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Christian J Hopfer

Publications and source records attributed to Christian J Hopfer.

14 recordsLinked to original sources

Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine.

Nicotine addiction and alcohol dependence are highly comorbid disorders that are likely to share overlapping genetic components. We have examined two neuronal nicotinic receptor subunit genes (CHRNA4 and CHRNB2) for possible associations with nicotine and alcohol phenotypes, including measures of frequency of use and measures of initial subjective response in the period shortly after first using the drugs. The subjects were 1,068 ethnically diverse young adults participating in ongoing longitudinal studies of adolescent drug behaviors at the University of Colorado, representing both clinical and community samples. Analysis of six SNPs in the CHRNA4 gene provided modest support for an association with past 6 month use of alcohol in Caucasians (three SNPs with P < 0.08), but no evidence for an association with tobacco and CHRNA4 was detected. However, a SNP (rs2072658) located immediately upstream of CHRNB2 was associated with the initial subjective response to both alcohol and tobacco. This study provides the first evidence for association between the CHRNB2 gene and nicotine- and alcohol-related phenotypes, and suggests that polymorphisms in CHRNB2 may be important in mediating early responses to nicotine and alcohol.

Adolescent↗

Progression from marijuana use to daily smoking and nicotine dependence in a national sample of U.S. adolescents.

BACKGROUND: While it has been demonstrated that smoking cigarettes in adolescence increases the likelihood of progressing to marijuana use, few studies have considered the reverse scenario in which early use of cannabis leads to greater tobacco smoking. METHODS: Participants (n=5963), who had never smoked cigarettes daily by wave I of the National Longitudinal Study of Adolescent Health, were followed 6 years (waves I-III) from adolescence into young adulthood. Measures of marijuana use (lifetime use, monthly use, age at first use), as assessed at wave I within 12-16 (n=3712) and 17-21 (n=2251) year-olds, were separately modeled as predictors of three tobacco-related outcomes: (1) age at onset of daily cigarette smoking, (2) lifetime nicotine dependence, (3) current nicotine dependence. RESULTS: In the older cohort (17-21-year-olds at wave I), lifetime (>10 times) and past-month marijuana use at wave I were predictive of an earlier initiation into daily cigarette smoking and a greater likelihood of developing nicotine dependence by wave III. Furthermore, age at first use of cannabis was negatively associated with risk of nicotine dependence in the older, but not younger cohort. CONCLUSION: After controlling for baseline measures of tobacco smoking and other demographic risk factors, the use of marijuana in adolescence was modestly associated with daily cigarette smoking and nicotine dependence in young adulthood.

Adolescent↗

A genome-wide scan for loci influencing adolescent cannabis dependence symptoms: evidence for linkage on chromosomes 3 and 9.

OBJECTIVE: Cannabis is the most frequently abused illicit substance among adolescents and young adults. Genetic risk factors account for part of the variation in the development of cannabis dependence symptoms; however, no linkage studies have been performed for cannabis dependence symptoms. This study aimed to identify such loci. METHOD: Three hundred and twenty-four sibling pairs from 192 families were assessed for cannabis dependence symptoms. Probands (13-19 years of age) were recruited from consecutive admissions to substance abuse treatment facilities. The siblings of the probands ranged in age from 12 to 25 years. A community-based sample of 4843 adolescents and young adults was utilized to define an age- and sex-corrected index of cannabis dependence vulnerability. DSM-IV cannabis dependence symptoms were assessed in youth and their family members with the Composite International Diagnostic Instrument-Substance Abuse Module. Siblings and parents were genotyped for 374 microsatellite markers distributed across the 22 autosomes (average inter-marker distance=9.2cM). Cannabis dependence symptoms were analyzed using Merlin-regress, a regression-based method that is robust to sample selection. RESULTS: Evidence for suggestive linkage was found on chromosome 3q21 near marker D3S1267 (LOD=2.61), and on chromosome 9q34 near marker D9S1826 (LOD=2.57). CONCLUSIONS: This is the first reported linkage study of cannabis dependence symptoms. Other reports of linkage regions for illicit substance dependence have been reported near 3q21, suggesting that this region may contain a quantitative trait loci influencing cannabis dependence and other substance use disorders.

Adolescent↗

Cannabis receptor haplotype associated with fewer cannabis dependence symptoms in adolescents.

Cannabis is a major substance of abuse, and the gene encoding for the central cannabinoid receptor (CNR1) is a logical candidate gene for vulnerability toward developing symptoms of cannabis dependence. We studied four single-nucleotide polymorphisms (SNPs) in the CNR1 gene for association with having one or more symptoms of cannabis dependence in 541 adolescent subjects who had all tried cannabis five or more times. Cases (327) were defined as those who had tried marijuana and developed one or more symptoms, and controls (214) as those who had tried marijuana but developed no dependence symptoms. Cannabis dependence symptoms were assessed in these youth when they were 17 or older with the Composite International Diagnostic Interview--Substance Abuse Module. Univariate (single-marker) association tests demonstrated that SNP rs806380, located in intron 2 of the CNR1 gene, was significantly associated with developing one or more cannabis dependence symptoms, with the G allele having a protective effect (P < 0.02). This was consistent with the results of the global haplotype test (P < 0.01). One of the common haplotypes examined (present in 21% of the subjects) was significantly associated with a lower rate of having one or more cannabis dependence symptoms. Our findings provide evidence suggesting that a common CNR1 haplotype is associated with developing fewer cannabis dependence symptoms among adolescents who have experimented with cannabis.

Adolescent↗

Test of association between TaqIA A1 allele and alcohol use disorder phenotypes in a sample of adolescent patients with serious substance and behavioral problems.

UNLABELLED: Several studies have demonstrated a significant association between the A1 allele of the TaqIA polymorphism and various phenotypes of alcoholism, others have not, and two studies have shown the reversed association, where the A2 allele was associated with higher levels of alcohol consumption. We sought to test for an association between early onset (in childhood or adolescence) alcohol use disorders and the DRD2 TaqIA polymorphism and to resolve some of the hypothesized explanations for previous negative results, utilizing a larger sample than many previous studies. METHODS: We selected individuals with a lifetime alcohol abuse or dependence (n=239) diagnosis from a clinically ascertained sample of youth (ages 13-19) with serious conduct and substance problems (about 90% also met criteria for conduct disorder and a cannabis use disorder) and compared them with individuals without a lifetime alcohol use disorder diagnosis ascertained from (1) community adolescent controls (n=151), (2) siblings of patients (n=87) and (3) other adolescent patients (n=92). Cases were compared with each control group, separately, by genotype using the chi(2)-test. Using 78 adolescent patients with an alcohol use disorder where genotypic information was available for both parents, we conducted the transmission disequilibrium test (TDT). RESULTS: Case-control results were non-significant using the entire community control sample (chi(2)(2)=1.92; p=0.38) and when restricting the sample to Caucasians (chi(2)(2)=3.81; p=0.15) or Hispanics (chi(2)(2)=1.70; p=0.43). Case-control results using the other comparison groups and TDT results were also non-significant. DISCUSSION: We did not find support for an association between the TaqIA polymorphism and early onset alcohol use disorders.

Adolescent↗

Relationship between adolescent marijuana use and young adult illicit drug use.

: We examined three components of the "gateway theory" in relation to marijuana use: (1) whether adolescent marijuana use predicts young adult drug use, (2) whether this association persists when controlling for similar family background, (3) whether common genetic or environmental factors contribute to the association. The three components were tested in adolescents from the National Longitudinal Study of Adolescent Health assessed twice during adolescence and then re-interviewed 5 years later. Component 1 was tested in 18,286 subjects, component 2 in sibling pairs (n=360) discordant for marijuana use, and component 3 in a genetically informative sub-sample (n=4846). Marijuana use was defined as any use during adolescence, and drug use was defined as self-reported past year use of other illicit drugs besides marijuana. Marijuana users were twice as likely to use illicit drugs as young adults than non-users. Shared environmental factors mediated much of the relationship between adolescent marijuana use and young adult drug use. The association remained, however, even when controlling for familial environmental and other measured factors.

Adolescent↗

The family transmission of adolescent alcohol abuse and dependence.

OBJECTIVE: This study examines the familial transmission of alcohol abuse and dependence to adolescents. METHOD: Male adolescents recruited from a treatment program for substance problems, matched controls, and all available biological parents and siblings were assessed with a structured psychiatric interview assessing Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, based diagnoses of alcohol abuse and alcohol dependence. A total of 2,612 individuals from 911 families were interviewed. Structural equation modeling estimated tetrachoric correlations among family members, the proportion of variance in abuse and dependence attributable to parent-offspring transmission, and the effects of assortative mating and horizontal transmission among siblings. RESULTS: Tetrachoric correlations among siblings and parent-offspring ranged from .19 to .34 for abuse and dependence. Mother-father correlations were .14 and .37 for abuse and dependence, respectively. Modeling of familial transmission showed that 33% of the variance in abuse and 56% of the variance in dependence was accounted for by factors transmitted from parents. The effects of assortative mating could not be dropped from the abuse model without significant loss of model fit but could be dropped from the dependence model. Horizontal transmission among siblings could be dropped from both models without significant loss of fit. CONCLUSIONS: These results suggest that aggregation of alcohol abuse and alcohol dependence in families of male probands is significantly influenced by parental transmission of risk but is not reliably influenced by horizontal sibling effects such as sibling interactions or cohort effects. Spousal resemblance was found to be an important source of familial aggregation for alcohol abuse but not alcohol dependence.

Adolescent↗

Monoamine oxidase A (MAOA) and antisocial behaviors in the presence of childhood and adolescent maltreatment.

There is a robust relationship between the experience of maltreatment in childhood and later antisocial behaviors amongst adolescents and adults. Animal and human studies suggest that variation in monoamine oxidase A (MAOA) genotype may moderate the effects of maltreatment. Self-reported conduct problems and criminal convictions amongst sibling-pairs from the National Longitudinal Study of Adolescent Health were tested for association with reports of maltreatment before and after the age of 12. MAOA promoter polymorphisms were tested for possible moderation effects. Maltreatment predicted conduct problems and criminal convictions. MAOA genotype did not have a significant moderating effect in any of the six analyses that were conducted. We did not replicate a previous report that MAOA polymorphisms moderated the relationship between maltreatment and conduct problems. There was, however, a non-significant trend in the predicted direction. Additional studies will be needed before firm conclusions can be drawn about this hypothesized genotype-environment interaction.

Adolescent↗

Genetic influences on quantity of alcohol consumed by adolescents and young adults.

OBJECTIVE: To examine genetic and environmental influences on drinking in a nationally representative study of genetically informative adolescents followed into young adulthood. METHOD: The average quantity of alcohol used per drinking episode during the past year was analyzed in 4432 youth assessed during adolescence (mean age of 16) and then 1 and 6 years later. The variance of quantity of alcohol consumed was decomposed into three components: additive genetic (a2), shared environmental (c2), non-shared environmental (e2). Four candidate genes were tested for association. RESULTS: Wave 1 a2-0.52e2-0.48, Wave 2 a2-0.28e2-0.72, Wave 3 a2-0.30e2-0.70. Genetic correlations between Waves 1 and 2 were 0.85, Waves 1 and 3 were 0.34. The DAT1 440 allele was associated at Wave 1 (p=0.007). DRD2 TaqI A1/A2 was associated at Wave 3 (p=0.007). DRD4 and 5HTT were not associated. The DAT1 and DRD2 polymorphisms accounted for 3.1% and 2.0% of the variation, respectively. CONCLUSION: Genetic influence on drinking behavior was common in adolescents longitudinally assessed 1 year apart, but was less correlated between these adolescents and their assessment as young adults at a subsequent time point. Polymorphisms in genes of the dopaminergic system appear to influence variation in drinking behavior.

Adolescent↗

Review of twin and adoption studies of adolescent substance use.

OBJECTIVE: To review studies of adolescent substance use and abuse with genetically informative designs. METHOD: Twin and adoption studies of adolescent substance use were searched in Medline using keywords. RESULTS: Of 19 studies that used adolescent samples, 18 examined initiation or use of substances and 1 examined abuse. Of the 7 retrospective studies using adult samples, 6 examined problematic behaviors such as substance dependence. Genetic and shared environmental influences on adolescent substance use are moderated by the specific substance, age, gender, specific contexts, religiousness, and region. There is some evidence for a common genetic influence on substance use across substances. Genetic influences on adolescent substance use may act through an influence on disinhibited behavior. Shared environment contributed to adolescent substance use consistently across all adolescent samples and common shared environmental influences influenced initiation into tobacco and alcohol use. While parental alcohol use had a small influence on adolescent shared environment, sibling influences were substantial. CONCLUSIONS: Twin and adoption studies have increased our understanding of genetic and environmental influences on adolescent substance use and its initiation; however, more studies focusing on clinical syndromes of abuse and dependence are needed.

Adolescent↗

Family transmission of marijuana use, abuse, and dependence.

OBJECTIVE: To examine the familial aggregation of marijuana use, abuse, and dependence. METHOD: Adolescents recruited from residential and day treatment programs for youths with conduct and substance problems, matched controls, and all available family members were interviewed with structured research instruments. A total of 2,546 individuals from 781 families were interviewed. Risk ratios of relatives of clinical cases were calculated, compared with controls, for marijuana use, abuse, or dependence. Spousal, parent-offspring, and sibling correlations and the proportion of variance attributable to parent-offspring transmission were estimated using structural equation modeling. RESULTS: For all three measures, the risk ratios were elevated in the family members of clinical probands, with estimates ranging from 1.5 to 3.3. Spousal correlations ranged from 0.33 to 0.70. Parent-offspring correlations ranged from 0.17 to 0.30. Sibling correlations ranged from 0.34 to 0.44. The proportion of variance attributable to factors transmitted from parents to children ranged between 25% and 44%. CONCLUSIONS: Familial aggregation of marijuana use, abuse, and dependence is present for all three measures. The results suggest significant parent-offspring transmission of risk, sibling environmental influences, and assortative mating for all three levels of marijuana use.

Adolescent↗

Adolescent heroin use: a review of the descriptive and treatment literature.

The prevalence of heroin use is rising among young people. We reviewed descriptive and treatment studies of heroin-using youth. Medline and Psychinfo were searched with the following kewords: heroin or opiate; and adolescent or young or juvenile. Nine articles describing treatment and five articles describing clinical characteristics of youth with heroin use were reviewed. Descriptive studies of heroin-using youth demonstrate substantial polysubstance use and psychiatric comorbidity. The largest treatment study found that, of four different treatment modalities, methadone maintenance had the highest retention rate. For youth who stayed in treatment for at least 6 months, therapeutic communities or drug-free treatment resulted in better outcomes compared with methadone maintenance. No controlled treatment trials were found. Length of time in treatment, regardless of modality, was the best predictor of outcome. The rise of heroin use among adolescents and young adults calls for descriptive studies as well as controlled treatment studies.

Adolescent↗

Lesbian, gay, and bisexual homeless youth: an eight-city public health perspective.

This article reports on results of a one-day public health survey conducted in six states by homeless youth providers to measure and compare risk factors between lesbian, gay, and bisexual (LGB) homeless youth and non-LGB homeless youth. This article intends to inform the child welfare field on existing gaps in services and areas where more training and technical support is necessary in providing services to homeless LGB youth. The findings point to substantial differences within the homeless youth sample and demonstrate that in addition to the public health risks young people face merely by being homeless, the risks are exacerbated for those who self-identify as lesbian, gay, or bisexual. The article informs child welfare providers and policymakers about the substantial vulnerability of LGB youth beyond that of non-LGB homeless youth and the need to fund programming, training, technical assistance and further research to specifically respond to the complex needs of this population.

Adolescent↗