RESUMO
To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.
Assuntos
Analgésicos Opioides/administração & dosagem , Comportamento Aditivo/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Genômica , Transtornos Relacionados ao Uso de Opioides/genética , Analgésicos Opioides/farmacologia , Feminino , Genoma Humano/genética , Humanos , Masculino , Herança Multifatorial/genéticaRESUMO
BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.
Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Análise Serial de Tecidos , GencitabinaRESUMO
OBJECTIVE: This study examined 12-month rates of service use for mental, emotional, and behavioral disorders among adolescents. METHODS: Data were from the National Comorbidity Survey Adolescent Supplement (NCS-A), a survey of DSM-IV mental, emotional, and behavioral disorders and service use. RESULTS: In the past 12 months, 45.0% of adolescents with psychiatric disorders received some form of service. The most likely were those with ADHD (73.8%), conduct disorder (73.4%), or oppositional defiant disorder (71.0%). Least likely were those with specific phobias (40.7%) and any anxiety disorder (41.4%). Among those with any disorder, services were more likely to be received in a school setting (23.6%) or in a specialty mental health setting (22.8%) than in a general medical setting (10.1%). Youths with any disorder also received services in juvenile justice settings (4.5%), complementary and alternative medicine (5.3%), and human services settings (7.9%). Although general medical providers treated a larger proportion of youths with mood disorders than with behavior disorders, they were more likely to treat youths with behavior disorders because of the larger number of the latter (11.5% of 1,465 versus 13.9% of 820). Black youths were significantly less likely than white youths to receive specialty mental health or general medical services for mental disorders. CONCLUSIONS: Findings from this analysis of NCS-A data confirm those of earlier, smaller studies, that only a minority of youths with psychiatric disorders receive treatment of any sort. Much of this treatment was provided in service settings in which few providers were likely to have specialist mental health training.
Assuntos
Serviços de Saúde do Adolescente/estatística & dados numéricos , Transtornos Mentais/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Serviços de Saúde Escolar/estatística & dados numéricos , Adolescente , Comorbidade , Feminino , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Masculino , Transtornos Mentais/epidemiologia , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: Study 1: Introduce and validate a method for measuring EBV p18-VCA antibodies in whole blood spots to provide a minimally invasive marker of cell-mediated immune function. Study 2: Apply this method to a large community-based study of psychopathology in children and adolescents. METHODS: The EBV antibody method was evaluated through analysis of precision, reliability, stability, and comparisons with plasma and indirect immunofluorescence methods. The effects of life events on p18-VCA antibody level were considered in a subsample of 9, 11, and 13 year-old children participating in the Great Smoky Mountains Study in North Carolina. The subsample was stratified by age, sex, and degree of overall life strain. RESULTS: Dried blood spots provided a convenient, sensitive, precise, and reliable method for measuring EBV p18-VCA antibody titer. Life events were positively associated with p18-VCA antibodies in girls but not in boys. CONCLUSIONS: The validity of the blood spot EBV p18-VCA antibody assay, as well as the ease of sample collection, storage, and transportation, may provide an opportunity for psychoneuroimmunology to explore a wider range of stress models in larger, community-based studies.
Assuntos
Anticorpos Antivirais/sangue , Proteínas do Capsídeo , Herpesvirus Humano 4/imunologia , Imunidade Celular/imunologia , Transtornos Psicofisiológicos/imunologia , Adolescente , Antígenos Virais/imunologia , Coleta de Amostras Sanguíneas , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Projetos Piloto , Psiconeuroimunologia , Transtornos Psicofisiológicos/diagnóstico , Transtornos Psicofisiológicos/psicologia , Fatores SexuaisRESUMO
Dialectical behavior therapy, an outpatient psychosocial treatment for chronically suicidal women with borderline personality disorder, has been adapted for use in a partial hospital program for women. Patients attend the program for a minimum of five days of individual and group therapy, and full census is 12 women. About 65 percent of participants meet at least three criteria for borderline personality disorder, and most have suicidal and self-injurious behavior. Their comorbid diagnoses include trauma-related diagnoses and anxiety disorders, severe eating disorders, substance abuse, and depression. The partial hospital program is linked to an aftercare program offering six months of outpatient skills training based on dialectical behavior therapy. Both programs focus on teaching patients four skills: mindfulness (attention to one's experience), interpersonal effectiveness, emotional regulation, and distress tolerance. Two years of operation of the women's partial hospital program provides promising anecdotal evidence that dialectical behavioral therapy, an outpatient approach, can be effectively modified for partial hospital settings and a more diverse population.
Assuntos
Terapia Comportamental/métodos , Transtorno da Personalidade Borderline/terapia , Psicoterapia Breve/métodos , Prevenção do Suicídio , Adulto , Assistência ao Convalescente/métodos , Transtorno da Personalidade Borderline/psicologia , Hospital Dia , Feminino , Hospitais Psiquiátricos , Humanos , Pessoa de Meia-Idade , Ambulatório Hospitalar , Rhode Island , Serviços de Saúde da MulherRESUMO
Nondirective (ND), applied relaxation (AR), and cognitive behavioral (CBT) therapies for generalized anxiety disorder (GAD) were compared. The latter 2 conditions were generally equivalent in outcome but superior to ND at postassessment. The 3 conditions did not differ on several process measures, and ND created the greatest depth of emotional processing. Follow-up results indicated losses in gains in ND, maintained gains in the other 2 conditions, especially CBT, and highest endstate functioning for CBT. AR and CBT thus contain active ingredients in the treatment of GAD; support exists for further development of imagery exposure methods or cognitive therapy because of their likely role in promoting maintenance of change with this disorder. Expectancy for improvement was also associated with outcome, suggesting the need for further research on this construct for understanding the nature of GAD and its amelioration.