Research has shown involvement of hormones of the hypothalamic pituitary adrenal (HPA) axis and hypothalamic pituitary gonadal (HPG) axis in the regulation of behaviors that also contribute to SUD risk and its intergenerational transmission. Neighborhood environment has also been shown to relate to hormones of these two neuroendocrine systems and behaviors associated with SUD liability. Accordingly, it was hypothesized that 1) parental SUD severity and neighborhood quality correlate with activity of the HPG axis (testosterone level) and HPA axis (cortisol stability), and 2) transmissible risk during childhood mediates these hormone variables on development of SUD measured in adulthood.
Transmissible risk for SUD measured by the Transmissible Liability Index (TLI; Vanyukov et al., 2009) along with saliva cortisol and plasma testosterone were prospectively measured in boys at ages 10-12 and 16. Neighborhood quality was measured using a composite score encompassing indicators of residential instability and economic disadvantage. SUD was assessed at age 22.
Neither hormone variable cross-sectionally correlated with transmissible risk measured at ages 10-12 and 16. However, the TLI at age 10-12 predicted testosterone level and cortisol stability at age 16. Moreover, testosterone level, correlated with cortisol stability at age 16, predicted SUD at age 22.
HPA and HPG axes activity do not underlie variation in TLI, however, high transmissible risk in childhood predicts neuroendocrine system activity presaging development of SUD.
addiction; vulnerability; genetics; androgen; stress hormone; etiology
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)
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)
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.
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
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 study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10-12) and development of substance use disorder (SUD) in adulthood (age 22).
The Youth Attachment to Parents Scale (YAPS) was developed in 10-12 year old boys and girls (N = 694) at baseline residing in western Pennsylvania. Psychological dysregulation was measured by the neurobehavior disinhibition trait. Substance use was assessed at ages 10-12, 12-14, 16 and 19. SUD was diagnosed at age 22 using the Structured Clinical Interview for DSM Disorders. The mediation of parent-child attachment and SUD by neurobehavior disinhibition was tested separately for mothers and fathers while controlling for baseline substance use.
Psychological dysregulation mediates the association between attachment to mothers and SUD, and partially mediates the association between attachment to fathers and SUD. Significant mediation effects remains after controlling for baseline substance use.
Optimal prevention of SUD should include ameliorating both psychological dysregulation predisposing to SUD and quality of the parent-child relationship.
Parent-child attachment; substance use disorder; psychological dysregulation
This longitudinal study tested the hypothesis that neurobehavioral disinhibition (ND) in childhood, mediated by alcohol use, portends risky sexual behavior (number of sexual partners) in mid-adolescence.
Participants were 410 adolescent boys. Neurobehavioral disinhibition was assessed at 11.3 years of age. Frequency and quantity of alcohol use on a typical drinking occasion were assessed at 13.4 years of age at first follow-up and sexual behavior at 16.0 years at second follow-up.
Quantity of alcohol consumed on a typical drinking occasion, but not frequency of alcohol use, mediated the relation between ND and number of sexual partners.
These findings indicate that number of sexual partners in mid-adolescence is predicted by individual differences in boys’ psychological self-regulation during childhood and moderate alcohol consumption in early adolescence, and that ND may be a potential target for multi-outcome public health interventions.
Neurobehavioral Disinhibition; Sexual Risk Taking; Alcohol Use; Boys
The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms.
In 757 subjects, we performed association analysis between 1536 single nucleotide polymorphisms (SNPs) in 106 candidate genes and a drug use disorder diagnosis (DUD).
Associations (p ≤ .0008) were detected with three SNPs in the arginine vasopressin 1A receptor gene, AVPR1A, with a gene-wise p value of 3 × 10−5. Bioinformatic evidence points to a role for rs11174811 (microRNA binding site disruption) in AVPR1A function. Based on literature implicating AVPR1A in social bonding, we tested spousal satisfaction as a mediator of the association of rs11174811 with the DUD. Spousal satisfaction was significantly associated with DUD in males (p <.0001). The functional AVPR1A SNP, rs11174811, was associated with spousal satisfaction in males (p = .007). Spousal satisfaction was a significant mediator of the relationship between rs11174811 and DUD. We also present replication of the association in males between rs11174811 and substance use in one clinically ascertained (n = 1399) and one epidemiologic sample (n = 2231). The direction of the association is consistent across the clinically-ascertained samples but reversed in the epidemiologic sample. Lastly, we found a significant impact of rs11174811 genotype on AVPR1A expression in a postmortem brain sample.
The findings of this study call for expansion of research into the role of the arginine vasopressin and other neuropeptide system variation in DUD liability.
Addiction; alcoholism; gene systems; genetic association; social relationships; vasopressin
Knowledge of where substance use and other such behavioral problems frequently occur has aided policing, public health, and urban planning strategies to reduce such behaviors. Identifying locales characterized by high childhood neurobehavioral disinhibition (ND), a strong predictor of substance use and consequent disorder (SUD), may likewise improve prevention efforts.
The distribution of ND in 10–12-year olds was mapped to metropolitan Pittsburgh, PA, and tested for clustering within locales.
The 738 participating families represented the population in terms of economic status, race, and population distribution. ND was measured using indicators of executive cognitive function, emotion regulation, and behavior control. Innovative geospatial analyzes statistically tested clustering of ND within locales while accounting for geographic barriers (large rivers, major highways), parental SUD severity, and neighborhood quality.
Clustering of youth with high and low ND occurred in specific locales. Accounting for geographic barriers better delineated where high ND is concentrated, areas which also tended to be characterized by greater parental SUD severity and poorer neighborhood quality.
Conclusions and Significance
Offering programs that have been demonstrated to improve inhibitory control in locales where youth have high ND on average may reduce youth risk for SUD and other problem behaviors. As demonstrated by the present results, geospatial analysis of youth risk factors, frequently used in community coalition strategies, may be improved with greater statistical and measurement rigor.
disinhibition; children; geospatial analysis; substance use
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
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
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
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
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.
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.
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