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1.
Mol Psychiatry ; 22(12): 1767-1775, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28070124

RESUMO

Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (ß: -0.124; P<4.5 × 10-9), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.


Assuntos
Alcoolismo/genética , Alcoolismo/fisiopatologia , Negro ou Afro-Americano/genética , Eletroencefalografia , Endofenótipos , Predisposição Genética para Doença , Adulto , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/fisiopatologia , Alcoolismo/diagnóstico , População Negra/genética , Encéfalo/fisiopatologia , Butirilcolinesterase/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
2.
Psychol Med ; 46(3): 563-73, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26688007

RESUMO

BACKGROUND: Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples. METHOD: We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537). RESULTS: Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples. CONCLUSIONS: A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Abuso Sexual na Infância/psicologia , Delitos Sexuais/psicologia , Adulto , Austrália , Criança , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores Sexuais , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
3.
Psychol Med ; 45(16): 3505-15, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26281760

RESUMO

BACKGROUND: Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. METHOD: Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. RESULTS: Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. CONCLUSIONS: Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.


Assuntos
Transtorno da Conduta/genética , Doenças em Gêmeos/genética , Interação Gene-Ambiente , Transtornos Relacionados ao Uso de Substâncias/genética , Gêmeos/genética , Adolescente , Adulto , Austrália , Cannabis , Criança , Comorbidade , Etanol , Feminino , Humanos , Masculino , Análise Multivariada , Nicotina , Fenótipo , Sistema de Registros , Fatores de Risco , Adulto Jovem
4.
Psychol Med ; 44(1): 143-59, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23551901

RESUMO

BACKGROUND: There is evidence that measures of alcohol consumption, dependence and abuse are valid indicators of qualitatively different subtypes of alcohol involvement yet also fall along a continuum. The present study attempts to resolve the extent to which variations in alcohol involvement reflect a difference in kind versus a difference in degree. METHOD: Data were taken from the 2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions. The sample (51% male; 72% white/non-Hispanic) included respondents reporting past 12-month drinking at both waves (wave 1: n = 33644; wave 2: n = 25186). We compared factor mixture models (FMMs), a hybrid of common factor analysis (FA) and latent class analysis (LCA), against FA and LCA models using past 12-month alcohol use disorder (AUD) criteria and five indicators of alcohol consumption reflecting frequency and heaviness of drinking. RESULTS: Model comparison revealed that the best-fitting model at wave 1 was a one-factor four-class FMM, with classes primarily varying across dependence and consumption indices. The model was replicated using wave 2 data, and validated against AUD and dependence diagnoses. Class stability from waves 1 to 2 was moderate, with greatest agreement for the infrequent drinking class. Within-class associations in the underlying latent factor also revealed modest agreement over time. CONCLUSIONS: There is evidence that alcohol involvement can be considered both categorical and continuous, with responses reduced to four patterns that quantitatively vary along a single dimension. Nosologists may consider hybrid approaches involving groups that vary in pattern of consumption and dependence symptomatology as well as variation of severity within group.


Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo/classificação , Síndrome de Abstinência a Substâncias , Adolescente , Adulto , Transtornos Relacionados ao Uso de Álcool/classificação , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Assunção de Riscos , Índice de Gravidade de Doença , Síndrome de Abstinência a Substâncias/etiologia , Adulto Jovem
5.
Psychol Med ; 44(5): 1053-64, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23795654

RESUMO

BACKGROUND: DSM-IV specifies a hierarchal diagnostic structure such that an oppositional defiant disorder (ODD) diagnosis is applied only if criteria are not met for conduct disorder (CD). Genetic studies of ODD and CD support a combination of shared genetic and environmental influences but largely ignore the imposed diagnostic structure. METHOD: We examined whether ODD and CD share an underlying etiology while accounting for DSM-IV diagnostic specifications. Data from 1446 female twin pairs, aged 11-19 years, were fitted to two-stage models adhering to the DSM-IV diagnostic hierarchy. RESULTS: The models suggested that DSM-IV ODD-CD covariation is attributed largely to shared genetic influences. CONCLUSIONS: This is the first study, to our knowledge, to examine genetic and environmental overlap among these disorders while maintaining a DSM-IV hierarchical structure. The findings reflect primarily shared genetic influences and specific (i.e. uncorrelated) shared/familial environmental effects on these DSM-IV-defined behaviors. These results have implications for how best to define CD and ODD for future genetically informed analyses.


Assuntos
Transtornos de Deficit da Atenção e do Comportamento Disruptivo/genética , Transtorno da Conduta/genética , Doenças em Gêmeos/genética , Adolescente , Adulto , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/etiologia , Criança , Transtorno da Conduta/etiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Doenças em Gêmeos/etiologia , Feminino , Humanos , Adulto Jovem
6.
Psychol Med ; 43(4): 813-23, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22804877

RESUMO

BACKGROUND: Initiation of cannabis use typically follows alcohol use, but the reverse order does occur and is more common for African-Americans (AAs) than European-Americans (EAs). The aim of this study was to test for differences in the order of initiation of cannabis and alcohol use between AA and EA women and to determine whether order and ethnicity contribute independently to risk for rapid progression to cannabis-related problems. Method Data were drawn from structured psychiatric interviews of 4102 women (mean age = 21.6 years), 3787 from an all-female twin study and 315 from a high-risk family study; 18.1% self-identified as AA, 81.9% as EA. Ethnicity and order of initiation of cannabis and alcohol use were modeled as predictors of transition time from first use to onset of cannabis use disorder symptom(s) using Cox proportional hazards regression analyses. RESULTS: AA women were nearly three times as likely as EA women to initiate cannabis use before alcohol use. Using cannabis before alcohol [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.08-1.93] and AA ethnicity (HR 1.59, 95% CI 1.13-2.24) were both associated with rapid progression from first use to cannabis symptom onset even after accounting for age at initiation and psychiatric risk factors. CONCLUSIONS: The findings indicate that AA women are at greater risk for rapid development of cannabis-related problems than EA women and that this risk is even higher when cannabis use is initiated before alcohol use. Prevention programs should be tailored to the various patterns of cannabis use and relative contributions of risk factors to the development of cannabis-related problems in different ethnic groups.


Assuntos
Consumo de Bebidas Alcoólicas/etnologia , Alcoolismo/etnologia , Doenças em Gêmeos , Abuso de Maconha/etnologia , Fumar Maconha/etnologia , Adolescente , Adulto , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Idade de Início , Progressão da Doença , Saúde da Família , Feminino , Humanos , Entrevista Psicológica , Masculino , Prevalência , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , População Branca/psicologia , População Branca/estatística & dados numéricos , Adulto Jovem
7.
Mol Psychiatry ; 17(4): 445-50, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21968928

RESUMO

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Adolescente , Adulto , Idoso , Alelos , População Negra/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética
8.
Psychol Med ; 42(11): 2421-31, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22423619

RESUMO

BACKGROUND: Familial influences on remission from alcohol use disorder (AUD) have been studied using family history of AUD rather than family history of remission. The current study used a remission phenotype in a twin sample to examine the relative contributions of genetic and environmental influences to remission. METHOD: The sample comprised 6183 twins with an average age of 30 years from the Australian Twin Registry. Lifetime history of alcohol abuse and dependence symptoms and symptom recency were assessed with a structured telephone interview. AUD was defined broadly and narrowly as history of two or more or three or more abuse or dependence symptoms. Remission was defined as absence of symptoms at time of interview among individuals with lifetime AUD. Standard bivariate genetic analyses were conducted to derive estimates of genetic and environmental influences on AUD and remission. RESULTS: Environmental influences alone accounted for remission in males and for 89% of influences on remission in females, with 11% due to genetic influences shared with AUD, which decreased the likelihood of remission. For women, more than 80% of influences on remission were distinct from influences on AUD, and environmental influences were from individual experiences only. For men, just over 50% of influences on remission were distinct from those on AUD, and the influence of environments shared with the co-twin were substantial. The results for the broad and narrow phenotypes were similar. CONCLUSIONS: The current study establishes young adult remission as a phenotype distinct from AUD and highlights the importance of environmental influences on remission.


Assuntos
Transtornos Relacionados ao Uso de Álcool/epidemiologia , Sistema de Registros , Remissão Espontânea , Adulto , Transtornos Relacionados ao Uso de Álcool/genética , Austrália/epidemiologia , Doenças em Gêmeos/epidemiologia , Feminino , Humanos , Masculino , Fenótipo , Fatores Sexuais , Adulto Jovem
9.
Psychol Med ; 41(7): 1497-505, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21054919

RESUMO

BACKGROUND: The few genetically informative studies to examine post-traumatic stress disorder (PTSD) and alcohol dependence (AD), all of which are based on a male veteran sample, suggest that the co-morbidity between PTSD and AD may be attributable in part to overlapping genetic influences, but this issue has yet to be addressed in females.MethodData were derived from an all-female twin sample (n=3768) ranging in age from 18 to 29 years. A trivariate genetic model that included trauma exposure as a separate phenotype was fitted to estimate genetic and environmental contributions to PTSD and the degree to which they overlap with those that contribute to AD, after accounting for potential confounding effects of heritable influences on trauma exposure. RESULTS: Additive genetic influences (A) accounted for 72% of the variance in PTSD; individual-specific environmental (E) factors accounted for the remainder. An AE model also provided the best fit for AD, for which heritability was estimated to be 71%. The genetic correlation between PTSD and AD was 0.54. CONCLUSIONS: The heritability estimate for PTSD in our sample is higher than estimates reported in earlier studies based almost exclusively on an all-male sample in which combat exposure was the precipitating traumatic event. However, our findings are consistent with the absence of evidence for shared environmental influences on PTSD and, most importantly, the substantial overlap in genetic influences on PTSD and AD reported in these investigations. Additional research addressing potential distinctions by gender in the relative contributions of genetic and environmental influences on PTSD is merited.


Assuntos
Alcoolismo/genética , Alcoolismo/psicologia , Predisposição Genética para Doença/psicologia , Meio Social , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto , Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/estatística & dados numéricos , Estudos de Coortes , Comorbidade , Vítimas de Crime/psicologia , Vítimas de Crime/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Entrevistas como Assunto , Estudos Longitudinais , Missouri , Fatores de Risco , Adulto Jovem
10.
Drug Alcohol Depend ; 162: 162-9, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27012434

RESUMO

INTRODUCTION: To examine the contribution of trauma exposure to cannabis initiation and transition to first cannabis use disorder (CUD) symptom in African-American (AA) and European-American (EA) emerging adults. METHODS: Data are from the Missouri Adolescent Female Twins Study [(N=3787); 14.6% AA; mean age=21.7 (SD 3.8)]. Trauma exposures (e.g. sexual abuse, physical abuse, witnessing another person being killed or injured, experiencing an accident, and experiencing a disaster) were modeled as time-varying predictors of cannabis initiation and transition to CUD symptom using Cox proportional hazards regression. Other substance involvement and psychiatric disorders were considered as time-varying covariates. RESULTS: Analyses revealed different trauma-related and psychiatric predictors for cannabis use supporting racially distinct etiologic models of cannabis involvement. For AA women, history of witnessing injury/death or experiencing a life-threatening accident was associated with cannabis initiation across the complete emerging adult risk period while sexual abuse predicted cannabis initiation only before 15 years old. For EA women, history of sexual or physical abuse and major depressive disorder (MDD) predicted cannabis initiation and physical abuse and MDD predicted transition from initiation to first CUD symptom. No association was discovered between trauma exposures and transition to first CUD symptom in AA women. CONCLUSIONS: Results reveal trauma exposures as important contributors to cannabis initiation and to a lesser extent transition to CUD symptom, with different trauma types conferring risk for cannabis involvement in AA and EA women. Findings suggest the importance of considering racial/ethnic differences when developing etiologic models of cannabis involvement.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Negro ou Afro-Americano/psicologia , Acontecimentos que Mudam a Vida , Abuso de Maconha/diagnóstico , Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Gêmeos/psicologia , População Branca/psicologia , Adolescente , Adulto , Feminino , Humanos , Prognóstico , Estados Unidos , Adulto Jovem
11.
Transl Psychiatry ; 6: e761, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-27003187

RESUMO

Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.


Assuntos
Alcoolismo/genética , Adulto , Idade de Início , Austrália , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Linhagem , Fenótipo , Estados Unidos , População Branca
12.
Arch Gen Psychiatry ; 56(6): 557-63, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10359473

RESUMO

BACKGROUND: Depression affects more women than men and often aggregates in families. Using a community-based sample of twins, we examined the contributions of genetic and environmental factors to the risk of developing major depressive disorder and the effect of sex and different definitions of depression on the relative contributions of genetic and environmental effects. Sex differences in genetic effects were also studied. METHODS: A volunteer sample of Australian twins (2662 pairs) was interviewed using an abbreviated version of the Semi-Structured Assessment for the Genetics of Alcoholism, a semi-structured lay interview designed to assess psychiatric disorders. Depression was defined using 3 different criteria sets: DSM-III-R major depressive disorder, DSM-IV major depressive disorder, and severe DSM-IV major depressive disorder. Genetic and environmental contributions to the liability to develop depression were estimated using genetic model fitting. RESULTS: Lifetime prevalences were 31% in women and 24% in men for DSM-III-R major depressive disorder, 22% in women and 16% in men for DSM-IV major depressive disorder, and 9% in women and 3% in men for severe DSM-IV major depressive disorder. In women, the simplest model to fit the data implicated genetic factors and environmental factors unique to the individual in the development of depression, with heritability estimates ranging from 36% to 44%. In men, depression was only modestly familial, and thus individual environmental factors played a larger role in the development of depression. For DSM-III-R major depressive disorder, there were statistically different estimates for heritability for men vs. women. For both sexes, the relative contributions of genetic and environmental factors were stable using different definitions of depression. CONCLUSIONS: There was moderate familial aggregation of depression in women and this primarily was attributable to genetic factors. In men, there was only modest familial aggregation of depression. For both men and women, individual environmental experiences played a large role in the development of depression. Major depressive disorder as defined by DSM-III-R was more heritable in women as compared with men. The relative contributions of genetic and environmental factors in the development of depression were similar for varying definitions of depression, from a broad definition to a narrow definition.


Assuntos
Transtorno Depressivo/epidemiologia , Doenças em Gêmeos/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/genética , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/genética , Família , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Prevalência , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Meio Social , Terminologia como Assunto , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
13.
Arch Gen Psychiatry ; 56(7): 655-61, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10401514

RESUMO

BACKGROUND: Nicotine and alcohol dependence often occur together. We examined data from male twin pairs to determine whether there are genetic or environmental influences common to nicotine and alcohol dependence, and, if so, to estimate the magnitude and correlation of these influences. METHODS: Subjects were 3356 male-male twin-pair members of the Vietnam Era Twin Registry who participated in a 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised. Genetic model fitting was performed to estimate the magnitude and correlation of genetic and environmental contributions to lifetime nicotine and alcohol dependence. RESULTS: The heritability of nicotine dependence was 60.3% (95% confidence interval [CI], 55.4%-65.2%); that of alcohol dependence, 55.1% (95% CI, 49.7%-60.5%). The best-fitting model for the co-occurrence of lifetime nicotine and alcohol dependence included a substantial genetic correlation between both disorders (r = 0.68; 95% CI, 0.61-0.74) and a modest unique environmental correlation (r = 0.23; 95% CI, 0.14-0.32). CONCLUSIONS: These data suggest a common genetic vulnerability to nicotine and alcohol dependence in men. This common genetic influence may partially explain the clinical and epidemiological observations that alcoholics are often dependent smokers.


Assuntos
Alcoolismo/genética , Tabagismo/genética , Adulto , Alcoolismo/epidemiologia , Comorbidade , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Fatores Sexuais , Tabagismo/epidemiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos
14.
Drug Alcohol Depend ; 153: 250-7, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26036603

RESUMO

INTRODUCTION: Alcohol use disorder symptoms frequently occur in adolescents and younger adults who seldom acknowledge a need for help. We identified sociodemographic, clinical, and familial predictors of alcohol problem recognition and help seeking in an offspring of twin sample. METHOD: We analyzed longitudinal data from the Children of Alcoholics and Twins as Parents studies, which are combinable longitudinal data sources due to their equivalent design. We analyzed respondents (n=1073, 56.0% of the total sample) with alcohol use disorder symptoms at the baseline interview. Familial characteristics included perceptions of alcohol problems and help seeking for alcohol problems within the immediate family and a categorical variable indicating genetic and environmental risk. We used logistic regression to examine predictors of alcohol problem recognition and help seeking. RESULTS: Approximately 25.9% recognized their alcohol problems and 26.7% sought help for drinking. In covariate-adjusted analyses, help seeking among family members predicted problem recognition, several clinical characteristics predicted both problem recognition and help seeking, and familial risk predicted help seeking. Alcohol problem recognition mediated the association between alcohol use disorder symptoms and incident help seeking. CONCLUSIONS: Facilitating the self-recognition of alcohol use disorder symptoms, and perhaps the awareness of family members' help seeking for alcohol problems, may be potentially promising methods to facilitate help seeking.


Assuntos
Transtornos Relacionados ao Uso de Álcool/diagnóstico , Transtornos Relacionados ao Uso de Álcool/psicologia , Autoavaliação Diagnóstica , Família/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Gêmeos/psicologia , Adolescente , Adulto , Feminino , Interação Gene-Ambiente , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Fatores de Risco , Adulto Jovem
15.
Drug Alcohol Depend ; 150: 98-104, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25772435

RESUMO

BACKGROUND: In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology. METHODS: We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI. RESULTS: All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs]=1.28-2.00, p<0.01). Cannabis use and endorsing ≥3 symptoms were associated with unplanned (SANP; ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts (p>0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG=0.45) and environmental (rE=0.21) factors were responsible for the covariance between cannabis involvement and SI. CONCLUSIONS: Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders.


Assuntos
Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Suicídio/psicologia , Adulto , Austrália , Feminino , Humanos , Masculino , Gêmeos/psicologia , Prevenção do Suicídio
16.
Am J Psychiatry ; 146(5): 640-4, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2712169

RESUMO

The authors studied the other recent psychiatric symptoms of 218 subjects who reported having had depressive episodes within the past year to determine the influence of the nondepressive symptoms on whether the subjects discussed the depressive episodes with a doctor. Symptoms of panic and obsessive-compulsive disorders encouraged discussion of a depressive episode, but symptoms of drug abuse/dependence inhibited such discussion. The findings illustrate the bias in studying only patients who seek treatment, point to groups of persons who may need psychiatric help, and provide insight into the complex process of help seeking.


Assuntos
Transtorno Depressivo/psicologia , Transtornos Mentais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Relações Médico-Paciente , Adulto , Transtornos de Ansiedade/psicologia , Feminino , Humanos , Masculino , Pânico , Projetos de Pesquisa/normas , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/psicologia
17.
Am J Psychiatry ; 158(7): 1084-90, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11431230

RESUMO

OBJECTIVE: The prognostic validity of the DSM-IV diagnoses of alcohol abuse and alcohol dependence was evaluated by examining the 5-year clinical course associated with those diagnoses in a large group of predominantly blue-collar men and women. METHOD: Personal semistructured interviews were carried out 5 years after an initial evaluation with 1,346 (75%) of the approximately 1,800 men and women participating in the Collaborative Study on the Genetics of Alcoholism who were eligible for follow-up. RESULTS: About two-thirds of the 298 subjects with DSM-IV alcohol dependence at baseline maintained that diagnosis during the 5-year study period. Fifty-five percent of the 288 subjects with DSM-IV alcohol abuse at baseline continued to meet one or more of the 11 DSM-IV abuse/dependence criteria, and 3.5% went on to meet the criteria for dependence at follow-up. Among the 760 subjects with no alcohol diagnosis at baseline, 2.5% met the criteria for alcohol dependence and 12.8% for alcohol abuse at follow-up. Baseline characteristics that predicted the occurrence of any of the 11 DSM-IV abuse/dependence criteria during the 5-year interval included male gender, lack of marital stability, presence of several of the criteria for dependence, and history of illicit drug use. CONCLUSIONS: The data suggest that over 5 years the DSM-IV diagnosis of alcohol dependence predicts a chronic disorder with a relatively severe course, while DSM-IV alcohol abuse predicts a less persistent, milder disorder that does not usually progress to dependence.


Assuntos
Alcoolismo/diagnóstico , Adulto , Alcoolismo/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Reprodutibilidade dos Testes , Fatores Sexuais , Classe Social , Terminologia como Assunto , Estados Unidos
18.
Am J Psychiatry ; 158(11): 1891-8, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11691697

RESUMO

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a highly heritable but clinically heterogeneous syndrome. The study examined the familiality and heritability of ADHD subtypes as defined by DSM-IV and by latent-class analysis in a population sample of adolescent female twins. METHOD: To determine which elements of ADHD cluster together, latent-class analysis was applied to data obtained from parents on the 18 DSM-IV ADHD symptoms in 4,036 female twins age 13-23 years in a population sample identified from the registry of all births in Missouri for the years 1968-1996. Relative risk and odds ratios were used to assess within-subtype and between-subtype familiality and heritability of both DSM-IV and latent-class ADHD subtypes. RESULTS: Latent-class analysis was most compatible with the existence of three mild and three severe classes of ADHD symptoms in the general population. The three severe classes showed moderate overlap with DSM-IV ADHD subtypes. The primarily inattentive and combined subtypes of DSM-IV ADHD co-clustered within families. The primarily hyperactive/impulsive DSM-IV subtype and the individual latent-class analysis subtypes did not co-cluster. Subtypes defined by both approaches were highly heritable. CONCLUSIONS: Unlike DSM-IV subtypes of ADHD, latent-class ADHD subtypes appear to be independently transmitted in families. These classes may be more appropriate targets for molecular genetic studies of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Gêmeos/genética , Adolescente , Comportamento do Adolescente/psicologia , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Prevalência , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença
19.
Am J Psychiatry ; 153(1): 74-82, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8540597

RESUMO

OBJECTIVE: Many of the studies linking anorexia nervosa and bulimia nervosa to substance use disorders suffer from problems with small samples; some lack rigorous definitions of the syndromes, and it is difficult to determine whether eating problems were primarily temporary consequences of heavy substance use or drugs were temporarily used in an effort to control appetite. The goal of this study was to evaluate the relationship between alcohol dependence and eating disorders. METHOD: Structured interviews were carried out with 2,283 women and 1,982 men as part of the Collaborative Study on the Genetics of Alcoholism. Data on drug abuse and dependence, psychiatric disorders, and symptoms of anorexia and bulimia were evaluated among alcohol-dependent probands, their relatives, comparison probands, and their relatives. RESULTS: Lifetime rates for anorexia and bulimia were 1.41% and 6.17%, respectively, for the alcohol-dependent women, and bulimia was observed in 1.35% of the alcoholic men. However, once the impact of additional primary diagnoses was controlled for, anorexia was seen in only 1.26% of the women with primary alcohol dependence and none of the alcohol-dependent men; the rates for bulimia were 3.46% and 0.72%, respectively. There was no evidence of a strong familial crossover between alcohol dependence and anorexia or bulimia. CONCLUSIONS: While the rate of anorexia was not elevated in alcoholics after controlling for other disorders, bulimia did occur at a greater than expected rate. However, both eating disorders were relatively rare, and much of the association with alcoholism occurred in the context of additional preexisting or secondary psychiatric disorders.


Assuntos
Alcoolismo/epidemiologia , Anorexia Nervosa/epidemiologia , Bulimia/epidemiologia , Família , Adulto , Alcoolismo/genética , Anorexia Nervosa/diagnóstico , Bulimia/diagnóstico , Comorbidade , Diagnóstico Duplo (Psiquiatria) , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Razão de Chances , Prevalência , Probabilidade , Escalas de Graduação Psiquiátrica , Análise de Regressão , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
20.
Am J Psychiatry ; 155(6): 733-40, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9619144

RESUMO

OBJECTIVE: DSM-IV indicates that diagnoses of substance dependence should be further characterized with regard to the presence of a physiological component, defined by tolerance or withdrawal. This study evaluated the possible meaning of this distinction in alcohol-dependent men and women. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were carried out with 3,395 DSM-III-R-defined alcohol-dependent individuals divided into 2,949 subjects (86.9%) with evidence of tolerance and/or withdrawal (group 1), 51.3% of whom evidenced withdrawal symptoms, and 446 subjects (13.1%) without a physiological component (group 2). Data were evaluated to determine differences between the two groups. RESULTS: Group 1 reported greater severity of alcohol dependence as demonstrated by a larger maximum number of drinks in 24 hours, more persons reporting binges, more alcohol-related life problems, more relevant DSM-III-R criteria endorsed, more physiological complications, and more alcohol-related emotional/psychiatric symptoms such as depression and anxiety. Each of these severity indicators for problems in group 1 was significant in the presence of the others in a logistic regression, and similar items remained significant when tolerance alone, withdrawal alone, or their combination was used as the criterion for group 1 membership; however, for withdrawal a larger proportion of the variance was explained by the predictor variables. The regression results were independent of gender, proband status, and history of antisocial personality disorder. CONCLUSIONS: The results support the clinical relevance of distinguishing between alcohol-dependent patients with and without a physiological component. The data indicate a potential advantage to limiting that definition to withdrawal only.


Assuntos
Transtornos Relacionados ao Uso de Álcool/diagnóstico , Alcoolismo/diagnóstico , Síndrome de Abstinência a Substâncias/diagnóstico , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos Relacionados ao Uso de Álcool/fisiopatologia , Bebidas Alcoólicas , Alcoolismo/epidemiologia , Alcoolismo/fisiopatologia , Comorbidade , Diagnóstico Diferencial , Tolerância a Medicamentos , Etanol/efeitos adversos , Feminino , Nível de Saúde , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Índice de Gravidade de Doença , Síndrome de Abstinência a Substâncias/epidemiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Terminologia como Assunto
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