This study was conducted to test whether non-normative socialization mediates the association between transmissible risk measured in childhood and cannabis use disorder manifested by young adulthood, and whether the sequence of drug use initiation (“gateway”, i.e., consuming legal drugs before cannabis, or the reverse) increases accuracy of prediction of cannabis use disorder.
Sons of fathers with or without substance use disorders (SUD) related to illicit drugs were tracked from 10–12 to 22 years of age to model the association between transmissible risk for SUD, socialization (peer deviance), order of drug use initiation (“gateway” or reverse sequence), and development of cannabis use disorder. Path analysis was used to evaluate relationships among the variables.
Non-normative socialization mediates the association between transmissible risk measured during childhood and cannabis use disorder manifest by young adulthood. The sequence of drug use initiation did not contribute additional explanatory information to the model.
The order of drug use initiation does not play a substantial role in the etiology of cannabis use disorder.
gateway hypothesis; cannabis use; transmissible liability index (TLI)
Risk for substance use disorder is frequently transmitted across generations due to significant heritability.
This longitudinal study tests the hypothesis that initial exposure to cannabis in youths having high transmissible risk is a signal event promoting development of cannabis use disorder (CUD).
At age 22, 412 men were classified into three groups: (1) lifetime CUD, (2) cannabis use without CUD, and (3) no lifetime cannabis use. Transmissible risk, quantified on a continuous scale using the previously validated transmissible liability index (TLI), along with cannabis use and CUD were documented at 10–12, 12–14, 16, 19, and 22 years of age.
The CUD group scored higher on the TLI before they began cannabis use compared to the other two groups. In addition, a progressive increase in TLI severity was evinced by the CUD group beginning at the time of initiation of cannabis use whereas cannabis users who did not subsequently develop CUD exhibited a decline in transmissible risk following first exposure.
Initial use of cannabis potentiates development of CUD in youths who are at high transmissible risk but is inconsequential in youths having low risk. The practical ramifications of these results for prevention are discussed.
Transmissible Liability; Addiction; Cannabis use disorder; Longitudinal modeling
A neuropsychiatric study of individuals who underwent successful liver transplantation an average of 3 years previously was conducted to assess quality of life in terms of cognitive capacity and psychiatric status, as well as social and behavioral functioning. Compared with a control group of patients with Crohn’s disease, liver transplant patients did not differ on measures of intelligence, language, attention, concentration, spatial organization, memory, or learning. Performance on these diverse aspects of cognitive functioning was in the normal ranges for both groups when compared with normative or standardized test values. The control and liver transplant patients were not different from each other on measures of psychiatric status or social functioning; however, both groups exhibited some disruption of functioning in these two areas when contrasted with normative values. We conclude that relatively young individuals (mean age in this study, 27.8 years) do not exhibit debilitating long-term neuropsychiatric disability after liver transplantation, although some disturbance in social and psychiatric adjustment was observed.
Although much is known about the neuropsychological functioning of cirrhotic individuals with Laennec's (alcohol associated) cirrhosis, little is known about the neuropsychological functioning of individuals with nonalcoholic cirrhosis. In the present investigation, we have determined that individuals suffering from chronic nonalcoholic cirrhosis, despite the absence of clinical signs of hepatic encephalopathy, are impaired on neuropsychological tests that measure visuopractic capacity, visual scanning, and perceptual-motor speed. In contrast, intellectual, language, memory, attentional, motor, and learning abilities are intact. In comparison with a chronically ill control group of patients suffering from Crohn's disease, individuals with advanced nonalcoholic cirrhosis exhibit less emotional disturbance, but are more impaired in their daily activities. These findings indicate that individuals with nonalcoholic cirrhosis, even in the absence of overt clinical signs of encephalopathy, manifest neuropsychological impairments and experience significant disruption in the routines of everyday living.
Two competing concepts address the development of involvement with psychoactive substances: the “gateway hypothesis” (GH) and common liability to addiction (CLA).
The literature on theoretical foundations and empirical findings related to both concepts is reviewed.
The data suggest that drug use initiation sequencing, the core GH element, is variable and opportunistic rather than uniform and developmentally deterministic. The association between risks for use of different substances, if any, can be more readily explained by common underpinnings than by specific staging. In contrast, the CLA concept is grounded in genetic theory and supported by data identifying common sources of variation in the risk for specific addictions. This commonality has identifiable neurobiological substrate and plausible evolutionary explanations.
Whereas the “gateway” hypothesis does not specify mechanistic connections between “stages”, and does not extend to the risks for addictions, the concept of common liability to addictions incorporates sequencing of drug use initiation as well as extends to related addictions and their severity, provides a parsimonious explanation of substance use and addiction co-occurrence, and establishes a theoretical and empirical foundation to research in etiology, quantitative risk and severity measurement, as well as targeted non-drug-specific prevention and early intervention.
Drug dependence; Drug abuse; Genetics; Phenotype; Evolution
This article discusses human individuality within a lifespan developmental perspective. The practical application of an individual differences framework for diagnosis, prevention and treatment of addiction is described. A brief overview of the methods conducive to knowledge development within the rubric of person-centered medicine that are available to practitioners working in office and clinic settings concludes the discussion.
Addiction; development; etiology; person-centered medicine; prevention; risk; treatment
Toward meeting the need for a measure of individual differences in substance use disorder (SUD) liability that is grounded in the multifactorial model of SUD transmission, this investigation tested to what degree transmissible SUD risk is better measured using the continuous Transmissible Liability Index (TLI) (young adult version) compared to alternative contemporary clinical methods.
Data from 9,535 18- to 30-year-olds in the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions, a U.S. representative sample, were used to compute TLI scores and test hypotheses. Other variables were SUDs of each DSM-IV drug class, clinical predictors of SUD treatment outcomes, treatment seeking and usage, age of onset of SUDs and substance use (SU), and eligibility for SUD clinical trials.
TLI scores account for variation in SUD risk over and above parental lifetime SUD, conduct and antisocial personality disorder criteria and frequency of SU. SUD risk increases two- to four-fold per standard deviation increment in TLI scores. The TLI is associated with SUD treatment seeking and usage, younger age of onset of SU and SUD, and exclusion from traditional clinical trials of SUD treatment.
The TLI can identify persons with high versus low transmissible SUD risk, worse prognosis of SUD recovery and to whom extant SUD clinical trials results may not generalize. Recreating TLI scores in extant datasets facilitates etiology and applied research on the full range of transmissible SUD risk in development, treatment and recovery without obtaining new samples.
substance use disorders; transmissible risk; assessment; young adults; treatment outcomes
Elementary school-age child report instruments that do not require reading or interviews are lacking. In four samples, psychometric estimates for 5- to 9-year-olds were obtained for the Assessment of Liability and Exposure to Substance use and Antisocial behavior© (ALEXSA©), a child-report instrument that can be completed even by illiterate children. Invariance between minority groups vs Caucasians also was tested. Samples were: high-risk, low SES African-Americans (n=337), youth of varied ethnicities experiencing chronic stress (n=209), Mexican migrants in a reading remediation program (n=45), and U.S. twins (42 pairs) who were nearly all Caucasian. Validity criteria consisted of child-, parent-, teacher- and research evaluator-ratings on previously developed research and clinical instruments. Replicating results with older samples, ALEXSA factors had adequate or better reliabilities and demonstrated validity in all four studies. Ethnic invariance was found except for differences that were expected due to migrant's after-school program. In sum, psychometrics of the ALEXSA were supported for 5- to 9-year-olds of varied races/ethnicities, risk levels and academic skills.
Assessment; children; substance use; antisocial behavior; risk factors; validity; reliability
This study examined the contribution of transmissible risk, in conjunction with family and peer contextual factors during childhood and adolescence, on development of cannabis use disorder in adulthood.
The family high risk design was used to recruit proband fathers with and without substance use disorder and longitudinally track their sons from late childhood to adulthood.
The families were recruited under aegis of the Center for Education and Drug Abuse Research in Pittsburgh, Pennsylvania.
The oldest son in the family was studied at ages 10–12, 16, 19, and 22.
The transmissible liability index (TLI) (Vanyukov et al., 2009) along with measures of quality of parent child relationship, cooperative behavior at home, social attitudes, and peer milieu were administered to model the developmental pathway to cannabis use disorder.
Affiliation with socially deviant peers and harboring non-normative attitudes (age 16) mediate the association between transmissible risk for SUD (age 10–12) and use of illegal drugs (age 19) leading to cannabis use disorder (age 22).
Deviant socialization resulting from transmissible risk and poor parent-child relationship is integral to development of cannabis use disorder in young adulthood.
deviant socialization; cannabis use; transmissible liability index (TLI)
The factors that distinguish adolescent male and female substance abusers with and without legal problems were investigated.
Youths (N = 4,071) admitted for substance abuse treatment were administered the revised Drug Use Screening Inventory (DUSI-R) to measure severity of health, behavior, and social adjustment problems.
Legal problems were more frequent among boys; however, severity of disturbance was greater in girls on 9 of 10 scales. Substance abusing girls and boys with legal problems reported more severe behavior, substance abuse, family adjustment, and peer relationship problems than substance abusing peers without legal problems. Quality of peer relationship mediated the association of family dysfunction, substance abuse and behavior problems with legal problems in boys only.
Gender and legal status both need to be taken into account to potentiate treatment prognosis of substance abusing youths.
adolescents; substance abuse; treatment; legal problems; delinquency
This study determined the extent to which alcohol and marijuana use during adolescence mediates the relation between transmissible risk for substance use disorder (SUD) and lifetime number of different types of violent offenses.
The transmissible liability index was administered to 359 10-12 year old youths who were tracked to 22 years of age. Past year frequency of alcohol and marijuana consumption was longitudinally tracked to age 22 at which time lifetime violent offenses was recorded.
Rate of increase in marijuana use mediated the association between transmissible risk and lifetime number of different types of violent offenses. No association was found between past year frequency of alcohol use and violent offenses.
Prevention directed at lowering the psychological characteristics associated with transmissible risk for SUD may also reduce violent offending.
marijuana; violent offenses; alcohol; substance use disorder
Cognitive functioning in alcoholic cirrhotics before and 1 year following orthotopic liver transplantation was compared with age- and sex-matched normal subjects. The alcoholic group improved significantly following transplantation on tests measuring psychomotor, visuopractic and abstracting abilities whereas the performance of normal controls remained virtually unchanged. In contrast, memory capacity in alcoholics with cirrhosis did not statistically improve following successful transplantation. Further investigation, using more sophisticated measures of memory function, are required to determine whether memory deficits are either associated with alcohol neurotoxicity or an irreversible component of hepatic encephalopathy. These findings suggest that a reversible hepatic encephalopathy underlies many of the neuropsychologic deficits observed in cirrhotic alcoholics and can be ameliorated following successful liver transplantation.
Neuropsychologlc Deficits; Hepatic Encephalopathy; Alcoholic Cirrhosis; Liver Transplantation
Orthotopic liver transplantation is a clinical procedure that has been accepted widely as the treatment of choice for individuals with advanced chronic liver disease. As such, its application to the important clinical problem of alcoholic liver disease is inevitable. The arguments for and against liver transplantation for individuals with advanced alcoholic liver disease are presented.
To assess whether or not liver transplantation and subsequent immunosuppression with cyclosporine and prednisone affect ulcerative colitis symptomatology, we surveyed by questionnaire all 23 surviving patients with pretransplant colonoscopy-documented ulcerative colitis who were transplanted for primary sclerosing cholangitis between June 1982 and September 1985. At follow-up [89.8 ± 7.6 weeks (mean ± SEM], all six patients who had had asymptomatic colonoscopy-documented ulcerative colitis reported continued ulcerative colitis quiescence. Among the 17 patients who had had symptomatic colonoscopy-documented ulcerative colitis at time of liver transplantation, 88.2% reported improvement in overall ulcerative colitis severity (P < 0.001), with significant improvement in the frequency of bowel movements reported by 100%, in crampy abdominal pain by 87.5%, in bowel urgency by 75%), in the occurrence of pus or mucus in stool by 87.5%, in the incidence of ulcerative colitis flares by 81.8%, and in the number of days unable to function normally due to ulcerative colitis symptoms by 78.6%) (all at least P < 0.01). These data demonstrate that ulcerative colitis symptom severity significantly improves following liver transplantation with immunosuppression with cyclosporine and prednisone.
liver transplantation; ulcerative colitis; cyclosporine; sclerosing cholangitis; quality of life
Alcohol abuse is the most common cause of end-stage liver disease in the United States, but many transplant centers are unwilling to accept alcoholic patients because of their supposed potential for recidivism, poor compliance with the required immunosuppression regimen and resulting failure of the allograft. There is also concern that alcohol-induced injury in other organs will preclude a good result. From July 1, 1982, to April 30, 1988, 73 patients received orthotopic liver transplants at the University of Pittsburgh for end-stage alcoholic liver disease. Fifty-two (71%) of these were alive at 25 ± 9 mo (mean ± S.D.) after transplantation, when a phone survey of these patients, their wives/husbands, and their physicians was performed to evaluate their subsequent use of alcohol, current medical condition and employment. Data obtained were compared with those for nonalcoholic patients selected as transplant controls. The recidivism rate has been 11.5%, with most patients drinking only socially. Fifty-four percent of the survivors are employed, 21% classify themselves as homemakers and only 11 (21%) are unable to work. Twenty-one patients died after transplantation; the most frequent cause of death was sepsis (43%), and intraoperative death was the next most common cause (28.6%). These data demonstrate that alcoholic patients can be transplanted successfully and achieve good health not significantly different from that of individuals transplanted for other causes. Thus orthotopic liver transplantation is a therapeutic option that should be considered for individuals with end-stage alcoholic liver disease who desire such therapy.
Patient characteristics are important in the liver transplant (LTX) population because of proven associations between individual and environmental factors, treatment adherence, and health outcomes in general medical and other transplant (txp) populations.
The objective of this report is to determine generalizability of the sample to other LTX populations and to establish reliability of measures used to assess individual and environmental resources.
This is a cross sectional analysis of baseline data in a longitudinal study of adherence and health outcomes.
Ninety first-time adult LTX recipients at the University of Pittsburgh Medical Center completed assessments of socio-demographic, health history, psychosocial and environmental factors shortly after surgery; adherence and health outcomes are tracked throughout the study.
The UPMC cohort is older, less racially diverse, and contains more living donors than the national sample. Our sample is generally comparable to the UPMC cohort on pre-txp socio-demographic and clinical characteristics.
Comparable reliability/internal consistency on psychological measures is demonstrated between our sample and most published norms. The mean scores on all coping scales in our sample are higher than normative. Our subjects indicated a more negative perception of family environment and perceived relationships with their primary caregiver more positively than the normative group.
The generalizability of our sample to the parent population and reliability of individual and environmental measures reported here will enable us to examine relationships and predictive capability of patient and contextual resources on treatment adherence and health outcomes among liver transplant recipients.
liver; transplant; psycho-social; socio-demographic
Little is known about patients’ contribution to health outcomes after liver transplantation. Yet, in other transplant recipients, nonadherent behavior is directly related to the leading causes of morbidity and mortality in liver transplant recipients.
To examine patient and environmental factors in relation to all aspects of adherence to the posttransplantation regimen and health outcomes in the first 6 months after transplantation.
A descriptive analysis of individual and environmental factors in relation to adherence and health outcomes at 6 months after liver transplantation.
One hundred fifty-two adult liver transplant recipients at the University of Pittsburgh Medical Center.
Main Outcome Measures
Adherence to medication taking, appointment keeping, lifestyle changes, mood, quality of life, and clinical markers of liver function.
Nonadherence was prevalent (47% with appointments, 73% with medication); relapse to drug/alcohol use occurred among a few recipients (5.6%), all with a history of substance abuse before transplantation. Patterns of coping, decision making, attitude, and social support were correlated with adherence, clinical markers, and psychological function (r = 0.22–0.45). Avoidant coping, affective dysregulation, and caregiver support emerged as robust predictors of negative clinical and mental health outcomes (β = .224–.363).
This information about liver transplant recipients is important for researchers and clinicians. Researchers can develop guidelines by using stable but modifiable characteristics of patients to identify transplant candidates at risk of nonadherence. Such guidelines would enable clinicians to prepare patients better to manage the posttransplant regimen.
The role of testosterone in the development of behaviors presaging cannabis use and subsequently cannabis use disorder was investigated in a prospective study of 208 boys. It was theorized that adverse neighborhood correlates with testosterone level that in turn potentiates behaviors predisposing to cannabis consumption and subsequently diagnosis of cannabis use disorder.
Proportion of boarded-up dwellings in the 1990 census tract and testosterone level were recorded at baseline (age 10–12), followed by assessments of assaultiveness and testosterone level (age 12–14), social dominance/norm-violating behavior (age 16), cannabis use (age 19), and cannabis use disorder (age 22).
Percent of vacant dwellings correlates with testosterone level that in turn predicts assaultive behavior sequentially leading to social dominance/norm-violating behavior, cannabis use, and cannabis use disorder. Externalizing behaviors and cannabis use disorder are not directly predicted by neighborhood quality.
Elevated testosterone level intermediates the association between neighborhood adversity and aggressive socially deviant behaviors presaging cannabis use and cannabis use disorder.
substance abuse; cannabis; marijuana; etiology; neighborhood; hormones
This prospective investigation examined the contribution of neighborhood context and neurobehavior disinhibition to the association between substance use disorder (SUD) in parents and cannabis use disorder in their sons. It was hypothesized that both neighborhood context and son’s neurobehavior disinhibition mediate this association. Two hundred and sixteen boys were tracked from ages 10–12 to age 22. The extent to which neighborhood context and neurobehavior disinhibition mediate the association between parental SUD and son’s cannabis use disorder was evaluated using structural equation modeling. The best fitting model positioned neighborhood context and neurobehavior disinhibition as mediators of the association between parental SUD and cannabis use disorder in sons. Neurobehavior disinhibition also was a mediator of the association between neighborhood context and son’s cannabis use. The implications of this pattern of association between parental SUD, neighborhood context and individual risk for SUD for improving prevention are discussed.
Cannabis; Disinhibition; Neighborhood; Substance use disorder; Familial transmission; Structural equations modeling
Individual and contextual factors jointly participate in the onset and progression of substance abuse; however, the pattern of their relationship in males and females has not been systematically studied.
Male and female children and adolescents were compared to determine the relative influence of individual susceptibility (neurobehavior disinhibition or ND) and social environment (deviancy in peers) on use of illegal drugs.
Boys (N = 380) and girls (N = 127) were prospectively tracked from age 10–12 to age 16 to delineate the role of ND and peer deviancy on use of illegal drugs.
Girls exhibited lower ND scores than boys in childhood and were less inclined to affiliate with deviant peers. These differences were reduced or disappeared by mid-adolescence. In boys only, peer deviancy in childhood mediated the association between ND and illegal drug use at age 16. In both genders, peer deviancy in mid-adolescence mediated ND and substance abuse at age 16.
Individual and contextual risk factors promoting substance abuse are more salient at a younger age in boys compared to girls.
These results point to the need for earlier screening and intervention for boys.
Adolescence; gender; illegal drug involvement; neurobehavior disinhibition; peer deviancy
This investigation examined mediators of the longitudinal relation between negative affectivity and the development of problematic drinking behavior in adolescent boys and girls. In the present study, 499 early adolescents completed inventories of negative affectivity, attitudes toward delinquency, personal delinquency, and affiliation with delinquent peers. Positive attitudes toward delinquency emerged as the most consistent mediator and strongly predicted drinking frequency in various situations. Compared with personal delinquency, both attitudes toward delinquency and peer delinquency were superior predictors of affect-related drinking. Our results also demonstrated that positive attitudes toward delinquency mediated the relation between negative affectivity and later development of an alcohol use disorder. These findings suggest that a proneness to unpleasant affect impacts adolescent drinking by heightening risk for general rejection of normative behavior, rather than by increasing drinking as a means of managing affect. The importance and implications of testing delinquency variables together in the same model are discussed.
adolescent; alcohol; delinquency; negative affectivity
People in Appalachia experience some of the worst oral health in the United States. To develop effective intervention and prevention strategies in Appalachia, we must understand the complex relationships among the contributing factors and how they affect the etiology of oral diseases. To date, no such comprehensive analysis has been conducted. This report summarizes the characteristics of the sample and describes the protocol of a study determining contributions of individual, family, and community factors to oral diseases in Appalachian children and their relatives.
Families participated in a comprehensive assessment protocol involving interviews, questionnaires, a clinical oral health assessment, a microbiological assessment, and collection of DNA. The design of the study is cross-sectional.
Due to its multilevel design and large, family-based sample, this study has the potential to greatly advance our understanding of factors that contribute to oral health in Appalachian children.
psychotic disorders, addictive behaviour, molecular biology
The inability to quantify the risk for disorders, such as substance use disorders (SUD), hinders etiology research and development of targeted intervention. Based on the concept of common transmissible liability to SUD related to illicit drugs, a method enabling quantification of this latent trait has been developed, utilizing high-risk design and item response theory. This study examined properties of a SUD transmissible liability index (TLI) derived using this method. Sons of males with or without SUD were studied longitudinally from preadolescence to young adulthood. The properties of TLI, including its psychometric characteristics, longitudinal risk assessment and ethnic variation, were examined. A pilot twin study was conducted to analyze the composition of TLI’s phenotypic variance. The data suggest that TLI has concurrent, incremental, predictive and discriminant validity, as well as ethnic differences. The data suggest a high heritability of the index in males. The results suggest applicability of the method for genetic and other etiology-related research, and for evaluation of individual risk.
Addiction; Phenotype; IRT; Ethnicity; Race; Transmissibility