Biomedical subjects

Robin P Corley

Publications and source records attributed to Robin P Corley.

At least 19 recordsLinked to original sources

PubMed2026

Prediction of alcohol consumption: The role of genetics, impulsivity, and sensation seeking from adolescence to adulthood.

BACKGROUND: There are well-known phenotypic and genetic associations among impulsivity, sensation seeking (SS), and alcohol consumption, but whether they vary between adolescence and early adulthood remains unclear. PURPOSE/HYPOTHESES: We hypothesized that adolescent alcohol consumption would be better predicted by polygenic indices (PGIs) of impulsivity and SS than PGIs of adult alcohol consumption (drinks per week; DPW), but that the reverse would be observed in young adulthood (i.e., stronger associations for DPW PGIs). METHODS: N = 733-754 twins of European genetic ancestry from the Colorado Longitudinal Twin Study were assessed at age 17 and/or 23 years using structural equation modeling. RESULTS: The SS PGIs were associated with alcohol consumption in adolescence (β=0.16), whereas DPW PGIs were associated with alcohol consumption in early adulthood (β=0.15). Additionally, phenotypic measures of impulsivity and SS are associated with alcohol consumption at both ages (β=.13-.21) and mediated some PGI-alcohol associations. DISCUSSION: These findings suggest that genetic influences on alcohol consumption change from adolescence to early adulthood, with genetic influences on sensation seeking most relevant to alcohol consumption in adolescence.

Humans↗

PubMed2007

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine oxidase A genotype.

BACKGROUND: A functional promoter polymorphism in monoamine oxidase A (MAOA) has been implicated as a moderating factor in the relationship between childhood maltreatment and later adolescent and adult antisocial behavior. Despite wide interest in this hypothesis, results remain mixed from the few attempts at replication. METHODS: Regression-based analyses were conducted to test for a genotype-environment interaction using self-reported physical abuse and MAOA genotype to predict later antisocial behavior and arrests for violence by participants in the National Youth Survey Family Study. We also examined the interaction using a measure of violent victimization. The analysis sample included 277 Caucasian male respondents, aged 11-15 in 1976, who provided buccal swab DNA samples and who were successfully genotyped for the variable number tandem repeat (VNTR) in the MAOA promoter using polymerase chain reaction. RESULTS: Maltreatment by a parent during adolescence was a risk factor for adolescent and adult antisocial and violence related behavioral problems. Tests for the main effect of MAOA and a MAOA-maltreatment interaction were nonsignificant. Similar results were obtained using the measure of adolescent violent victimization. CONCLUSIONS: Findings from this general population sample could not confirm the hypothesis that MAOA moderates the relationship between adolescent maltreatment and adolescent or adult antisocial behavior.

Adolescent↗

PubMed2006

The role of conduct disorder in explaining the comorbidity between alcohol and illicit drug dependence in adolescence.

BACKGROUND: Conduct disorder (CD), alcohol dependence (AD), and illicit drug dependence (IDD) frequently co-occur. This paper describes the result of an investigation of the extent to which comorbid alcohol and illicit drug dependence in adolescents are explained by etiological factors in common with conduct disorder. METHODS: Participants were 645 MZ twin pairs, 702 DZ twin pairs, 429 biological sibling pairs, and 96 adoptive sibling pairs, aged 12-18 years, from a community based sample. Conduct disorder was measured using the Diagnostic Interview Schedule for Children-IV. Alcohol and illicit drug dependence were assessed using the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). For each outcome, subjects were categorized into those with no symptoms, those with one or more symptoms but no diagnosis, and those with a diagnosis. RESULTS: The heritability estimates for CD, AD, and IDD were 58, 66, and 36%, respectively. The genetic correlation between AD and IDD was partially explained by the genetic risk they both share with conduct disorder. CONCLUSIONS: We conclude that conduct disorder in adolescents explains, in part, the co-occurrence of alcohol and illicit drug dependence. Specifically, the genetic contribution to their covariation is explained partially by the genetic contribution in common with conduct disorder.

Adolescent↗

PubMed2006

Genetic and environmental vulnerabilities underlying adolescent substance use and problem use: general or specific?

Are genetic and environmental risks for adolescent substance use specific to individual substances or general across substance classes? We examined this question in 645 monozygotic twin pairs, 702 dizygotic twin pairs, 429 biological sibling pairs, and 96 adoptive (biologically unrelated) sibling pairs ascertained from community-based samples, and ranging in age from 12 to 18 years. Substance use patterns and symptoms were assessed using structured psychiatric interviews. Biometrical model fitting was carried out using age- and sex-specific thresholds for (a) repeated use and (b) problem use, defined as one or more DSM-IV symptoms of abuse or dependence. We hypothesized that problem use would be more heritable than use in adolescence, and that both genetic and environmental risks underlying tobacco, alcohol, and marijuana use and problem use would be significantly correlated. Results of univariate analyses suggested significant heritable factors for use and problem use for all substances with the exception of alcohol use. Shared environmental factors were important in all cases and special twin environmental factors were significant for tobacco use, tobacco problem use, and alcohol use. Multivariate analyses yielded significant genetic correlations between each of the substances (for both levels studied), and significant shared environmental correlations among use variables only. Our results suggest that tobacco, alcohol, and marijuana problem use are mediated by common genetic influences, but shared environmental influences may be more substance-specific for problem use.

Adolescent↗

PubMed2006

Comorbidity between alcohol dependence and illicit drug dependence in adolescents with antisocial behavior and matched controls.

BACKGROUND: Knowledge regarding the causes of comorbidity among substance use disorders can have significant impact on future research examining the etiology of these disorders. Unfortunately, the conclusions of past studies examining the comorbidity among substance use disorders are conflicting; some studies emphasize familial influences common to multiple substances, while others emphasize substance-specific influences. Discrepancies in results may reflect different analytical approaches or differences in the samples. Here, we examine the causes of comorbidity between alcohol dependence and illicit drug dependence in adolescents. METHODS: We ascertained a clinical sample of adolescents treated for antisocial behavior and substance use disorders and their siblings and a matched control sample. A model fitting approach was used to test 13 alternative hypotheses for the causes of comorbidity. RESULTS: The best supported hypothesis for the comorbidity between alcohol dependence and illicit drug dependence was a model hypothesizing that comorbid disorders are alternate forms of a single underlying liability. The next best fitting models were two of the correlated liabilities models (correlated risk factors and reciprocal causation). DISCUSSION: The results suggest that the best hypotheses explaining the comorbidity between alcohol and illicit drug dependence in adolescents are that alcohol dependence and illicit drug dependence are manifestations of a single general liability to develop substance dependence or that there are separate liabilities that are highly correlated.

Adolescent↗

PubMed2006

Not all executive functions are related to intelligence.

Accumulating evidence suggests that executive functions (EFs) are related to intelligence, despite neuropsychological results initially considered evidence of no such relation. However, findings that EFs are not unitary raise the issue of how intelligence relates to different EFs. This study examined the relations of fluid and crystallized intelligence and Wechsler Adult Intelligence Scale IQ to three separable EFs--inhibiting prepotent responses (inhibiting), shifting mental sets (shifting), and updating working memory (updating)--in young adults. Updating was highly correlated with the intelligence measures, but inhibiting and shifting were not. Furthermore, in structural equation models controlling for the inter-EF correlations, updating remained strongly related to intelligence, but the relations of inhibiting and shifting to intelligence were small and not significant. The results indicate that intelligence measures differentially relate to these three EFs, suggesting that current intelligence measures do not equally assess a wide range of executive control abilities likely required for many "intelligent" behaviors.

Adult↗

PubMed2006

Interaction between MAO-A genotype and maltreatment in the risk for conduct disorder: failure to confirm in adolescent patients.

OBJECTIVE: Childhood maltreatment is a potent risk factor for subsequent aggressive and criminal behavior. A recent study suggested that the relationship between maltreatment and antisocial behavior may be moderated by a genetic vulnerability conferred by a functional polymorphism in the MAO-A gene. The authors investigated whether these findings would generalize to a clinical cohort of adolescents, examining whether there was a stronger association between maltreatment and conduct disorder severity in patients carrying the low MAO-A activity allele. METHOD: Male adolescent patients (N=247) entering residential or intensive day treatment for persistent conduct and substance use problems were examined. Conduct disorder severity was indexed by a lifetime count of DSM-IV criteria obtained through structured psychiatric interviews. Maltreatment scores were derived from summing neglect and abuse events reported to have occurred before age 11. RESULTS: Neglect, verbal/psychological abuse, physical abuse, and sexual abuse were prevalent among patients. Although level of maltreatment and lifetime conduct disorder symptoms were significantly correlated, no genetic-environmental interaction with genotype for maltreatment was found. CONCLUSION: The results of the current study do not support the hypothesis that a polymorphism in the gene encoding MAO-A contributes to the genetic risk for conduct disorder.

Adolescent↗

PubMed2006

Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence.

Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview--Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

Adolescent↗

PubMed2005

A genome-wide search for quantitative trait Loci that influence antisocial drug dependence in adolescence.

BACKGROUND: Among adolescents, externalizing problem behavior and substance use disorders are often comorbid. Familial influences, including shared genetic risk factors, may account for part of this comorbidity. Previously we reported 2 chromosomal regions (3q24-3q25 and 9q34) likely to contain genes that influence substance dependence vulnerability (DV) in adolescence. OBJECTIVES: To identify quantitative trait loci (QTLs) that influence externalizing problem behavior in adolescence and to determine whether any identified QTL overlap chromosomal regions that influence DV. DESIGN: Regression-based QTL mapping procedures designed for selected sibling pair samples. SETTING: Patient probands were drawn from consecutive admissions to residential and outpatient (milieu-type) treatment facilities for substance abuse and delinquency operated by the University of Colorado; most of these patients were referred for treatment by juvenile justice or social service agencies. PATIENTS: A total of 249 proband-sibling pairs from 191 families were selected for the study. Patient probands were 13 to 19 years of age; siblings of the probands ranged in age from 12 to 25 years. MAIN OUTCOME MEASURES: A community-based sample of 4493 adolescents and young adults was used to define clinically significant, heritable, age- and sex-normed indexes of DV, conduct disorder symptoms (CDS), and a composite index of antisocial substance dependence (DV + CDS). Siblings and parents were genotyped for 374 microsatellite markers distributed across the 22 autosomes (mean intermarker distance, 9.2 centimorgans). RESULTS: For both DV and CDS, there was evidence of linkage to the same region on chromosome 9q34, as well as to 3q24-3q25 for DV, and a novel region on chromosome 17q12 for CDS. Our composite index (DV + CDS) yielded the strongest evidence for linkage (logarithm of odds = 2.65) to the chromosome 9q34 region. CONCLUSION: These results provide the first evidence of a potential molecular genetic basis for the comorbidity between DV and antisocial behavior.

Adolescent↗

PubMed2005

Testing hypotheses regarding the causes of comorbidity: examining the underlying deficits of comorbid disorders.

The authors examined the validity of a method commonly used to test alternative hypotheses regarding the causes of comorbidity: the examination of underlying deficits of comorbid disorders. The authors simulated data in which the true causes of comorbidity were known, then compared the patterns of underlying deficits of the comorbid disorders found in the simulated data with the predicted results. The method of examining the underlying deficits of comorbid disorders could distinguish between several comorbidity models, including those that could not be distinguished well using other methods. The ability to distinguish the correct model decreased as the sample size and the correlation between the underlying deficits and the symptom scores decreased, suggesting that the issue of power should be considered carefully.

Adult↗

PubMed2005

Personality correlates of heroic rescue during the holocaust.

This study investigated the extent to which personality variables can be used to discriminate non-Jewish heroes of the Holocaust from bystanders and from a comparison group of prewar European immigrants who left their countries of origin prior to World War II. Eighty verified rescuers, 73 bystanders, and 43 immigrants were administered measures of locus of control, autonomy, risk taking, social responsibility, tolerance/authoritarianism, empathy, and altruistic moral reasoning. A three-group discriminant function analysis was able to correctly classify 80.2% of the sample by a combination of personality and demographic variables. When the bystanders and immigrants, who differed very little from each other, were grouped together and compared to the rescuers, the personality variables alone correctly classified 93.1% of the sample. Implications regarding the relationship between personality and altruistic behavior, as well as suggestions for future research are discussed.

Aged↗

PubMed2005

Genetic and environmental influences on conduct disorder: symptom, domain and full-scale analyses.

BACKGROUND: We used variable threshold models which accounted for age and gender differences to investigate the genetic and environmental influences on DSM-IV conduct disorder (CD) at the level of symptoms, aggressive versus non-aggressive domains, and full-scale. METHOD: A community sample of 1100 twin pairs (age 11-18) was interviewed using the Diagnostic Interview Schedule for Children. RESULTS: Behavior genetic model fitting suggested that genetic and environmental influences on individual symptoms varied by symptom. The best-fitting models for aggressive and non-aggressive domains, and full-scale CD included additive genetic effects and unique environmental effects only (AE models). These effects could be constrained across age cohorts and sex. The results suggest that using models that incorporate age- and gender-appropriate thresholds specific to each subject we can account for prevalence differences between cohorts. Heritability estimates were .49, .55 and .53 for the aggressive domain, non-aggressive domain, and full-scales, respectively. These results are in contrast to previous research on antisocial behavior measured with the CBCL reporting higher heritability for aggressive versus non-aggressive domains. CONCLUSIONS: Results suggest that individual symptoms of CD may be differentially heritable. Additionally, CD assessed using DSM-IV criteria may show differing patterns of heritability compared with estimates obtained for other measures of antisocial behavior such as the CBCL.

Adolescent↗

PubMed2004

The validity of the Neale and Kendler model-fitting approach in examining the etiology of comorbidity.

Given that knowledge regarding the etiology of comorbidity between disorders can have a significant impact on research regarding the classification, treatment, and etiology of the disorders, the ability to reject incorrect hypotheses regarding the causes of comorbidity is very important. A simulation study was conducted to assess the validity of the Neale and Kendler (1995) model-fitting approach in examining the etiology of comorbidity between two disorders. First, data were simulated under the assumptions of the 13 alternative comorbidity models described by Neale and Kendler. Second, model-fitting analyses testing the comorbidity models were conducted on the simulated datasets. Thirteen sets of data with varying model parameters were simulated to test Neale and Kendler's assertion that their model-fitting approach is appropriate across a range of potential prevalences and degrees of familiality. The validity of the model-fitting approach in examining unselected twin data and a combination of selected family data and unselected family data was explored. The model-fitting approach successfully discriminated several classes of comorbidity models, although discrimination between models within classes of related models was less accurate. Results suggest that the model-fitting approach can be a useful tool in examining the etiology of the comorbidity between disorders if the caveats of the present study's results are considered carefully. As predicted by Neale and Kendler, variations in the disorder prevalences and familial correlations did not affect the validity of their model-fitting approach, but affected the power to discriminate the correct model. As suggested by Neale and Kendler, the model-fitting approach can be applied to both unselected and selected data and to both twin and family data.

Comorbidity↗

PubMed2003

A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence.

This study describes results from a genome-wide search for quantitative trait loci (QTL) influencing substance dependence vulnerability in adolescence. We utilized regression-based multipoint (and single-point) QTL mapping procedures designed for selected sibpair samples. Selected sibling pairs included 250 proband-sibling pairs from 192 families. Clinical probands (13-19 years of age) were drawn from consecutive admissions to substance abuse treatment facilities in the Denver metropolitan area; siblings of probands ranged in age from 12 to 25 years. In addition to the selected sample, a community-based sample of 3676 adolescents and young adults were utilized to define a clinically-significant, heritable, age- and sex-normed index of substance dependence vulnerability-a priori and independent of our linkage results. Siblings and their parents were genotyped for 374 STR micro-satellite markers distributed across the 22 autosomes (average inter-marker distance=9.2 cM). Non-parametric single-point linkage results indicated 17 markers on 11 chromosomes with nominally significant tests of linkage; six markers with LOD scores greater than 1.0 and one marker (D3S1614) with a LOD score of 2.2. Multipoint mapping corroborated two locations and provided preliminary evidence for linkage to regions on chromosome 3q24-25 (near markers D3S1279 and D3S1614) and chromosome 9q34 (near markers D9S1826 and D9S1838).

Adolescent↗