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1.
J Stud Alcohol Drugs ; 80(5): 557-562, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31603758

RESUMO

OBJECTIVE: The current study used a sample of high-risk adolescents to examine cannabis withdrawal correlates, including assessments of other drug withdrawal and affective lability that may confound cannabis withdrawal measurement. METHOD: A total of 448 high-risk adolescents, living in the Southwest United States, were recruited from a juvenile detention center for a sexual risk-reduction intervention study (60% male; 67% Hispanic). Assessments were administered every 3 months for a year, resulting in five assessments of drug use and withdrawal (cannabis, alcohol, nicotine). Affective lability was also assessed. RESULTS: Forty-two percent of participants endorsed cannabis withdrawal at baseline. Participants used cannabis, on average, 3.3 days/week at baseline and 0.8-1.1 days/week at follow-ups. Cannabis use and withdrawal were only weakly to moderately correlated (r = .14-.32). Unexpectedly, alcohol withdrawal demonstrated strong correlations with cannabis withdrawal at all assessments (r = .41-.55). Furthermore, affective lability measures were related to cannabis withdrawal (r = .22-.32) but not with cannabis use (r = -.03-.09). CONCLUSIONS: Whereas cannabis withdrawal was only weakly to moderately related to cannabis use, it demonstrated strong associations with alcohol withdrawal across all assessments. In addition, affective lability measures were moderately correlated with cannabis withdrawal but not with cannabis use. Thus, other drug withdrawal and individual differences are essential to consider when assessing cannabis withdrawal.

2.
Surg Endosc ; 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945059

RESUMO

BACKGROUND: Overprescribing of opioid medications for patients to be used at home after surgery is common. We sought to ascertain important patient and procedural characteristics that are associated with low versus high rates of self-reported utilization of opioids at home, 1-4 weeks after discharge following gastrointestinal surgery. METHODS: We developed a survey consisting of questions from NIH PROMIS tools for pain intensity/interference and queries on postoperative analgesic use. Adult patients completed the survey weekly during the first month after discharge. Using regression procedures we determined the patient and procedure characteristics that predicted high post-discharge opioid use operationalized as 75 mg oral morphine equivalents/50 mg oxycodone reported taken. RESULTS: The survey response rate was 86% (201/233). High opioid use was reported by 52.7% of patients (106/201). Median reported intake of opioid pain pills was 7 for week #1 and 0 for weeks #2-4. Combinations of acetaminophen and non-steroidal and anti-inflammatory drugs were used by 8.9%-12.5% of patients after discharge. Following adjustment for significant variables of the univariate analysis, last 24-h in-hospital opioid intake remained as a significant co-variate for post-discharge opioid intake. CONCLUSIONS: After gastrointestinal surgery, the equivalent of each oxycodone 5 mg tablet taken in the last 24 h before discharge increases the likelihood of taking the equivalent of > 10 oxycodone 5 mg tablets by 5%. Non-opioid analgesia was utilized in less than half of the cases. Maximizing non-opioid analgesic therapy and basing opioid prescriptions on 24-h pre-discharge opioid intake may improve the quality of post-discharge pain management.

3.
J Pediatr Gastroenterol Nutr ; 68(3): 348-352, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30801394

RESUMO

OBJECTIVES: The aim of the study was to describe use of oral or sublingual cannabis oil (CO) by adolescent and young adult patients with inflammatory bowel disease (IBD). METHODS: A descriptive study of IBD patients 13 to 23 years of age seen between January 2015 through December 2017 at Children's Hospital Colorado. Information obtained included chart abstraction, electronic and interview self-report, and serum cannabinoid levels. We compared CO users and cannabis non-users for clinical characteristics and perceptions of risk. Users of CO provided information on routes, patterns, motivations, and perceived benefits and problems with use. RESULTS: The 15 users and 67 non-users were similar for clinical characteristics and pain and appetite scores. 9 of 15 (60%) CO users had used in the past 30 days, an average of 22 ±â€Š9 times; and 4 used daily. A variety of strengths and CBD:THC ratios were reported. Most common perceived effect of use was on sleep quality, nausea, and increase in appetite. Of the 15 users, 6 used only CO and no additional forms of cannabis. Of these 6 CO only users, 5 reported a medical reason for use, most commonly to relieve pain. CONCLUSIONS: Adolescent and young adults with IBD used oral CO and many used other cannabis products as well. Users perceived some medical benefit. Care teams should strive for open communication about use until further information on safety and efficacy becomes available.

4.
PLoS One ; 13(11): e0206442, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30383806

RESUMO

Externalizing problems (EP), including rule-breaking, aggression, and criminal involvement, are highly prevalent during adolescence, but the adult outcomes of adolescents exhibiting EP are characterized by heterogeneity. Although many youths' EP subside after adolescence, others' persists into adulthood. Characterizing the development of severe EP is essential to prevention and intervention efforts. Multiple predictors of adult antisocial personality disorder (ASPD) and legal outcomes of a large sample (N = 1205) of clinically- or legally-ascertained adolescents (ages 12-19 years) with severe EP were examined. Many psychosocial predictors hypothesized to predict persistence of EP demonstrated zero-order associations with adult outcomes, but accounted for little unique variation after accounting for baseline conduct disorder symptoms (CD) and demographic factors. Baseline measures of intelligence, which explained independent variation in legal outcomes, provided the only consistent exception to this pattern, though future work is needed to parse these effects from those of socioeconomic factors. CD severity during adolescence is a parsimonious index of liability for persistence of EP into adulthood that explains outcome variance above and beyond all other demographic and psychosocial predictors in this sample.

5.
J Addict Med ; 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30475257

RESUMO

OBJECTIVES: Liberalization of marijuana laws in Colorado contributed to increases in cannabis-related adverse events over time. We examined characteristics of patients with healthcare encounters possibly related to cannabis and assessed the temporal association between legalization of recreational marijuana and healthcare encounters possibly attributed to cannabis. METHODS: Annual encounter rates possibly related to cannabis and alcohol were compared using negative binomial regression. Two-time intervals, pre/post-recreational marijuana legalization (January 2009 to December 2013 and January 2014 to December 2015, respectively) were used to examine changes in monthly rates of emergency encounters and hospitalizations possibly related to cannabis. Level and trend changes on encounter rates by legalization period were assessed using interrupted time series analyses. Encounters possibly related to alcohol were used as a comparator group. RESULTS: Most encounters identified during the study period had alcohol-related International Classification of Diseases Diagnosis and Procedural Codes (ICD-9/10-CM) codes (94.8% vs 5.2% for cannabis). Patients with encounters possibly related to cannabis were younger, more likely to be hospitalized and more likely to be admitted to the psychiatric unit than patients with encounters possibly related to alcohol. Initial and sustained effects of encounter rates possibly related to cannabis demonstrated an increased trend in slope before and after recreational marijuana legalization. The slope became more abrupt following legalization with a significant increase in trend during the post-legalization period (ß = 2.7, standard error = 0.3, ρ < 0.0001). No significant change was noted for encounters possibly related to alcohol. CONCLUSIONS: Additional research should identify patients at highest risk of an adverse health event related to cannabis and quantify costs associated with cannabis-related healthcare delivery.

6.
J Am Board Fam Med ; 31(6): 941-943, 2018 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30413550

RESUMO

PURPOSE: The opioid epidemic in the United States is an ongoing public health concern. Health care institutions use standardized patient satisfaction surveys to assess the patient experience and some offer incentives to their providers based on the results. We hypothesized that providers who report being incentivized based on patient satisfaction surveys are more likely to report an impact of such surveys on their opioid prescribing practices. METHODS: We developed a 23-item survey instrument to assess the self-perceived impact of patient satisfaction surveys on opioid prescribing practices in primary care and the potential impact of institutional incentives. The survey was emailed to all 1404 members of the Colorado Academy of Family Physicians. RESULTS: The response rate to the online survey was 10.4% (n = 146). Clinical indications for which responders prescribe opioids included acute pain (93%), cancer pain (85%), and chronic nonmalignant pain (72%). Among physicians using patient satisfaction surveys, incentivized physicians reported at least a slight impact on opioid prescribing 3 times more often than physicians who were not incentivized (36% vs 12%, P = .004). CONCLUSIONS: Efforts to improve patient satisfaction may have potentially untoward effects on providers' opioid prescribing behaviors. Our results suggest a need to further study the impact of provider incentive plans that are based on patient satisfaction scores.

7.
Addiction ; 113(11): 2107-2115, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30091161

RESUMO

BACKGROUND AND AIMS: Adolescents with conduct and substance use problems are at increased risk for premature mortality, but the extent to which these risk factors reflect family- or individual-level differences and account for shared or unique variance is unknown. This study examined common and independent contributions to mortality hazard in adolescents ascertained for conduct disorder (CD) and substance use disorder (SUD), their siblings and community controls, hypothesizing that individual differences in CD and SUD severity would explain unique variation in mortality risk beyond that due to clinical/control status and demographic factors. DESIGN: Mortality analysis in a prospective study (Genetics of Antisocial Drug Dependence Study) that began in 1993. SETTING: Multi-site sample recruited in San Diego, California and Denver, Colorado, USA. PARTICIPANTS: A total of 1463 clinical probands were recruited through the juvenile correctional system, court-mandated substance abuse treatment programs and correctional schools, along with 1399 of their siblings, and 904 controls. MEASUREMENTS: Mortality and cause-of-death were assessed via National Death Index search (released October, 2017). FINDINGS: There were 104 deaths documented among 3766 (1168 female) adolescents and young adults (average age 16.79 years at assessment, 32.69 years at death/censoring). Mortality hazard for clinical probands and their siblings was 4.99 times greater than that of controls (95% confidence interval = 2.40-10.40; P < 0.001). After accounting for demographic characteristics, site, clinical status, familial dependence and shared contributions of CD and SUD, CD independently predicted mortality hazard, whereas SUD severity did not. CONCLUSIONS: In the United States, youth with conduct and substance use disorders and their siblings face far greater risk of premature death than demographically similar community controls. In contrast to substance use disorder severity, conduct disorder is a robust predictor of unique variance in all-cause mortality hazard beyond other risk factors.

8.
Addiction ; 113(11): 2073-2086, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30003630

RESUMO

BACKGROUND AND AIMS: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. METHODS: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. RESULTS: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2  > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. CONCLUSION: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

9.
Am J Addict ; 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29873863

RESUMO

BACKGROUND AND OBJECTIVES: The acquired preparedness model (APM) integrates personality trait research and psychosocial learning, which are theorized to ultimately increase risk for problematic substance use outcomes. METHODS: The present study uses the APM to examine the potential mediational role of positive and negative expectancies on the relationship between impulsivity and two marijuana outcomes (ie, frequency of use and marijuana use disorder [MUD] symptom count) among an at-risk sample of young adults with history of antisocial behavior and substance use in adolescence and their siblings (n = 312). RESULTS: Results suggest a significant indirect effect of sensation seeking on recent marijuana use through positive marijuana expectancies. There also was a significant indirect effect of sensation seeking on past-year MUD symptoms through positive expectancies. No significant indirect effects through negative expectancies were found for either outcome. DISCUSSION AND CONCLUSIONS: Our findings are consistent with the APM and suggest that higher sensation seeking is related to increased positive beliefs about marijuana outcomes, which is related to higher marijuana use and more MUD symptoms. SCIENTIFIC SIGNIFICANCE: These findings suggest that positive expectancies are an important risk factor for marijuana use and misuse, particularly for at-risk individuals with elevated rates of sensation seeking. Positive marijuana expectancies may be important to address in interventions for at-risk individuals. (Am J Addict 2018;XX:1-6).

10.
J Pediatr ; 199: 99-105, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29673723

RESUMO

OBJECTIVE: To evaluate marijuana use by adolescents and young adults with inflammatory bowel disease (IBD). STUDY DESIGN: This descriptive cross-sectional study of patients seen between December 2015 through June 2017 at Children's Hospital Colorado for IBD enrolled patients 13-23 years of age, independent of marijuana use status. Information obtained consisted of chart review, electronic and interview self-report, and serum cannabinoid levels. Marijuana ever-users were compared with never-users for clinical characteristics and perceptions of risk with use; users provided information on routes, patterns, motivations, and perceived benefits and problems with use. RESULTS: Of 99 participants, ever-use was endorsed by 32% (32 of 99) and daily or almost daily use by 9% (9 of 99). Older age was the only characteristic related to endorsing marijuana use. Twenty-nine ever-users completed all questionnaires. After adjusting for age, users were 10.7 times more likely to perceive low risk of harm with regular use (P < .001). At least 1 medical reason for use was endorsed by 57% (17 of 30), most commonly for relief of physical pain (53%, 16 of 30) (2 did not complete all questionnaires). Problems from use were identified by 37% (11 of 30), most commonly craving/strong urge to use. Most common route of use was smoking (83%) followed by edibles (50%), dabbing (40%), and vaping (30%). CONCLUSIONS: Marijuana use by adolescents and young adults with IBD is common and perceived as beneficial. Guidelines for screening, testing, and counseling of marijuana use should be developed for patients with IBD.

11.
Drug Alcohol Depend ; 187: 61-65, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29627407

RESUMO

BACKGROUND: Knowledge of incidence and risk factors for long-term opioid prescribing is critical for surgical patients. In this retrospective cohort study, we linked information available at the time of surgery with prescription data to ascertain characteristics associated with prolonged opioid therapy. METHODS: Patients (n = 6003) with claims in the Colorado All Payer Claims Database (APCD) were matched with 20,501 encounters in a clinical database. Rates of prescription filling were defined by at least one monthly opioid claim relative to the date of surgery. Associations of variables with claims during months 2-6 post-operatively ("long-term prescription filling") were evaluated, and significant variables were jointly modeled using binomial regression. RESULTS: Rates of patients filling opioid prescriptions preoperatively [month (M) relative to date of surgery] were 22%(-3 M), 24%(-2 M), and 27%(-1 M); after surgery, opioid fill rates were 62%(1 M), 28%(2 M), 24%(3), 24%(4 M), 23%(5 M), and 22%(6 M). The majority, 71-76%, of patients filling prescriptions in months 2-6 after surgery had also filled before surgery. In the binomial regression model, long-term opioid use was associated with prior opioid use (p < 0.0001), age ≥26 to <65 relative to age ≥ 65 (p < 0.0001), orthopedic surgery (p = 0.001), colorectal surgery (p = 0.003), multiple procedures (p < 0.0001), and worse physical status classification (p < 0.0001). CONCLUSIONS: Patients who had filled opioid prescriptions preoperatively comprised the majority of the group who filled long-term prescriptions. Surgical procedures were associated with discontinuation of previous opioid prescribing in some patients. For others, surgery marked the initiation of prolonged opioid therapy. Surgical encounters should include interventions aimed to reduce long-term opioid use.


Assuntos
Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Fatores de Tempo , Adulto , Idoso , Colorado , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco
12.
Drug Alcohol Depend ; 183: 25-33, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29223914

RESUMO

OBJECTIVE: To examine if a substance use disorder (SUD), especially cannabis use disorder in adolescence, predicts future medical cannabis card status among high-risk youth. METHODS: Data collection occurred in Denver and San Diego. We recruited adolescents, with or at high risk for SUD and conduct problems (hereafter probands) and their siblings (n=654). Baseline (Wave 1) assessments took place between 1999 and 2008, and follow-up (Wave 2) took place between 2010 and 2013. In initial bivariate analyses, we examined whether baseline DSM-IV cannabis abuse/dependence (along with other potential predictors) was associated with possessing a medical cannabis card in young adulthood (Wave 2). Significant predictors were then included in a multiple binomial regression. Self-reported general physical health was also evaluated at both time points. Finally, within Wave 2, we tested whether card status was associated with concurrent substance dependence. RESULTS: About 16% of the sample self-reported having a medical cannabis card at follow-up. Though bivariate analyses demonstrated that multiple predictors were significantly associated with Wave 2 card status, in our multiple binomial regression only cannabis abuse/dependence and male sex remained significant. At Wave 2, those with a medical cannabis card were significantly more likely to endorse criteria for concurrent cannabis dependence. There was no significant difference in self-reported general physical health. CONCLUSIONS: Cannabis abuse/dependence and male sex positively predicted future medical cannabis card holder status among a sample of high risk adolescents. Physicians conducting evaluations for medical cannabis cards should carefully evaluate and consider past and concurrent cannabis addiction.


Assuntos
Comportamento do Adolescente/psicologia , Abuso de Maconha/epidemiologia , Maconha Medicinal , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , California/epidemiologia , Colorado/epidemiologia , Feminino , Humanos , Masculino , Fatores Sexuais
13.
Arch Sex Behav ; 47(2): 529-536, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28884246

RESUMO

Impulsivity is a personality-based risk factor that has been well studied in relation to risky sexual behavior. Recent conceptualizations of impulsivity have proposed multidimensional facets comprised of premeditation, perseverance, sensation seeking, negative urgency, and positive urgency (UPPS-P model). Prior studies have found that these facets are associated with risky sexual behavior in adolescent and college student samples, but no prior studies have evaluated them in clinical samples. The current study examined how impulsivity-related traits related to two different risky sexual behaviors in a clinical sample of at-risk young adults who had both conduct disorder and substance use disorder symptoms as adolescents (n = 529). Lack of premeditation was also tested as a moderator of the relationship between facets of impulsivity and both risky sex outcomes. Results demonstrated that sensation seeking, negative urgency, and positive urgency were correlated with risky sex behaviors. Additionally, multiple regression analyses indicated that sensation seeking was uniquely associated with the number of sexual partners in the past 5 years, whereas positive urgency was uniquely associated with unprotected sex while under the influence. Finally, a significant interaction between lack of premeditation and negative urgency suggests that at-risk young adults with both high negative urgency and lack of premeditation were the likeliest to have the most sexual partners in the past 5 years. This study adds to the current understanding of the relationship between reward- and affect-driven facets of impulsivity and risky sexual behaviors and may lend utility to the development of interventions for at-risk populations.

14.
Pers Individ Dif ; 114: 42-47, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29038610

RESUMO

Risky driving behaviors are disproportionately high among young adults and impulsivity is a robust risk factor. Recent conceptualizations have proposed multidimensional facets of impulsivity comprised of negative urgency, premeditation, perseverance, sensation seeking, and positive urgency (UPPS-P model). Prior studies have found these facets are associated with risky driving behaviors in college student samples, but no prior studies have examined these facets in clinical samples. This study examined the unique and interactive effects of UPPS-P impulsivity facets on past-year risky driving behaviors in a sample of high-risk young adults (ages 18-30 years) with a history of substance use and antisocial behavior and their siblings (n=1,100). Multilevel Poisson regressions indicated that sensation seeking and negative urgency were uniquely and positively associated with both frequency of past-year reckless driving and driving under the influence. Moreover, lack of premeditation was uniquely and positively associated with reckless driving, whereas lack of perseverance was uniquely and positively associated with driving under the influence. Furthermore, lack of premeditation moderated and strengthened the positive association between sensation seeking and driving under the influence. These study findings suggest that assessing multiple facets of trait impulsivity could facilitate targeted prevention efforts among young adults with a history of externalizing psychopathology.

15.
Drug Alcohol Depend ; 169: 19-25, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27750183

RESUMO

PURPOSE: To examine the associations between substance use and antisocial behavior trajectories and seven risky behaviors over time. METHOD: Data were collected from a high-risk sample of adolescents followed into young adulthood. Five trajectory classes, identified based on dual development of substance use and antisocial behavior symptoms, were used to predict three risky driving and four risky sexual behaviors. RESULTS: In this high-risk sample (n=530), participants reported notably high overall rates of reckless driving (55.5%) and unprotected sex under the influence (44.8%) in the past year. Risky behaviors that are typically of low base rates in population-based studies were also elevated, with 8.8% reporting past-year driving under the influence (DUI) charge, 17.6% reporting lifetime sexually transmitted infection (STI), and 10.4% reporting lifetime injection drug use. The Dual Chronic class had the highest levels of all seven risky behaviors, and were 3-4 times more likely to report risky driving, lifetime STI, and injection drug use than the Relatively Resolved class. Rates of past-year reckless driving and DUI were elevated among classes with persistent antisocial behavior, whereas rates of DUI, DUI charge, and unprotected sex under the influence were elevated among classes with persistent substance use. CONCLUSIONS: Young adults with persistent co-occurring substance use and antisocial behavior engage in multiple very costly risky behaviors. Differential associations between risky behaviors and trajectory classes highlight the need for targeted interventions.


Assuntos
Transtorno da Personalidade Antissocial/complicações , Condução de Veículo/psicologia , Assunção de Riscos , Comportamento Sexual/psicologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Transtorno da Personalidade Antissocial/psicologia , Feminino , Humanos , Masculino , Modelos Psicológicos , Doenças Sexualmente Transmissíveis , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Sexo sem Proteção/psicologia , Adulto Jovem
16.
Alcohol ; 55: 43-50, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27788777

RESUMO

Recent work using a mouse model has identified the glutamate metabotropic receptor 7 (Grm7) gene as a strong candidate gene for alcohol consumption. Although there has been some work examining the effect of human glutamate metabotropic receptor 7 (GRM7) polymorphisms on human substance use disorders, the majority of the work has focused on other psychiatric disorders such as ADHD, major depressive disorder, schizophrenia, bipolar disorder, panic disorder, and autism spectrum disorders. The current study aimed to evaluate evidence for association between GRM7 and alcohol behaviors in humans using a single nucleotide polymorphism (SNP) approach, as well as a gene-based approach. Using 1803 non-Hispanic European Americans (EAs) (source: the Colorado Center on Antisocial Drug Dependence [CADD]) and 1049 EA subjects from an independent replication sample (source: the Genetics of Antisocial Drug Dependence [GADD]), two SNPs in GRM7 were examined for possible association with alcohol consumption using two family-based association tests implemented in FBAT and QTDT. Rs3749380 was suggestively associated with alcohol consumption in the CADD sample (p = 0.010) with the minor T allele conferring risk. There was no evidence for association in the GADD sample. A gene-based test using four Genome-Wide Association Studies (GWAS) revealed no association between variation in GRM7 and alcohol consumption. This study had several limitations: the SNPs chosen likely do not tag expression quantitative trait loci; a human alcohol consumption phenotype was used, complicating the interpretation with respect to rodent studies that found evidence for a cis-regulatory link between alcohol preference and Grm7; and only common SNPs imputed in all four datasets were included in the gene-based test. These limitations highlight the fact that rare variants, some potentially important common signals in the gene, and regions farther upstream were not examined.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Testes Genéticos/métodos , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Receptores de Glutamato Metabotrópico/genética , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Behav Genet ; 46(5): 693-704, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27085880

RESUMO

Common SNPs in nicotinic acetylcholine receptor genes (CHRN genes) have been associated with drug behaviors and personality traits, but the influence of rare genetic variants is not well characterized. The goal of this project was to identify novel rare variants in CHRN genes in the Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) samples and to determine if low frequency variants are associated with antisocial drug dependence. Two samples of 114 and 200 individuals were selected using a case/control design including the tails of the phenotypic distribution of antisocial drug dependence. The capture, sequencing, and analysis of all variants in 16 CHRN genes (CHRNA1-7, 9, 10, CHRNB1-4, CHRND, CHRNG, CHRNE) were performed independently for each subject in each sample. Sequencing reads were aligned to the human reference sequence using BWA prior to variant calling with the Genome Analysis ToolKit (GATK). Low frequency variants (minor allele frequency < 0.05) were analyzed using SKAT-O and C-alpha to examine the distribution of rare variants among cases and controls. In our larger sample, the region containing the CHRNA6/CHRNB3 gene cluster was significantly associated with disease status using both SKAT-O and C-alpha (unadjusted p values <0.05). More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls. These data support a role for genetic variants in CHRN genes and antisocial drug behaviors.


Assuntos
Frequência do Gene/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Receptores Nicotínicos/genética , Adolescente , Transtorno da Personalidade Antissocial , Feminino , Humanos , Masculino , Controle de Qualidade , Software , Adulto Jovem
18.
Psychiatry Res ; 238: 143-149, 2016 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-27086224

RESUMO

Major depressive disorder (MDD) is a prevalent and frequently comorbid psychiatric disorder. This study evaluates the development of depressive symptoms, MDD diagnosis, and suicidal ideation in a high-risk sample (N=524) diagnosed with conduct disorder (CD) and substance use disorder (SUD) symptoms as youth and re-assessed approximately 6.5 years later. Dual trajectory classes of both alcohol and other drug use (AOD) and antisocial behavior (ASB), previously identified using latent class growth analyses (LCGA), were used to predict depression outcomes. The Dual Chronic, Increasing AOD/Persistent ASB, and Decreasing Drugs/Persistent ASB classes had higher past-week depression scores, more past-year MDD symptoms, and were more likely to have past-year MDD than the Resolved class. The Dual Chronic and Decreasing Drugs/Persistent ASB classes also had more past-year MDD symptoms than the Persistent AOD/Adolescent ASB class. Youth at highest risk for developing or maintaining depression in adulthood had the common characteristic of persistent antisocial behavior. This suggests young adulthood depression is associated more with persistent antisocial behavior than with persistent substance use in comorbid youth. As such, interventions targeting high-risk youth, particularly those with persistent antisocial behavior, are needed to help reduce the risk of severe psychosocial consequences (including risk for suicide) in adulthood.


Assuntos
Transtorno da Personalidade Antissocial/psicologia , Transtorno da Conduta/psicologia , Depressão/psicologia , Transtorno Depressivo Maior/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Comportamento do Adolescente , Adulto , Comorbidade , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Ideação Suicida , Suicídio/psicologia , Estados Unidos , Adulto Jovem
19.
PLoS One ; 11(3): e0148373, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26938215

RESUMO

BACKGROUND: The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive. METHODS: We examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995. RESULTS: Linear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment. DISCUSSION: Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed.


Assuntos
Depressão/genética , Predisposição Genética para Doença , Acontecimentos que Mudam a Vida , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Estresse Psicológico/genética , Adolescente , Adulto , Alelos , Maus-Tratos Infantis/reabilitação , Depressão/etiologia , Depressão/fisiopatologia , Feminino , Expressão Gênica , Genótipo , Heterozigoto , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Fatores de Risco , Fatores Sexuais , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Ideação Suicida , Estados Unidos
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