and ranked on immediate outcome variables. Students from six continuation high schools were provided with a pretest-activity-posttest "component study" protocol. The scores on perceived quality ratings were standardized and averaged to permit easy comparisons across lessons. While yielding similar knowledge changes, students who received the health educator led activity consistently reported higher scores on perceived quality. Social influence-oriented lessons, in general, were rated relatively low perceived quality. The present approach assisted in selection of the lessons with the greatest overall immediate impact. Sussman, S., Immediate Impact of Thirty-Two Drug Abuse Prevention Activities Among Students at Continuation High Schools. International Journal of the Addictions, In Press.

Substance Abuse Disorders Among Runaway and Homeless Youth This study used systematic sampling methods to recruit a sample of 432 homeless youth from both service and natural 'hang-out' sampling sites in Hollywood. The interview procedures relied on participants' self-reports. According to DSM-III criteria, 71% of the respondents were classified as having an alcohol and/or illicit drug abuse disorder. Age and gender were not significantly associated with risk of having an alcohol or drug abuse disorder. The cumulative length of time a youth spent without a consistent place to live was found to be positively associated with the risk for a diagnosis with either disorder. Kipke, M.D., Montgomery, S.B., Simon, T., Iverson, E.F. Substance Use & Misuse, 32, pp. 7-8, 1997.

Results indicated extremely high prevalences of mental health problems among homeless youth as compared with corresponding rates of mental health problems found among housed youth in previous studies. Prevalence of mental health problems differed by age and ethnicity. African-Americans were at lower risk of suicidal thoughts and self-injurious behavior than were youth of other ethnicities. Older youth and females were at increased risk of depressive symptoms and younger youth were at increased risk of self-injurious behavior. Risk factors for drug abuse disorder included ethnicity other than African-American, homelessness for one year or more, suicidality, self-injurious behavior, depressive symptoms, and low self-esteem. The study suggests the need for street-based and non-traditional mental health services targeted toward these youth. Unger, J.B., Kipke, M.D., Simon, T.R., Montgomery, S.B., and Johnson, C.J. Homeless Youth in Los Angeles: Prevalence of Mental Health Problems and the Relationships Between Mental Health and Substance Abuse Disorders. American Journal of Community Psychology, In Press.

The histories of the youths were examined in terms of violence, perpetration of violence and fear of violence in association with gender, ethnicity, age, and length of time homeless. Respondents reported having experienced a wide range of violent events and attacks. Levels of exposure to violence were similar for males and females. However, females were more likely to report having been sexually assaulted and less likely to have used a knife to attack or stab someone. There were differences between ethnic groups on some exposure measures. Exposure to violence was positively associated with cumulative length of time homeless, and inversely associated with age. Kipke, M.D., Montgomery, S., Simon T. and Iverson E. Homeless Youth and their Exposure to and Involvement in Violence while Living on the Streets. Journal of Adolescent Health, In Press.

Prevention of Steroid Use in Adolescent Athletes A randomized prospective trial involving 31 football teams in the Portland, Oregon area was recently conducted. Seven hundred two adolescent football players received seven weekly 50-minute class sessions delivered by coaches and student team leaders addressing anabolic androgenic steroid (AAS) effects, sports nutrition, and strength training alternatives to AAS use, drug refusal role play, and anti-AAS media messages. Seven weight room training sessions were taught by research staff. Compared with 804 players from control schools, the experimental subjects at 9- or 12-month follow-up had increased understanding of AAS effects, greater belief in personal vulnerability to the adverse consequences of AAS, improved drug refusal skills, less belief in AAS-promoting media messages, increased belief in the team as an information source, improved perception of athletic abilities and strength training self-efficacy, improved nutrition and exercise behaviors, and reduced intentions to use AAS. Effects of a Multi-Dimensional Anabolic Steroid Prevention Intervention. The Adolescent Training and Learning to Avoid Steroids (ATLAS) Program. Goldberg, L., Elliott, D., Clarke, D.N., MacKinnon, D.P., Moe, E., Zoref, L., Green, C., Wolf, S.L., Greffrath, E., Miller, D.J., and Lapin, A. JAMA, 276 (19), pp. 1-9, November 20th, 1996.

Effects of Chronic Cocaine Use on Physical Health The effects of chronic cocaine use by the late twenties on physical health by the mid thirties was studied in a longitudinal cohort from the general population. Among males, chronic cocaine use increased physical health problems, when controlling for possible confounding factors. Poor health also contributed to continued cocaine use. Chronic users experienced the most adverse consequences. Chen, K., Scheier, L.M., and Kandel, D.B. Effects of Chronic Cocaine Use on Physical Health: A Prospective Study in a General Population Sample. Drug and Alcohol Dependence, 43, pp. 23-37, 1996.

Polydrug Use and DSM-IV Alcohol Abuse and Dependence among Youth In a study of 176 adolescent drinkers with diagnoses of alcohol abuse (n=57) or alcohol dependence (n=61) or no alcohol diagnosis (n=58) based on a modified form of the Structured Clinical Interview for the DSM, researchers at CEDAR, the Center for Education and Drug Abuse Research at the University of Pittsburgh, investigated patterns of polydrug use, particularly combinations involving alcohol with other drugs. Lifetime histories of alcohol and other drug use were assessed, and frequency of use of specific alcohol-drug combinations was determined. Subjects with alcohol abuse and dependence diagnoses reported using greater numbers of illicit drugs than subjects without an alcohol diagnosis; recent polydrug use was higher among those with these diagnoses. Patterns of age of onset of psychoactive substance use followed those observed by prior researchers (i.e., alcohol, followed by marijuana, followed by other drugs). The most common alcohol-drug combination was alcohol with marijuana (reported by 58 percent of the sample), followed by alcohol with hallucinogens (16 percent). Frequency and extent of polydrug use increased with age and increased with increasing levels of behavioral under control and negative emotionality. Martin, C.S., Kaczynski, N.A., Maisto, S.A., and Tarter, R.E. Polydrug Use in Adolescent Drinkers with and without DSM-IV Alcohol Abuse and Dependence. Alcoholism: Clinical and Experimental Research, 20(6), pp. 1099-1108, 1996.

Nicotine Withdrawal In Women Associations between self-report symptom profiles for nicotine withdrawal, personality (TPQ, EPQ-R), lifetime history of psychopathology, and smoking history were examined in data obtained from 553 female adult Australian twins (246 regular smokers), aged 32-48, who had participated in a telephone interview survey that included lifetime assessments of smoking history, nicotine dependence and withdrawal. 202 respondents were from high-risk pairs where either the respondent or the respondent's cotwin had reported a lifetime history of alcohol dependence; 351 were from control pairs. Latent class analysis was used to identify subtypes ('classes') of smokers reporting similar withdrawal symptom profiles. Three major classes were identified which appeared to represent a continuum from mild to severe nicotine withdrawal. Smokers from the severe withdrawal class were best characterized by hands shaking and by the prominence of depressive features during withdrawal. There were marked increases in lifetime alcohol dependence rates as a function of severity class. In contrast, significantly elevated rates of major depression, conduct disorder, and anxiety disorder were observed only among smokers from the most severe withdrawal class. With the exception of Neuroticism, personality factors were more closely related to the initiation of regular smoking than to the development of withdrawal symptoms. Madden, P.A.F., Bucholz, K.K., Dinwiddie, S.H., Slutske, W.S., Bierut, L.J., Statham, D.J., Dunne, M.P., Martin, N.G., Heath, A.C., and Phil, D. Addictions, In Press.

Development of a School-Based Drug Abuse Prevention Curriculum for High-Risk Youths This paper presents the rationale for and the description of the empirical curriculum development process in Project Towards No Drug Abuse (Project TND). First, the target population is described, continuation high-school youths who are at high risk for drug abuse. The rationale for developing a classroom-based curriculum tailored for them is also provided. Second, a brief description is provided of state-of-the-art generic social influences drug abuse prevention programming, which has been found to be the most effective among young adolescents. There is a need to consider other prevention activities, particularly those that include motivational variables, to maximize prevention efforts among higher-risk youths. Third, five types of curriculum development studies are discussed that led to a curriculum that is being implemented with continuation high-school students at schools in five counties in southern California. Finally, the contents of the final curriculum product is provided which consist of motivation, skills-training, and decision-making components. Sussman, S. Development of a School-Based Drug Abuse Prevention Curriculum for High-Risk Youths. Journal of Psychoactive Drugs, Vol. 28(2), April-June 1996.

Key Qualities for Achieving a 96.6 Percent Follow-Up Rate in a Study of Drug Abusers. The St. Louis Effort to Reduce the Spread of AIDS Study (ERSA) aimed to reduce the spread of HIV among St. Louis' most vulnerable drug-using population while improving drug abuse treatment. As part of ERSA, researchers utilized a three-stage tracking strategy to follow out-of-treatment drug abusers for an 18-month longitudinal study. There were 479 ERSA subjects interviewed at baseline who were eligible for reinterview at the terminal 18-month interview; at follow-up, 454 persons had a complete interview (96.6%). The three-stage tracking strategy, consisting of phone tracking, systems tracking (using private and public databases, such as national credit information, social service data, and criminal justice data), and field tracking (visits by members of the research team to residents and "hang outs") -- coupled with patience, persistence, enthusiasm, creative team work, time, and money for remuneration (to the individual, the family, and as a bonus) -- were instrumental in achieving the 96.6% follow-up rate. Two particular qualities stood out from the others: persistence (not giving up) and creative team work. The researchers identified an experienced and enthusiastic staff who could work together as the most important factor for achieving the study goals. In addition, when the hard-to-reach respondents were compared on the basis of gender, race, age, education, psychiatric status, and employment status to those less difficult to find, only employment status was associated with being hard-to-reach. Cottler, L.B., Compton, W. M., Ben-Abdallah, A., et al. Achieving a 96.6 Percent Follow-Up Rate in a Longitudinal Study of Drug Abusers. Drug and Alcohol Dependence, 41: pp. 209-217, 1996.

A General Statistical Model for Detecting Complex Trait Loci Using Affected Relative Pairs in a Genome Search Family, twin, and adoption studies of substance abuse and dependency have demonstrated a significant role of genetic determinants. In the case of opioid dependency, using family studies and epidemiological data, the estimates of the heritability of opioid dependency is as high as 80 to 90%. These family studies justify the more detailed search of the human genome for the existence and exact location for susceptibility genes underlying opioid dependency. Such searches already have been undertaken for alcoholism. The search of the human genome for susceptibility genes is a difficult and expensive process that requires elaborate and powerful statistical methods to deal with the high dependency among DNA segments and the large number of such segments. Novel molecular techniques such as Genomic Mismatch Scanning (GMS) are emerging and promising to reduce the expense of the full genome search. But the statistical methods appropriate to the newer molecular techniques also must be developed. The current paper develops a general statistical model and test that can be used with traditional molecular techniques such as markers as well as the emerging GMS procedures. The model and test are designed to handle realistically complex genetic etiology and any mixture of relative types such as siblings, cousins, and grandparent-grandchildren, and also in the presence of phenocopies (i.e., misdiagnosis). Using affected pairs, the exact test controls for the elevated probability of false rejection of the null hypothesis when the entire genome is searched. Smalley, S.L., Woodward, J.A., Palmer, C.G.S. A General Statistical Model for Detecting Complex Trait Loci Using Affected Relative Pairs in a Genome Search. American Journal of Human Genetics, 58, pp. 844-860, 1996.

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