Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 175
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Addiction ; 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31656048

RESUMO

BACKGROUND AND AIMS: Reinforcing value, an index of motivation for a drug, is commonly measured using behavioral economic purchase tasks. State-oriented purchase tasks are sensitive to phasic manipulations, but with heterogeneous methods and findings. The aim of this meta-analysis was to characterize the literature examining manipulations of reinforcing value, as measured by purchase tasks and multiple-choice procedures, to inform etiological models and treatment approaches. METHODS: A random effects meta-analysis of published findings in peer-reviewed articles. Following the PRISMA protocol, studies were gathered through searches in PsycINFO and PubMed/MEDLINE (published as of May 22, 2018). Searches returned 34 unique studies (aggregate sample N = 2,402; average sample size = 68.94) yielding 126 effect sizes. Measurements included change (i.e., Cohen's d) in six behavioral economic indices (intensity, breakpoint, Omax , Pmax , elasticity, crossover point) in relation to six experimental manipulations (cue exposure, stress/negative affect, reinforcer magnitude, pharmacotherapy, behavioral interventions, opportunity cost). RESULTS: Cue exposure (d range = .25 to .44, all ps < .05) and reinforcer magnitude (d = .60; 95% CI = 0.18, 1.01; p < .005) manipulations resulted in significant increases in behavioral economic demand across studies. Stress/negative affect manipulations also resulted in a small, significant increase in Omax (d = .18; 95% CI = 0.01, 0.34; p = .03); all other effect sizes for negative affect/stress were nonsignificant, albeit similar in size (d range = .14 to.18). In contrast, pharmacotherapy (d range = -.37 to -.49; ps < .04), behavioral intervention (d = -.36 to -1.13) and external contingency (d = -1.42; CI = -2.30, -.0.54; p = .002) manipulations resulted in a significant decrease in intensity. Moderators (substance type) explained some of the heterogeneity in findings across meta-analyses. CONCLUSIONS: In behavioral economic studies, purchase tasks and multiple-choice procedures appear to provide indices that are sensitive to manipulations found to influence motivation to consume addictive substances in field experiments.

2.
Psychiatry Res Neuroimaging ; 293: 110986, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31622796

RESUMO

This study examines associations between two measures of impulsivity and brain response to alcohol taste cues. Impulsivity is both a risk factor for and a consequence of alcohol use and misuse. Frontostriatal circuits are linked to both impulsivity and addiction-related behaviors, including response to alcohol cues. Non-treatment-seeking heavy drinkers (n = 55) completed (i) an fMRI alcohol taste cue-reactivity paradigm; (ii) the monetary choice questionnaire (MCQ), a measure of choice impulsivity where participants choose between smaller, sooner rewards and larger, delayed rewards; (iii) and the UPPS-P Impulsive Behavior Scale, a self-report measure assessing five impulsivity factors. General linear models identified associations between neural alcohol taste cue-reactivity and impulsivity, adjusting for age, gender, and smoking status. Self-reported sensation seeking was positively associated with alcohol taste cue-elicited activation in frontostriatal regions, such that individuals who reported higher sensation seeking displayed greater neural response to alcohol taste cues. Conversely, delay discounting was negatively associated with activation in frontoparietal regions, such that individuals who reported greater discounting showed less cue-elicited activation. There were no significant associations between other self-reported impulsivity subscales and alcohol taste cue-reactivity. These results indicate that sensation seeking is associated with reward responsivity, while delay discounting is associated with recruitment of self-control circuitry.

3.
Syst Rev ; 8(1): 230, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484558

RESUMO

BACKGROUND: Heavy episodic drinking (HED) refers to alcohol consumption that exceeds the recommended threshold for a given episode and increases risk for diverse negative alcohol-related consequences. A pattern of weekly HED is most prevalent in emerging adults (i.e., age 18-25). However, rates of HED consistently decline in the mid to late twenties, referred to as 'aging out' or 'maturing out' of HED. Although many individual studies have followed changes in drinking behaviour over the transition to adulthood, there has yet to be a systematic review to identify consistent factors contributing to risk (i.e. failure to age out) and protection (i.e. successful aging out). The objective of this review will be to summarize and critically appraise the literature on factors contributing to aging out of HED among emerging adults. METHODS: A systematic search of observational cohort studies following drinking behaviours in age cohorts overlapping with the emerging adulthood period will be conducted in MEDLINE, EMBASE, PsychInfo, and CINAHL. Two independent reviewers will evaluate identified studies for inclusion eligibility, extract study data, and assess the quality of included studies. Primary outcomes will be quantity/frequency of alcohol use (e.g. drinks/week) and severity of alcohol-related problems. Predictors of maturing out of HED will be reported narratively, and where appropriate, random effects meta-analyses will be conducted to provide pooled effect sizes. An evidence map will be created to characterize the overall pattern of findings. DISCUSSION: This systematic review will provide a timely and warranted summary of published work contributing to understanding aging out of heavy episodic drinking. Our findings will provide critical commentary on the developmental course of HED during the transition from adolescence to adulthood and will be the first review to consider both protective and risk factors for maturing out of frequent binge drinking. By highlighting factors identifying those at-risk for prolonged heavy episodic drinking, our conclusions will have important treatment implications for primary, secondary, and tertiary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017078436 .

4.
Artigo em Inglês | MEDLINE | ID: mdl-31556676

RESUMO

The Cigarette Purchase Task (CPT) affords a high-resolution index of the reinforcing efficacy of nicotine. Although a high number and steep progression of prices have traditionally been used, attention is now placed on developing brief measures of this task. This study sought to assess the psychometric properties of a brief CPT for assessing cigarette demand in treatment-seeking smokers with and without depressive symptoms. The study sample comprised 360 participants (210 with and 150 without depressive symptomatology). We tested the effect of different CPT price densities (14-19) on the variation of CPT indices and provided a thorough assessment of its reliability using 2 different approaches: the classical test theory and item response theory models. Reliability analyses indicated that the 14-item CPT performed the best in terms of reliability across study samples. The CPT's information functions for this shortened version yielded the highest precision at medium levels of the measured construct (for theta values between -0.4 and 0.4). Omax (nondepressed: discrimination parameter a = 14.66; depressed smokers: a = 6.73) and elasticity (nondepressed: a = -3.89; depressed smokers; a = -2.97) best discriminated between patients with different levels of cigarette demand. Results support the utility of item response theory to evaluate the precision of the CPT for different levels of the reinforcing efficacy of nicotine. A 14-item CPT stands as a reliable and efficient method for research and clinical purposes. This task performs particularly well with depressed and nondepressed smokers endorsing moderate levels of the CPT construct. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

5.
Alcohol Clin Exp Res ; 43(9): 1918-1927, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365137

RESUMO

BACKGROUND: Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol-related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences. METHODS: This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; Mage  = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting). RESULTS: Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow-up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men. CONCLUSIONS: This study adds to the understanding of brain correlates of alcohol use in a large, gender-balanced sample of younger adults. Although the cross-sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations.

6.
Addict Behav ; 98: 106044, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31330464

RESUMO

INTRODUCTION: The Alcohol Purchase Task (APT), a behavioral economic measure of alcohol's reinforcing value (demand), has been used to predict the effects of Brief Motivational Intervention (BMI) on alcohol use outcomes. However, it is not known whether BMI may be more or less efficacious, relative to control, among those with different levels of alcohol demand prior to treatment. METHODS: Non college-attending young adults (N = 150) reporting past-month heavy drinking were randomized to a single in-person session of BMI or a relaxation training control (REL). The BMI included delivery of personalized feedback and focused on developing discrepancy between the young adults' goals and their current pattern of alcohol use. At baseline, participants completed assessments of alcohol use and the APT. Drinking levels were re-assessed at 6 weeks and 3 months post-intervention. Demand indices derived from the APT were examined as moderators of treatment effects on follow-up drinking after covarying for baseline alcohol use. RESULTS: Two of four APT demand indices - intensity and Omax - moderated treatment outcomes. Relative to REL, BMI led to greater reductions in total number of drinks consumed and drinks per drinking day among participants with higher baseline alcohol demand. This association was not observed among participants with lower levels of alcohol demand. CONCLUSIONS: These results demonstrate that BMI may be particularly beneficial for those with a high reinforcing value of alcohol. The mechanism for this effect is unclear, and determining the process by which BMI confers increased benefit for these individuals is a fruitful area for future work.

7.
Addiction ; 114(11): 1926-1940, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31313403

RESUMO

BACKGROUND AND AIMS: A cigarette purchase task (CPT) aims to characterize individual variation in the reinforcing value of tobacco. This meta-analysis estimated the associations between cigarette demand, tobacco consumption and nicotine dependence using this task. DESIGN: A meta-analysis of cross-sectional studies identified by PubMed and PsycINFO databases was conducted. Fixed- and random-effects models were used. The study also examined the model used to derive elasticity of demand (exponential or exponentiated) as a potential moderator. Publication bias was assessed using 'fail-safe N', Begg-Mazumdar test, Egger's test, Tweedie's trim-and-fill approach and meta-regression of publication year with effect size. SETTING: Studies from any setting that reported coefficient correlations on the tested associations. PARTICIPANTS: Daily cigarette users (i.e. 5 to 38 cigarettes per day; n = 7649). MEASUREMENTS: Cigarette consumption, nicotine dependence and five tobacco demand indicators: intensity (i.e. consumption at no cost), elasticity (i.e. sensitivity to rises in costs), Omax (maximum expenditure), Pmax (i.e. price at which consumption becomes elastic) and breakpoint (i.e. price at which consumption ceases). FINDINGS: Twenty-three studies met inclusion criteria. All the CPT indices were significantly correlated with smoking behavior (rs = 0.044-0.572, Ps = 0.012-10-8 ). Medium-to-large effect size associations were present for intensity, Omax, and elasticity, whereas small effects were obtained for breakpoint and Pmax . Evidence of a moderating effect of the different elasticity modeling approaches was not present. There was limited evidence of publication bias. CONCLUSIONS: All five demand indices derived from the cigarette purchase task by (CPT) were robustly associated with cigarette consumption and tobacco dependence. Of the demand indices, maximum expenditure, intensity and elasticity exhibited the largest magnitude associations.

8.
Addict Behav ; 98: 106055, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31357071

RESUMO

BACKGROUND: Continuing care is increasingly prioritized in the treatment of substance use disorders (SUDs). Ongoing engagement in continuing care, including mutual support (e.g., 12-step groups) and/or professional outpatient services, may enhance treatment outcomes and facilitate recovery. OBJECTIVE: This study investigates how engagement in 12-step mutual support and professional outpatient services is associated with short-term substance use outcomes in a sample of patients who completed inpatient SUDs treatment. METHODS: As part of the Recovery Journey Project - a longitudinal cohort study - participants completed questionnaires upon admission to an inpatient SUDs treatment program, and at 1- and/or 3-months post-discharge (n = 379). Baseline data were collected by self-administered, electronic questionnaires. Follow up data were collected by phone or email. Analyses involved multivariate Generalized Estimating Equations separately modelling self-reported abstinence and percent days abstinent (PDA) over the three time periods. RESULTS: Overall, rates of self-reported abstinence and PDA increased significantly from baseline to 1- and 3-months follow up. Engagement in 12-step activities (i.e., attended 30 meetings in 30 days, had a home group, had a sponsor, did service work) and professional outpatient substance use support were each significantly associated with abstinence and PDA. Participants who reported a higher degree of 12-step involvement (defined as engagement in more 12-step activities) were also more likely to report being abstinence and greater PDA. CONCLUSIONS: Engagement in continuing care, including 12-step activities and professional outpatient substance use support, was highly associated with substance use. Clinical teams should encourage participation in such activities to optimize treatment outcomes.

9.
Behav Sci Law ; 37(4): 435-451, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31268203

RESUMO

Deficits in impulse control have been linked to criminal offending, risk of recidivism, and other maladaptive behaviours relevant to the criminal justice system (e.g. substance use). Impulse control can be conceptualized as encompassing the broad domains of response inhibition and impulsive/risky decision-making. Advancements in technology have led to the development of computerized behavioural measures to assess performance in these domains, such as go/no-go and delay discounting tasks. Despite a relatively large literature examining these tasks in offenders, findings are not universally consistent. This systematic review aims to synthesize the literature using computerized neurocognitive tasks to assess two domains of impulse control in offenders: response inhibition and impulsive/risky decision-making. The review included 28 studies from diverse geographic locations, settings, and offender populations. The results largely support the general conclusion that offenders exhibit deficits in impulse control compared with non-offenders, with studies of response inhibition more consistently reporting differences than studies using impulsive and risky decision-making tasks. Findings are discussed in the context of contemporary neuroimaging research emphasizing dysfunction in prefrontal cortex as a key contributor to impulse control deficits in offenders.


Assuntos
Criminosos , Comportamento Impulsivo , Reincidência , Criminosos/psicologia , Tomada de Decisões , Humanos , Masculino , Transtornos Relacionados ao Uso de Substâncias/psicologia
10.
J Psychiatry Neurosci ; 44(6): 414-422, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31245962

RESUMO

Background: There is evidence that heavy cannabis use is associated with decrements in cognitive performance, but findings are mixed and studies are often limited by small sample sizes and narrow adjustment for potential confounding variables. In a comparatively large sample, the current study examined associations between multiple indicators of cannabis use in relation to performance on a variety of neuropsychological tasks. Methods: Participants were 1121 adults (54% female) enrolled in the Human Connectome Project. Cannabis involvement comprised recent cannabis use (positive tetrahydrocannabinol screen), total number of lifetime uses, cannabis use disorder and age at first use. The neuropsychological battery comprised performance in episodic memory, fluid intelligence, attention, working memory, executive function, impulsive decision-making, processing speed and psychomotor dexterity. Covariates were age, sex, income, family structure and alcohol and tobacco use. Results: Positive urinary tetrahydrocannabinol status was associated with worse performance in episodic memory and processing speed, and positive cannabis use disorder status was associated with lower fluid intelligence (all p < 0.005). No other significant associations were present. Limitations: The sample was limited to young adults aged 22­36 years. The measures of cannabis involvement were relatively coarse. Conclusion: Beyond an array of potential confounders, recent cannabis use was associated with deficits in memory and psychomotor performance, and cannabis use disorder was associated with lower overall cognitive functioning in a large normative sample of adults. The findings pertaining to recent use have particular relevance for occupational settings.

11.
Nat Neurosci ; 22(7): 1196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168101

RESUMO

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

12.
Can J Public Health ; 110(4): 527-528, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31187462

RESUMO

The published version of Fig. 1 contained a mistake in the colour scale for the vertical lines and corresponding labels for the Pmax values.

13.
Exp Clin Psychopharmacol ; 27(4): 383-401, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31120284

RESUMO

Cannabis and its pharmacologically active constituents, phytocannabinoids, have long been reported to have multiple medicinal benefits. One association often reported by users is sedation and subjective improvements in sleep. To further examine this association, we conducted a critical review of clinical studies examining the effects of cannabinoids on subjective and objective measures of sleep. PubMED, Web of Science, and Google Scholar were searched using terms and synonyms related to cannabinoids and sleep. Articles chosen included randomized controlled trials and open label studies. The Cochrane risk of bias tool was used to assess the quality of trials that compared cannabinoids with control interventions. The current literature focuses mostly on the use of tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in the treatment of chronic health conditions such as multiple sclerosis, posttraumatic stress disorder (PTSD), and chronic pain. Sleep is often a secondary, rather than primary outcome in these studies. Many of the reviewed studies suggested that cannabinoids could improve sleep quality, decrease sleep disturbances, and decrease sleep onset latency. While many of the studies did show a positive effect on sleep, there are many limiting factors such as small sample sizes, examining sleep as a secondary outcome in the context of another illness, and relatively few studies using validated subjective or objective measurements. This review also identified several questions that should be addressed in future research. These questions include further elucidation of the dichotomy between the effects of THC and CBD, as well as identifying any long-term adverse effects of medicinal cannabinoid use. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

14.
Child Maltreat ; 24(4): 400-410, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31030539

RESUMO

The aim of the present study was 2-fold: (1) to utilize improved amygdala segmentation and exploratory factor analysis to characterize the latent volumetric structure among amygdala nuclei and (2) to assess the effect of adverse childhood experiences (ACEs) on amygdalar morphometry and current psychiatric symptoms. To investigate these aims, structural (T1) MRI and self-report data were obtained from 119 emerging adults. Regression analysis showed that higher ACE scores were related to reduced volume of the right, but not the left, amygdalar segments. Further, exploratory factor analysis yielded a two-factor structure, basolateral and central-medial nuclei of the right amygdala. Stractual equation modeling analyses revealed that higher ACE scores were significantly related to a reduced volume of the right basolateral and central-medial segments. Furthermore, reduction in the right basolateral amygdala was associated with increased anxiety, depressive symptoms, and alcohol use. This association supports an indirect effect between early adversity and psychiatric problems via reduced right basolateral amygdalar volume. The high-resolution segmentation results reveal a latent structure among amygdalar nuclei, which is consistent with prior work conducted in nonhuman mammals. These findings extend previous reports linking early adversity, right amygdala volume, and psychopathology.

15.
Dev Cogn Neurosci ; 37: 100642, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31004982

RESUMO

Prolonged exposure to socioeconomic hardship (SH) is associated with greater delayed reward discounting (DRD), a form of impulsive decision-making that reflects a reduced capacity to delay gratification and a significant correlate of diverse risk behaviors, but the neurobehavioral mechanisms linking SH and DRD are unknown. An emerging hypothesis suggests that cognitive and affective stress associated with poverty may tax neurocognitive functions, such as working memory (WM), and lead to impulsive DRD. Furthermore, research suggests that emotional reactivity (ER) is an important dispositional factor to consider in the link between executive functions and DRD. Thus, we longitudinally examined the indirect effect of SH on impulsive DRD via a network of brain regions associated with WM function in a sample of young adults, and whether that link was moderated by ER. Participants were 119 rural African Americans (aged 19-24 years) assessed behaviorally on four occasions, with fMRI at the last time point. Results showed that, among emerging adults with higher ER, SH severity was predictive of increased DRD via reduced response in brain regions activated during an n-back WM task. These findings reveal both the cognitive and affective mechanisms that underlie the relationship between SH and DRD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-30998058

RESUMO

Risk-taking behavior can result in a range of maladaptive behaviors such as illicit substance use, unsafe driving, and high-risk sexual behavior. Perception of risk and preference for engaging in risky behaviors have been measured using both self-report measures and a range of behavioral tasks designed for the purpose, and these may predict future risk-taking behavior. However, the interrelationships between these measures and the latent constructs underlying them are poorly understood. In the present study, we examined data from over 1,000 men and women who completed measures of risk-related behaviors, including self-reports of perception of risk, propensity to engage in risky behaviors, and incentivized performance on tasks that involve risk. We conducted principal component analyses (PCAs) to understand the underlying latent structure of these measures. A PCA with the full sample revealed 5 distinct components, corresponding to measures of (a) health/ethical risks, (b) discounting of uncertain rewards, (c) risk of personal finances, (d) preferences in recreational hobbies and social interactions that involve risk, and (e) behavior involving risks in interpersonal interactions. Although we found sex differences on several of the measures, the sex-adjusted PCA components were similar to those of the unadjusted full sample PCA. These findings add to a growing literature revealing different components of the broad category of risk perception and risk-taking behaviors. A better understanding of the multidimensionality of risk preference will help lay the foundation for more refined measures, develop better predictors of future risk-taking behavior, and ultimately to study the genetic or other biological basis of risk-taking. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

17.
Soc Cogn Affect Neurosci ; 14(4): 381-395, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-30848280

RESUMO

This study is a replication of an existing large study (N = 507) on the surface-based morphometric correlates of five-factor model (FFM) personality traits. The same methods were used as the original study in another large sample drawn from the same population (N = 597) with results then being aggregated from both samples (N = 1104), providing the largest investigation into the neuroanatomical correlates of FFM personality traits to date. Clusters of association between brain morphometry and each FFM trait are reported. For neuroticism, agreeableness, openness and conscientiousness clusters of association were found in the dorsolateral prefrontal cortex for at least one morphometric index. Morphometry in various other regions was also associated with each personality trait. While some regions found in the original study were confirmed in the replication and full samples, others were not, highlighting the importance of replicating even high-quality, well-powered studies. Effect sizes were very similar in the replication and whole samples as those found in the original study. As a whole, the current results provide the strongest evidence to date on the neuroanatomical correlates of personality and highlights challenges in using this approach to understanding the neural correlates of personality.

18.
Behav Processes ; 162: 157-161, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30876880

RESUMO

Delayed reward discounting (DRD) is a behavioral economic measure of impulsivity, reflecting how rapidly a reward loses value based on its temporal distance. In humans, more impulsive DRD is associated with susceptibility to a number of psychiatric diseases (e.g., addiction, ADHD), health outcomes (e.g., obesity), and lifetime outcomes (e.g., educational attainment). Although the determinants of DRD are both genetic and environmental, this review focuses on its genetic basis. Both rodent studies using inbred strains and human twin studies indicate that DRD is moderately heritable, a conclusion that was further supported by a recent human genome-wide association study (GWAS) that used single nucleotide polymorphisms (SNP) to estimate heritability. The GWAS of DRD also identified genetic correlations with psychiatric diagnoses, health outcomes, and measures of cognitive performance. Future research priorities include rodent studies probing putative genetic mechanisms of DRD and human GWASs using larger samples and non-European cohorts. Continuing to characterize genomic influences on DRD has the potential to yield important biological insights with implications for a variety of medically and socially important outcomes.


Assuntos
Desvalorização pelo Atraso , Genômica , Comportamento Impulsivo , Recompensa , Animais , Comportamento Aditivo , Economia Comportamental , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único
19.
J Neurosci ; 39(13): 2562-2572, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30718321

RESUMO

Impulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse and attention-deficit/hyperactivity disorder (ADHD). In collaboration with the genetics company 23andMe, we performed 10 genome-wide association studies on measures of impulsive personality traits [the short version of the UPPS-P Impulsive Behavior Scale, and the Barratt Impulsiveness Scale (BIS-11)] and drug experimentation (the number of drug classes an individual had tried in their lifetime) in up to 22,861 male and female adult human research participants of European ancestry. Impulsive personality traits and drug experimentation showed single nucleotide polymorphism heritabilities that ranged from 5 to 11%. Genetic variants in the CADM2 locus were significantly associated with UPPS-P Sensation Seeking (p = 8.3 × 10-9, rs139528938) and showed a suggestive association with Drug Experimentation (p = 3.0 × 10-7, rs2163971; r 2 = 0.68 with rs139528938). Furthermore, genetic variants in the CACNA1I locus were significantly associated with UPPS-P Negative Urgency (p = 3.8 × 10-8; rs199694726). The role of these genes was supported by single variant, gene- and transcriptome-based analyses. Multiple subscales from both UPPS-P and BIS showed strong genetic correlations (>0.5) with Drug Experimentation and other substance use traits measured in independent cohorts, including smoking initiation, and lifetime cannabis use. Several UPPS-P and BIS subscales were genetically correlated with ADHD (r g = 0.30-0.51), supporting their validity as endophenotypes. Our findings demonstrate a role for common genetic contributions to individual differences in impulsivity. Furthermore, our study is the first to provide a genetic dissection of the relationship between different types of impulsive personality traits and various psychiatric disorders.SIGNIFICANCE STATEMENT Impulsive personality traits (IPTs) are heritable traits that are governed by frontal-subcortical circuits and are associated with neuropsychiatric disorders, particularly substance use disorders. We have performed genome-wide association studies of IPTs to identify regions and genes that account for this heritable variation. IPTs and drug experimentation were modestly heritable (5-11%). We identified an association between single nucleotide polymorphisms in CADM2 and both sensation seeking and drug experimentation; and between variants in CACNA1I and negative urgency. The role of these genes was supported by single variant, gene- and transcriptome-based analyses. This study provides evidence that impulsivity can be genetically separated into distinct components. We showed that IPT are genetically associated with substance use and ADHD, suggesting impulsivity is an endophenotype contributing to these psychiatric conditions.

20.
Neuropsychopharmacology ; 44(3): 613-619, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30644440

RESUMO

Worldwide, cannabis is one of the most widely used psychoactive substances and cannabis use has been implicated in poorer performance in several cognitive domains, including working memory (WM). However, the neural mechanisms underlying these WM decrements are not well understood and the current study investigated the association of cannabis involvement with WM performance and associated neural activation in the Human Connectome Project (N = 1038). Multiple indicators of cannabis involvement were examined in relation to behavioral performance and brain activity in a visual N-back task using functional magnetic resonance imaging. A positive urine drug screen for tetrahydocannabinol (THC+ status), the principal psychoactive constituent in cannabis, was associated with worse WM performance and differential brain response in areas previously linked to WM performance. Furthermore, decreases in blood-activation-level-dependent (BOLD) signal in WM task-positive brain regions and increases in task-negative regions mediated the relationship between THC+ status and WM performance. In contrast, WM performance and BOLD response during the N-back task were not associated with total lifetime cannabis use, age of first use, or other indicators of involvement, suggesting that the effects of cannabis on WM were short-term residual effects, rather than long-term persistent effects. These findings elucidate differential influences of cannabis involvement on neurocognition and have significant potential implications for occupational performance in diverse settings.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA