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Thomas J Crowley

Publications and source records attributed to Thomas J Crowley.

At least 19 recordsLinked to original sources
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

Case-control and within-family tests for an association between conduct disorder and 5HTTLPR.

Several lines of research have suggested that serotonin dysfunction is associated with aggression, impulsivity, and antisocial behavior. A functional polymorphism in the promoter region (s, short and l, long allele variant) of the serotonin transporter gene (SLC6A4) that results in decreased transcription of the serotonin transporter gene has been linked with such serotonin dysfunction. To test for an association between 5HTTLPR genotype and conduct disorder diagnosis/aggression. Analysis for association between 5HTTLPR and conduct disorder/aggression using a case-control design and the transmission disequilibrium test. Conduct-disordered adolescents, who were drawn from admissions to a program that treats adolescents with serious substance and behavior problems, and conduct-disordered siblings of these patients (n, 297) were compared with non-conduct-disordered control adolescents and non-conduct-disordered siblings of these controls (n, 93). Second, using patient families where parental DNA was available, transmission disequilibrium tests were conducted for two phenotypes: (1) conduct disorder (74 trios), and (2) conduct disorder with at least one aggressive symptom (57 trios). Case-control analyses suggested a strong association between the ss genotype and conduct disorder (chi2(2) = 14.3; P < 0.01). Within-family analyses for conduct disorder with at least one aggressive symptom significantly favored greater transmission of the s-allele to affected offspring (chi(tdt)(2) = 4.13; P = 0.04); for conduct disorder, without aggressive symptoms, however, results were non-significant (chi(tdt)(2) = 1.61; P = 0.20). These data suggest that the s-allele may confer some risk for aggressive behavior or may be in linkage disequilibrium with such an allele.

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

Climate sensitivity constrained by temperature reconstructions over the past seven centuries.

The magnitude and impact of future global warming depends on the sensitivity of the climate system to changes in greenhouse gas concentrations. The commonly accepted range for the equilibrium global mean temperature change in response to a doubling of the atmospheric carbon dioxide concentration, termed climate sensitivity, is 1.5-4.5 K (ref. 2). A number of observational studies, however, find a substantial probability of significantly higher sensitivities, yielding upper limits on climate sensitivity of 7.7 K to above 9 K (refs 3-8). Here we demonstrate that such observational estimates of climate sensitivity can be tightened if reconstructions of Northern Hemisphere temperature over the past several centuries are considered. We use large-ensemble energy balance modelling and simulate the temperature response to past solar, volcanic and greenhouse gas forcing to determine which climate sensitivities yield simulations that are in agreement with proxy reconstructions. After accounting for the uncertainty in reconstructions and estimates of past external forcing, we find an independent estimate of climate sensitivity that is very similar to those from instrumental data. If the latter are combined with the result from all proxy reconstructions, then the 5-95 per cent range shrinks to 1.5-6.2 K, thus substantially reducing the probability of very high climate sensitivity.

Journal Article↗
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

Adolescent inhalant use among male patients in treatment for substance and behavior problems: two-year outcome.

UNLABELLED: Adolescent inhalant users are significantly more likely than other patients to have conduct disorder, to report abuse and neglect, and to have previously attempted suicide. Yet little has been published regarding treatment outcome for inhalant users. METHODS: Eighty male adolescents admitted to a residential treatment program underwent baseline assessment during treatment, and follow-up assessment at two-years post admission. Subjects reporting any lifetime inhalant use at baseline (n = 34) were compared to the other patients (n = 46) on 4 outcome variables. RESULTS: Adolescents reporting any lifetime inhalant use at baseline assessment reported twice as many past-year conduct disorder symptoms at two-year follow up (p = 0.03). The relationship between inhalant use and conduct disorder symptoms remained significant (p = 0.03) in analyses that controlled for age, time in jail or restricted environments in the 6-months preceding follow-up, as well as baseline-reported lifetime number of conduct disorder symptoms. Inhalant users were not significantly worse on these other outcome measures: crime in the last month (p = 0.60), days of nontobacco substance use in the last 6 months (p = 0.65), or, commission of selected crimes in the last 6 months (p = 0.06). CONCLUSIONS: Inhalant use among adolescent males in treatment for substance and behavior problems may predict more severe conduct disorder symptoms after treatment.

Administration, Inhalation↗
PubMed2006

A risk-taking "set" in a novel task among adolescents with serious conduct and substance problems.

OBJECTIVE: Adolescent patients' conduct disorder and substance use disorder symptoms are "risky behaviors" with unpredictable rewards and punishments. The authors asked whether such youths also take excessive risks in new situations without prior learning, peer pressure, or intoxication. METHOD: Subjects were 20 adolescent patients in a program treating conduct disorder and substance use disorder and 20 controls. All were substance free > or =7 days; underwent substance-related, psychological, and social assessments; and performed the Balloon Analogue Risk Task: mouse presses inflated a computerized "balloon" image, each press earning 1 cent. The 30 balloons "popped" at unpredictable sizes; earnings from popped balloons were lost. A "Collect" response saved current earnings and advanced to the next balloon. RESULTS: Mean number of inflating presses: patients, 1021 and controls, 705 (p = .001); group differences were stable from the task's beginning. Mean inflating presses before a "collect" response: patients, 38.6 and controls, 24.0 (p = .0005). Mean balloons popped: patients, 9.8 and controls, 6.3 (p = .001). Patients (versus controls) reported more aggressiveness and substance use and perceived less risk from substances. Patients' responses were significantly slower than those of controls. CONCLUSIONS: From the beginning of this novel task, conduct disorder and substance use disorder patients (compared with controls) took more risks, indicating an initial risk-taking propensity, although patients' slower responses argued against "impulsive, thoughtless" behavior.

Adolescent↗
PubMed2006

Adolescents and substance-related disorders: research agenda to guide decisions on Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V).

AIMS: Since the publication of the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), many studies have addressed substance use disorders (SUD) in adolescents. Based on that adolescent literature, this paper suggests further research to help guide decisions about revising for DSM-V the SUD criteria in DSM-IV. METHODS: The author has reviewed the 'Substance Related Disorders' section of DSM-IV-TR, recalled his experience in helping to draft that section, accessed relevant articles in PubMed and reviewed his own extensive file of literature citations. RESULTS: This paper suggests six questions for adolescent research to help guide the framers of DSM-V's 'Substance Related Disorders' section: (a) DSM-IV did not provide a diagnosis of cannabis withdrawal; should DSM-V continue that position? (b) Should SUD be included or referenced among 'Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence'? (c) Can inter-rater reliability of the substance abuse (SA) criteria be improved with altered example situations, text descriptions or phrasing of the current criteria? (d) Between ages 14 and 18 years is earlier onset of SUD a severity marker that could be incorporated into DSM-V as a predictor of worse course? (e) In DSM-V could a phenotypic descriptor of pathological multi-substance involvement document severity and predict course of SUD? (f) Could clinicians and patients benefit from DSM-V-related postpublication procedures for classifying emerging new drugs into DSM-V's categories? CONCLUSIONS: Without substantive changes in SA or substance dependence diagnostic criteria, research may improve the usefulness of those criteria for adolescents.

Adolescent↗
PubMed2006

Validity of transdermal alcohol monitoring: fixed and self-regulated dosing.

BACKGROUND: To study the validity of transdermal assessment of alcohol concentration measured by a lightweight, noninvasive device. METHODS: Subjects wore a 227-g anklet that sensed transdermal alcohol concentrations (TACs) every 15 to 30 minutes, downloading results to a remote computer each day. Twenty-four subjects entered a laboratory and received a dose of 0, 0.28, or 0.56 g/kg of ethanol. Breath alcohol concentrations (BrAC) and TAC were measured every 15 to 30 minutes Twenty others [10 alcohol dependent (AD) and 10 not (NAD)] in the community who wore the anklet for 8 days kept a drinking log and provided a BrAC sample each day. RESULTS: In the laboratory, no zero-dose subject, and every subject receiving alcohol, had alcohol-positive TACs. The device distinguished low- and high-alcohol-dosing groups using peak (t14 = 3.37; p < 0.01) and area under the curve (t14 = 3.42; p < 0.01) of TACs. Within dosing groups, average TAC curves were broader (right-shifted) and had lower peaks than average BrAC curves. For community participants, self-reported number of drinks (t18 = -3.77; p < 0.01), area under the TAC curve (t9.5 = -3.56; p < 0.01), and mean TAC (t9.9 = -3.35; p < 0.01) all significantly distinguished the AD and NAD groups. However, individual transdermal readings were not reliably quantitatively equivalent to simultaneously obtained breath results. CONCLUSIONS: Within the limits of the laboratory study, the device consistently detected consumption of approximately 2 standard drinks. On average, the device shows discriminative validity as a semiquantitative measure of alcohol consumption but individual readings often are not equivalent to simultaneous BrACs.

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

Measuring impulsivity in adolescents with serious substance and conduct problems.

Adolescents with substance use and conduct disorders have high rates of aggression and attention deficit hyperactivity disorder (ADHD), all of which have been characterized in part by impulsivity. Developing measures that capture impulsivity behaviorally and correlate with self-reported impulsivity has been difficult. One promising behavioral measure, however, is a variant of the continuous performance test, the Immediate Memory Test/Delayed Memory Test (IMT/DMT). The authors showed significant group differences between adolescents in treatment for serious substance and conduct problems and community controls on impulsivity measures, both behavioral and self-report, as well as on aggression and problem behavior measures. Furthermore, the IMT/DMT correlated significantly with self-reported impulsivity. In summary, the IMT/DMT may be an effective behavioral measure of impulsivity in adolescents.

Adolescent↗
PubMed2006

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↗
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↗
PubMed2004

Inhalant use, abuse, and dependence among adolescent patients: commonly comorbid problems.

OBJECTIVE: Little is known about adolescents with DSM-IV-defined inhalant abuse and dependence. The aim of this study was to compare comorbidity among (1) adolescents with inhalant use disorders, (2) adolescents who reported using inhalants without inhalant use disorder, and (3) other adolescent patients drawn from an adolescent drug and alcohol treatment program. METHOD: The authors examined 847 admissions of patients who had completed structured diagnostic assessments. The three groups were compared for noninhalant substance use disorders, posttraumatic stress disorder, conduct disorder, major depression, previous suicide attempts, and physical/sexual abuse and neglect. RESULTS: Adolescents with inhalant abuse or dependence (group 1; n = 28) were significantly more likely to meet lifetime criteria for abuse or dependence on alcohol, hallucinogens, nicotine, cocaine, and amphetamines, to have had major depression, and to have attempted suicide compared with other adolescent patients who reported never using inhalants (group 3); adolescents with inhalant use disorders also reported significantly more abuse and neglect. Adolescents with inhalant abuse or dependence (group 1) did not differ significantly on any measure compared with adolescents who reported using inhalants without an inhalant use disorder (group 2). CONCLUSIONS: Adolescent patients with a history of inhalant use, abuse, or dependence entering treatment should be carefully screened for noninhalant substance use disorders, major depression, suicidality, and abuse and neglect.

Adolescent↗
PubMed2003

Comparing linear and nonlinear mixed model approaches to cosinor analysis.

The cosinor model, used for variables governed by circadian and other biological rhythms, is a nonlinear model in the amplitude and acrophase parameters that has a linear representation upon transformation. With linear cosinor analysis, amplitude and acrophase for each harmonic can be computed as nonlinear functions of the estimated linear regression coefficients. Here a flexible mixed model approach to cosinor analysis is considered, where the fixed effect parameters may enter nonlinearly as acrophase and amplitude for each harmonic or linearly after transformation to regression coefficients. In addition, the random effects may enter nonlinearly as subject-specific deviations from the acrophases and amplitudes or linearly as subject-specific deviations from the regression coefficients. It is also possible for the fixed effects to enter nonlinearly while the random effects enter linearly. Additionally, we evaluate whether including higher order linear harmonic terms as random effects, that is, Rao-Khatri 'covariance adjustment', improves precision. Applying the delta method to nonlinear functions of the parameters from linear mixed cosinor models to obtain approximate variances produces results that are often identical to results from nonlinear mixed models. Consequently, traditional linear cosinor analysis can often be used to estimate and compare the nonlinear parameters of interest, that is, amplitudes and acrophases, via the delta method. This is advantageous since the nonlinear mixed model may have convergence difficulties for more complex models. However, for some multiple-group analyses, the linear cosinor transformation should not be used and we clarify when the two methods are equivalent and when they differ.

Circadian Rhythm↗
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↗