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
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.