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1.
Bioorg Med Chem Lett ; 29(18): 2690-2694, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31387791

RESUMO

As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

2.
Nicotine Tob Res ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31294817

RESUMO

INTRODUCTION: FTND (FagerstrÓ§m test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. METHODS: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. RESULTS: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. CONCLUSIONS: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. IMPLICATIONS: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

3.
Sci Rep ; 9(1): 7844, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31110189

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

4.
J Med Chem ; 62(10): 5132-5147, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31021617

RESUMO

Previously, we reported a 3-(2-methoxyphenyl)-9-(3-((4-methyl-5-phenyl-4 H-1,2,4-triazol-3-yl)thio)propyl)-3,9-diazaspiro[5.5]undecane (1) compound with excellent dopamine D3 receptor (D3R) affinity (D3R Ki = 12.0 nM) and selectivity (D2R/D3R ratio = 905). Herein, we present derivatives of 1 with comparable D3R affinity (32, D3R Ki = 3.2 nM, D2R/D3R ratio = 60) and selectivity (30, D3R Ki = 21.0 nM, D2R/D3R ratio = 934). Fragmentation of 1 revealed orthosteric fragment 5a to express an unusually low D3R affinity ( Ki = 2.7 µM). Compared to piperazine congener 31, which retains a high-affinity orthosteric fragment (5d, D3R Ki = 23.9 nM), 1 was found to be more selective for the D3R among D1- and D2-like receptors and exhibited negligible off-target interactions at serotoninergic and adrenergic G-protein-coupled receptors (GPCRs), common off-target sites for piperazine-containing D3R scaffolds. This study provides a unique rationale for implementing weakly potent orthosteric fragments into D3R ligand systems to minimize drug promiscuity at other aminergic GPCR sites.

5.
Diabetes Res Clin Pract ; 151: 187-197, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30959150

RESUMO

AIMS: To evaluate the Hypoglycaemia Symptom Rating Questionnaire (HypoSRQ©) and relationships between self-reported hypoglycaemia and hypoglycaemia measured using blinded continuous glucose monitoring (CGM). METHODS: Diabetes outpatients (n = 113) recruited from Ashford and St. Peter's Hospital completed the HypoSRQ (recent weeks version) and provided clinical information. Thirty participants used blinded CGM for six days and completed the HypoSRQ (24-hour version) for seven days, at the end of each week (7-day version), and after four weeks (recent weeks version). RESULTS: The HypoSRQ had a single-factor structure and excellent internal consistency (α = 0.90). There was high correspondence in recalled symptoms, bother ratings and hypoglycaemic episodes across one week and four weeks (r = 0.84-0.98, p < 0.001). HypoSRQ-reported hypoglycaemia correlated significantly with CGM-measured hypoglycaemia (interstitial glucose ≤ 3.9 mmol/l) frequency (r = 0.72, p < 0.001) across six days. The magnitude of the correlation increased when the person's own threshold for detecting hypoglycaemia was used (r = 0.78, p < 0.001). The number of days (out of six) a person reported symptoms of hypoglycaemia was associated with the number of days CGM detected hypoglycaemia (interstitial glucose ≤ 3.9 mmol/l) (r = 0.83, p < 0.001) and remained significant after controlling for covariates. CONCLUSIONS: Psychometric properties of the HypoSRQ make it attractive for use in people with insulin-treated diabetes. The HypoSRQ may be a less-invasive and more-economical alternative to CGM.


Assuntos
Glicemia/metabolismo , Hipoglicemia/diagnóstico , Psicometria/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
6.
J Sch Psychol ; 69: 154-168, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30558750

RESUMO

Recent studies have established connections among teachers' mental health and student outcomes, however there is limited understanding of how these teacher characteristics manifest in the classroom to affect students. The present study informed this gap by examining the associations among third grade teachers' (N = 32) self-reported symptoms of clinical depression and their students' (N = 326) classroom instructional experiences. Eight student experiences described by the Individualizing Student Instruction framework were investigated, including academic instruction facilitated by the teacher in various student groupings, students' independent and group work, teachers' planning/organizing instruction, and students' time off-task and in transitions. Multilevel modeling revealed negative associations between teachers' depressive symptoms and (a) teacher-facilitated academic instruction provided to the whole class and (b) teachers' planning/organizing instruction. Results suggest that teachers experiencing more symptoms may under-utilize instructional approaches that require more effort on their part. We discussed the implications of our findings for students' academic and social-emotional learning, and the potential benefits of incorporating mental health support components into teacher training and professional development aimed at improving instructional practices.

7.
Mar Pollut Bull ; 135: 636-647, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30301083

RESUMO

The Chagos Archipelago is geographically remote and isolated from most direct anthropogenic pressures. Here, we quantify the abundance and diversity of decapod crustaceans inhabiting dead coral colonies, representing a standardised microhabitat, across the Archipelago. Using morphological and molecular techniques we recorded 1868 decapods from 164 nominal species within 54 dead coral colonies, but total species estimates (Chao1 estimator) calculate at least 217 species. Galatheids were the most dominant taxa, though alpheids and hippolytids were also very abundant. 32% of species were rare, and 46% of species were found at only one atoll. This prevalence of rarer species has been reported in other cryptofauna studies, suggesting these assemblages maybe comprised of low-abundance species. This study provides the first estimate of diversity for reef cryptofauna in Chagos, which will serve as a useful baseline for global comparisons of coral reef biodiversity.

8.
AIDS Patient Care STDS ; 32(10): 399-407, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30277816

RESUMO

Women account for 25% of all people living with HIV and 19% of new diagnoses in the United States. African American (AA) women are disproportionately affected. Yet, differences in the care continuum entry are not well understood between patient populations and healthcare sites. We aim to examine gender differences in diagnosis and linkage to care (LTC) in the Expanded HIV Testing and Linkage to Care (X-TLC) program within healthcare settings. Data were collected from 14 sites on the South and West sides of Chicago. Multivariate logistic regression analysis was used to determine the differences in HIV diagnoses and LTC by gender and HIV status. From 2011 to 2016, X-TLC performed 281,017 HIV tests; 63.7% of those tested were women. Overall HIV seroprevalence was 0.57%, and nearly one third (29.4%) of HIV-positive patients identified were cisgender women. Of newly diagnosed HIV-positive women, 89% were AA. 58.5% of new diagnoses in women were made at acute care hospitals, with the remainder at community health centers. Women who were newly diagnosed had a higher baseline CD4 count at diagnosis compared with men. Overall, women had lower odds of LTC compared with men (adjusted odds ratio = 0.58, 95% confidence interval 0.44-0.78) when controlling for patient demographics and newly versus previously diagnosed HIV status. Thus, interventions that focus on optimizing entry into the care continuum for AA women need to be explored.

9.
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.

10.
ACS Chem Neurosci ; 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30010318

RESUMO

We have previously reported on the ability of arylamide phenylpiperazines to bind selectively to the D3 versus the D2 dopamine receptor subtype. For these studies, we used LS-3-134 as the prototypic arylamide phenylpiperazine ligand because it binds with high affinity at D3 dopamine receptor (0.17 nM) and exhibits >150-fold D3 vs D2 receptor binding selectivity. Our goal was to investigate how the composition and size of the nonaromatic ring structure at the piperazine position of substituted phenylpiperazine analogues might influence binding affinity at the human D2 and D3 dopamine receptors. Two factors were identified as being important for determining the binding affinity of bitropic arylamide phenylpiperazines at the dopamine D3 receptor subtype. One factor was the strength of the salt bridge between the highly conserved residue Asp3.32 with the protonated nitrogen of the nonaromatic ring at the piperazine position. The second factor was the configuration of the unbound ligand in an aqueous solution. These two factors were found to be related to the logarithm of the affinities using a simple correlation model, which could be useful when designing high affinity subtype selective bitropic ligands. While this model is based upon the interaction of arylamide phenylpiperazines with the D2 and D3 D2-like dopamine receptor subtypes, it provides insights into the complexity of the factors that define a bitropic mode of the binding at GPCRs.

11.
Ecol Evol ; 8(8): 4098-4107, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29721283

RESUMO

Coral reefs are the most biodiverse marine ecosystem and one of the most threatened by global climate change impacts. The vast majority of diversity on reefs is comprised of small invertebrates that live within the reef structure, termed the cryptofauna. This component of biodiversity is hugely understudied, and many species remain undescribed. This study represents a rare analysis of assembly processes structuring a distinct group of cryptofauna, the Palaemonidae, in the Chagos Archipelago, a reef ecosystem under minimal direct human impacts in the central Indian Ocean. The Palaemonidae are a diverse group of Caridae (infraorder of shrimps) that inhabit many different niches on coral reefs and are of particular interest because of their varied habitat associations. Phylogenetic and trait diversity and phylogenetic signal were used to infer likely drivers of community structure. The mechanisms driving palaemonid community assembly and maintenance in the Chagos Archipelago showed distinct spatial patterns. At local scales, among coral colonies and among reefs fringing individual atolls, significant trait, and phylogenetic clustering patterns suggest environmental filtering may be a dominant ecological process driving Palaemonidae community structure, although local competition through equalizing mechanisms may also play a role in shaping the local community structure. Importantly, we also tested the robustness of phylogenetic diversity to changes in evolutionary information as multi-gene phylogenies are resource intensive and for large families, such as the Palaemonidae, are often incomplete. These tests demonstrated a very modest impact on phylogenetic community structure, with only one of the four genes (PEPCK gene) in the phylogeny affecting phylogenetic diversity patterns, which provides useful information for future studies on large families with incomplete phylogenies. These findings contribute to our limited knowledge of this component of biodiversity in a marine locality as close to undisturbed by humans as can be found. It also provides a rare evaluation of phylogenetic diversity methods.

12.
Sch Psychol Q ; 33(4): 547-560, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29792495

RESUMO

Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development and a model-building approach, the authors examined direct and indirect associations between first-grade (G1) classroom-level adversity (CLA), G1 teaching practices, and student (N = 1,073; M = 6.64 years; 49% girls; 82% White) academic skills and executive functioning in G1 and third grades (G3). Teachers reported the prevalence of adversity among their students (e.g., poor home/family life, poor academic/social readiness). Observers rated G1 teaching practices: teachers' classroom management, controlling instruction, and amount of academic instruction (classroom observation system). Children completed literacy and math assessments at 54 months, G1, and G3 (Woodcock Johnson Letter-Word Identification and Applied Problems), and executive functioning at G1 and G3 (Tower of Hanoi). Direct associations emerged between CLA and controlling instruction (positive), classroom management, and academic instruction (both negative). In addition, CLA was related to G1 literacy (but not math) directly and indirectly via classroom management (negatively) and controlling instruction (positively). The addition of G3 outcomes revealed a negative direct longitudinal association between CLA and G3 executive functioning, and indirect associations with G3 literacy and math through G1 teaching practices and literacy. Results support the notion that collective student characteristics influence student outcomes in part through teaching practices and suggest that teachers and students may benefit from the diffusion of high-adversity classroom compositions when possible. Moreover, in high-adversity classrooms teachers and students may benefit from supports targeting classroom management and foundational student competencies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

13.
Int J Epidemiol ; 47(4): 1098-1105, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29509885

RESUMO

Background: Observational studies have shown that tobacco and alcohol use co-occur, but it is not clear whether this relationship is causal. Methods: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank, we used observational methods to test the hypothesis that smoking heaviness increases alcohol consumption. Mendelian randomization (MR) analyses were then used to test the causal relationship between smoking heaviness and alcohol consumption using 55 967 smokers from four European studies [ALSPAC, The Nord-Trøndelag Health Study (HUNT), the Copenhagen General Population Study (CGPS) and UK Biobank]. MR analyses used rs1051730/rs16969968 as a genetic proxy for smoking heaviness. Results: Observational results provided evidence of an association between cigarettes per day and weekly alcohol consumption (increase in units of alcohol per additional cigarette smoked per day = 0.10, 95% confidence interval (CI) 0.05 to 0.15, P ≤ 0.001 in ALSPAC; and 0.48, 95% CI 0.45 to 0.52, P ≤ 0.001 in UK Biobank). However, there was little evidence for an association between rs1051730/rs16969968 and units of alcohol consumed per week across ALSPAC, HUNT, CGPS and UK Biobank (standard deviation increase in units of alcohol per additional copy of the risk allele = -0.004, 95% CI -0.023 to 0.016, P=0.708, I2 = 51.9%). We had 99% and 88% power to detect a change of 0.03 and 0.02 standard deviation units of alcohol per additional copy of the risk allele, respectively. Conclusions: Previously reported associations between smoking and alcohol are unlikely to be causal, and may be the result of confounding and/or reverse causation. This has implications for public health research and intervention research.

14.
Sci Rep ; 8(1): 4152, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29515196

RESUMO

Seamounts are proposed to be hotspots of deep-sea biodiversity, a pattern potentially arising from increased productivity in a heterogeneous landscape leading to either high species co-existence or species turnover (beta diversity). However, studies on individual seamounts remain rare, hindering our understanding of the underlying causes of local changes in beta diversity. Here, we investigated processes behind beta diversity using ROV video, coupled with oceanographic and quantitative terrain parameters, over a depth gradient in Annan Seamount, Equatorial Atlantic. By applying recently developed beta diversity analyses, we identified ecologically unique sites and distinguished between two beta diversity processes: species replacement and changes in species richness. The total beta diversity was high with an index of 0.92 out of 1 and was dominated by species replacement (68%). Species replacement was affected by depth-related variables, including temperature and water mass in addition to the aspect and local elevation of the seabed. In contrast, changes in species richness component were affected only by the water mass. Water mass, along with substrate also affected differences in species abundance. This study identified, for the first time on seamount megabenthos, the different beta diversity components and drivers, which can contribute towards understanding and protecting regional deep-sea biodiversity.

15.
Int J Ment Health Nurs ; 27(1): 106-115, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28042908

RESUMO

The application of sensory modulation approaches in mental health settings is growing in recognition internationally. However, a number of barriers have been identified as limiting the implementation of the approach, including workplace culture and a lack of accessible and effective sensory approaches training. The aim of this project was to investigate the efficacy of providing this training through a custom-designed e-learning package. Participants in the present study were predominately nurses and occupational therapists working in mental health settings in Queensland, Australia. Data were collected from 121 participants using an online survey. Significant improvements were found between pre- and post-training in participants' real and perceived levels of knowledge, their perceived levels of confidence, and their attitudes towards using sensory modulation approaches in mental health settings. The findings of the study suggest that the custom-designed sensory approaches e-learning package is an effective, accessible, acceptable, and usable method to train health professionals in sensory modulation approaches. As this study is the first to analyse the efficacy of an e-learning sensory approaches package, the results are considered preliminary, and further investigation is required.


Assuntos
Educação a Distância/métodos , Terapia Ocupacional/educação , Enfermagem Psiquiátrica/educação , Sensação , Adulto , Idoso , Avaliação Educacional , Feminino , Humanos , Masculino , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Queensland , Inquéritos e Questionários , Adulto Jovem
16.
J Med Chem ; 60(23): 9905-9910, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29125762

RESUMO

A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 12-25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.


Assuntos
Antagonistas de Dopamina/química , Antagonistas de Dopamina/farmacologia , Receptores de Dopamina D3/antagonistas & inibidores , Alcanos/química , Alcanos/farmacologia , Animais , Linhagem Celular , Humanos , Ligantes , Piperazinas/química , Piperazinas/farmacologia , Ensaio Radioligante , Receptores de Dopamina D3/metabolismo , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Relação Estrutura-Atividade
17.
JAMA Psychiatry ; 74(12): 1242-1250, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28979981

RESUMO

Importance: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. Objectives: To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Design, Setting, and Participants: Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). Main Outcome and Measures: This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. Results: The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = -0.52, P = .005) was detected. Conclusions and Relevance: The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.


Assuntos
Transtorno da Personalidade Antissocial , Transtorno da Conduta , Adolescente , Adulto , Transtorno da Personalidade Antissocial/epidemiologia , Transtorno da Personalidade Antissocial/genética , Transtorno da Personalidade Antissocial/psicologia , Criança , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/genética , Transtorno da Conduta/psicologia , Meio Ambiente , Feminino , Finlândia/epidemiologia , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Fatores Sexuais
18.
J Epidemiol Community Health ; 71(8): 764-770, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28592420

RESUMO

BACKGROUND: Evidence on the role of cannabis as a gateway drug is inconsistent. We characterise patterns of cannabis use among UK teenagers aged 13-18 years, and assess their influence on problematic substance use at age 21 years. METHODS: We used longitudinal latent class analysis to derive trajectories of cannabis use from self-report measures in a UK birth cohort. We investigated (1) factors associated with latent class membership and (2) whether latent class membership predicted subsequent nicotine dependence, harmful alcohol use and recent use of other illicit drugs at age 21 years. RESULTS: 5315 adolescents had three or more measures of cannabis use from age 13 to 18 years. Cannabis use patterns were captured as four latent classes corresponding to 'non-users' (80.1%), 'late-onset occasional' (14.2%), 'early-onset occasional' (2.3%) and 'regular' users (3.4%). Sex, mother's substance use, and child's tobacco use, alcohol consumption and conduct problems were strongly associated with cannabis use. At age 21 years, compared with the non-user class, late-onset occasional, early-onset occasional and regular cannabis user classes had higher odds of nicotine dependence (OR=3.5, 95% CI 0.7 to 17.9; OR=12.1, 95% CI 1.0 to 150.3; and OR=37.2, 95% CI 9.5 to 144.8, respectively); harmful alcohol consumption (OR=2.6, 95% CI 1.5 to 4.3; OR=5.0, 95% CI 2.1 to 12.1; and OR=2.6, 95% CI 1.0 to 7.1, respectively); and other illicit drug use (OR=22.7, 95% CI 11.3 to 45.7; OR=15.9, 95% CI 3.9 to 64.4; and OR=47.9, 95% CI 47.9 to 337.0, respectively). CONCLUSIONS: One-fifth of the adolescents in our sample followed a pattern of occasional or regular cannabis use, and these young people were more likely to progress to harmful substance use behaviours in early adulthood.


Assuntos
Cannabis , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Feminino , Humanos , Masculino , Razão de Chances , Medição de Risco , Autorrelato , Reino Unido
19.
Drug Alcohol Depend ; 178: 143-149, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28647682

RESUMO

BACKGROUND: Smoking influences body weight, but there is little evidence as to whether body mass index (BMI) and body dissatisfaction increase smoking initiation in adolescents. METHODS: We evaluated the association between measured BMI, body dissatisfaction and latent classes of smoking initiation (never smokers, experimenters, late onset regular smokers, early onset regular smokers) in the Avon Longitudinal Study of Parents and Children. In observational analyses we used BMI (N=3754) and body dissatisfaction at age 10.5 years (N=3349). In Mendelian randomisation (MR) analysis, we used a BMI genetic risk score of 76 single nucleotide polymorphisms (N=4017). RESULTS: In females, higher BMI was associated with increased odds of early onset regular smoking (OR: 1.11, 95% CI: 1.04, 1.18) compared to being a never smoker, but not clearly associated with experimenting with smoking (OR: 1.04, 95% CI: 0.99, 1.10) or late onset regular smoking (OR: 1.01, 95% CI: 0.94, 1.09). No clear evidence was found for associations between BMI and smoking initiation classes in males (p-value for sex interaction≤0.001). Body dissatisfaction was associated with increased odds of late-onset regular smoking (OR: 1.71, 95% CI: 1.32, 1.99) in males and females combined (P-value for sex interaction=0.32). There was no clear evidence for an association between the BMI genetic risk score and smoking latent classes in males or females but estimates were imprecise. CONCLUSIONS: BMI in females and body dissatisfaction in males and females are associated with increased odds of smoking initiation, highlighting these as potentially important factors for consideration in smoking prevention strategies.


Assuntos
Comportamento do Adolescente/psicologia , Imagem Corporal/psicologia , Índice de Massa Corporal , Fumar Tabaco/tendências , Adolescente , Peso Corporal/fisiologia , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Pais/psicologia , Fatores de Risco
20.
Addiction ; 112(3): 477-485, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27743424

RESUMO

AIMS: We investigate the extent of and factors associated with denial of previously reported cannabis and other illicit drug use, and assess the potential of hair testing for measuring substance use in general population samples. DESIGN: Birth cohort study. SETTING: United Kingdom, 1991-present. PARTICIPANTS: A total of 3643 participants who provided hair and self-report measures of cannabis and other illicit drug use in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18 years. MEASUREMENTS: Denial of ever use of cannabis and other illicit drugs at age 18 following previously reported use. Positive hair drug tests for cannabis and other illicit drugs, and expected numbers of false positives and false negatives based on expected sensitivity and specificity. FINDINGS: Cannabis and other illicit drug use was reported by 1223 and 393 individuals, respectively, before age 18 years. Of these 176 (14.4%) and 99 (25.2%), respectively, denied use at age 18. Denial of cannabis use decreased with the reporting of other substances and antisocial behaviour. Cannabis and other illicit drug use at age 18 was reported by 547 (22.5%) and 203 (8.4%) individuals, respectively. Of these, 111 (20.3%) and 13 (6.4%) were hair-positive for cannabis and other illicit drugs, respectively. Based on hair testing for cannabis use we expect 0 [95% confidence interval (CI) = 0-169] false positives and 394 (95% CI = 323-449) false negatives compared to observed 362 potential false positives and 436 potential false negatives based on self-report. In hair-positive individuals, reporting the use of other substances and antisocial behaviour decreased the odds of a negative self-report. CONCLUSIONS: Hair analysis provides an unreliable marker of substance use in general population samples. People who report more frequent substance use before age 18 are less likely to later deny previous substance use at age 18 than people who report occasional use.


Assuntos
Decepção , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Cabelo/metabolismo , Humanos , Estudos Longitudinais , Autorrelato , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Reino Unido/epidemiologia , Adulto Jovem
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