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Objective: To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype., Method: Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a class of individuals with elevated behavioral and emotional difficulties ("dysregulated"; n = 233) who were compared to a matched sample from a low symptom class (controls, n = 233). Whole-brain gray matter volume (GMV) images were compared using a general linear model with 10,000 random label permutations. Regional GMV findings were then probed for functional differences from three functional magnetic resonance imaging (fMRI) tasks. Significant brain features then informed mediation path models linking the likelihood of psychiatric disorders (DSM-IV) with dysregulation., Results: Whole-brain differences were found in the right orbitofrontal cortex (R.OFC; p < .05; k = 48), with dysregulated individuals exhibiting lower GMV. The dysregulated group also exhibited higher activity in this region during successful inhibitory control (F 1,429  = 7.53, p < .05). Path analyses indicated significant direct effects between the likelihood of psychopathologies and dysregulation. Modeling the R.OFC as a mediator returned modest partial effects, suggesting that the path linking the likelihood of an anxiety or conduct disorder diagnoses to dysregulation is partially explained by this anatomical feature., Conclusion: A large sample of dysregulated adolescents exhibited lower GMV in the R.OFC relative to controls. Dysregulated individuals also exhibited higher regional activations when exercising inhibitory control at performance levels comparable to those of controls. These findings suggest a neurobiological marker of dysregulation and highlight the role of the R.OFC in impaired emotional and behavioral control., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Cannabis use initiated during adolescence might precipitate negative consequences in adulthood. Thus, predicting adolescent cannabis use prior to any exposure will inform the aetiology of substance abuse by disentangling predictors from consequences of use. In this prediction study, data were drawn from the IMAGEN sample, a longitudinal study of adolescence. All selected participants (n = 1,581) were cannabis-naïve at age 14. Those reporting any cannabis use (out of six ordinal use levels) by age 16 were included in the outcome group (N = 365, males n = 207). Cannabis-naïve participants at age 14 and 16 were included in the comparison group (N = 1,216, males n = 538). Psychosocial, brain and genetic features were measured at age 14 prior to any exposure. Cross-validated regularized logistic regressions for each use level by sex were used to perform feature selection and obtain prediction error statistics on independent observations. Predictors were probed for sex- and drug-specificity using post-hoc logistic regressions. Models reliably predicted use as indicated by satisfactory prediction error statistics, and contained psychosocial features common to both sexes. However, males and females exhibited distinct brain predictors that failed to predict use in the opposite sex or predict binge drinking in independent samples of same-sex participants. Collapsed across sex, genetic variation on catecholamine and opioid receptors marginally predicted use. Using machine learning techniques applied to a large multimodal dataset, we identified a risk profile containing psychosocial and sex-specific brain prognostic markers, which were likely to precede and influence cannabis initiation., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: A range of school-based prevention programs has been developed and used to prevent, delay, or reduce alcohol use among adolescents. Most of these programs have been evaluated at the community-level impact. However, the effect of contextual risk factors has rarely been considered in the evaluation of these programs. The aim of this study was to investigate the potential moderating effects of 2 important contextual risk factors (i.e., socioeconomic status [SES] and peer victimization) on the effectiveness of the school-based personality-targeted interventions (Preventure program) in reducing adolescent alcohol use over a 2-year period using a cluster-randomized trial., Methods: High-risk adolescents were identified using personality scores on the Substance Use Risk Profile Scale and randomized to intervention and control groups. Two 90-minute cognitive behavioral therapy-based group sessions targeted 1 of 4 personality risk profiles: Anxiety Sensitivity, Hopelessness, Impulsivity, or Sensation Seeking. Multilevel linear modeling of alcohol use, binge drinking, and drinking-related harm was conducted to assess the moderating effect of baseline peer victimization and SES., Results: Results indicated that the Preventure program was equally beneficial to all adolescents, regardless of SES and victimization history, in terms of their alcohol outcomes and related harm. Receiving the intervention was additionally beneficial for adolescents reporting peer victimization regarding their alcohol-related harm compared to nonvictimized youth (β = -0.29, SE = 0.11, p = 0.014)., Conclusions: Findings suggest that the content of personality-targeted interventions is beneficial for all high-risk youth regardless of their SES or experience of peer victimization. The current study suggests that using targeted approaches, such as targeting underlying personality risk factors, may be the most appropriate substance use prevention strategy for high-risk youth, as it is beneficial for all high-risk youth regardless of their contextual risk factors., (© 2019 by the Research Society on Alcoholism.)

Objective: This study aims to identify key process variables that are associated with changes in alcohol consumption and mental health symptoms over 12months following personality-targeted interventions in youth., Method: 154 high-risk youth (aged 12-13years) in 7 Montreal high schools were identified using the Substance Use Risk Profile Scale and participated in personality-matched interventions. Preliminary process variables were identified using a combination of psychotherapy process variables and youth-generated (qualitative) feedback immediately post-intervention., Results: Learning, skill development and a positive group experience were key to positive behavioural change. Youth-generated feedback independently accounted for 12-25% of the variance in the change in alcohol use and mental health symptoms over 12months. Changes in cognitive distortions and self-esteem accounted for somewhat less of the variance in alcohol use (0-9%), but a moderate-to-large portion of the variance in changes in mental health symptoms (up to 44%)., Conclusions: The study findings highlight candidate process variables relevant to future implementations of this program that might inform change processes relevant to brief interventions with youth more generally. This study suggests that youth experiences can indicate proximal measures of program efficacy, and has implications for the dissemination of this brief intervention program. Clinical Trial registered on www.ClinicalTrials.gov, "Does Delaying Adolescent Substance Use Lead to Improved Cognitive Function and Reduce Risk for Addiction", study NCT01655615., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: Substance use and binge drinking during early adolescence are associated with neurocognitive abnormalities, mental health problems and an increased risk for future addiction. The trial aims to evaluate the protective effects of an evidence-based substance use prevention programme on the onset of alcohol and drug use in adolescence, as well as on cognitive, mental health and addiction outcomes over 5 years., Design: Thirty-eight high schools will be recruited, with a final sample of 31 schools assigned to intervention or control conditions (3826 youth). Brief personality-targeted interventions will be delivered to high-risk youth attending intervention schools during the first year of the trial. Control school participants will receive no intervention above what is offered to them in the regular curriculum by their respective schools., Setting: Public/private French and English high schools in Montreal (Canada)., Participants: All grade 7 students (12-13 years old) will be invited to participate. High-risk youth will be identified as those scoring one standard deviation or more above the school mean on one of the four personality subscales of the Substance Use Risk Profile Scale (40-45% youth)., Measurements: Self-reported substance use and mental health symptoms and cognitive functioning measured annually throughout 5 years. Primary outcomes are the onset of substance use disorders at 4 years post-intervention (year 5). Secondary intermediate outcomes are the onset of alcohol and substance use 2 years post-intervention and neuropsychological functions; namely, the protective effects of substance use prevention on cognitive functions generally, and executive functions and reward sensitivity specifically., Conclusion: This longitudinal, cluster-randomized controlled trial will investigate the impact of a brief personality-targeted intervention program on reducing the onset of addiction 4 years-post intervention. Results will tease apart the developmental sequences of uptake and growth in substance use and cognitive development in adolescence using developmentally sensitive neuropsychological measures., (© 2017 Society for the Study of Addiction.)

Background: No existing models of alcohol prevention concurrently adopt universal and selective approaches. This study aims to evaluate the first combined universal and selective approach to alcohol prevention., Method: A total of 26 Australian schools with 2190 students (mean age: 13.3 years) were randomized to receive: universal prevention (Climate Schools); selective prevention (Preventure); combined prevention (Climate Schools and Preventure; CAP); or health education as usual (control). Primary outcomes were alcohol use, binge drinking and alcohol-related harms at 6, 12 and 24 months., Results: Climate, Preventure and CAP students demonstrated significantly lower growth in their likelihood to drink and binge drink, relative to controls over 24 months. Preventure students displayed significantly lower growth in their likelihood to experience alcohol harms, relative to controls. While adolescents in both the CAP and Climate groups demonstrated slower growth in drinking compared with adolescents in the control group over the 2-year study period, CAP adolescents demonstrated faster growth in drinking compared with Climate adolescents., Conclusions: Findings support universal, selective and combined approaches to alcohol prevention. Particularly novel are the findings of no advantage of the combined approach over universal or selective prevention alone.

Background: Onset of alcohol use by 14 relative to 21 years of age strongly predicts elevated risk for severe alcohol use problems, with 27% versus 4% of individuals exhibiting alcohol dependence within 10 years of onset. What remains unclear is whether this early alcohol use (i) is a marker for later problems, reflected as a pre-existing developmental predisposition, (ii) causes global neural atrophy or (iii) specifically disturbs neuro-maturational processes implicated in addiction, such as executive functions or reward processing. Since our group has demonstrated that a novel intervention program targeting personality traits associated with adolescent alcohol use can prevent the uptake of drinking and binge drinking by 40 to 60%, a crucial question is whether prevention of early onset alcohol misuse will protect adolescent neurodevelopment and which domains of neurodevelopment can be protected., Methods: A subsample of 120 youth at high risk for substance misuse and 30 low-risk youth will be recruited from the Co-Venture trial (Montreal, Canada) to take part in this 5-year follow-up neuroimaging study. The Co-Venture trial is a community-based cluster-randomised trial evaluating the effectiveness of school-based personality-targeted interventions on substance use and cognitive outcomes involving approximately 3800 Grade 7 youths. Half of the 120 high-risk participants will have received the preventative intervention program. Cognitive tasks and structural and functional neuroimaging scans will be conducted at baseline, and at 24- and 48-month follow-up. Two functional paradigms will be used: the Stop-Signal Task to measure motor inhibitory control and a modified version of the Monetary Incentive Delay Task to evaluate reward processing., Discussion: The expected results should help identify biological vulnerability factors, and quantify the consequences of early alcohol abuse as well as the benefits of early intervention using brain metrics.

Aims: This study investigated the validity of a brief personality screening measure for substance use in adolescents, the Substance Use Risk Profile Scale (SURPS), among Australian adolescents., Design and Participants: A total of 527 adolescents (mean age: 13.38years, SD=0.43) from seven Australian schools were assessed at two time points 24months apart. The concurrent and predictive validity of the SURPS was determined using a series of linear and logistic regressions, and was compared to the results in a United Kingdom (UK) sample. SURPS subscale scores for the Australian population were also reported and compared to those in the UK., Findings: Overall, the SURPS subscale scores for Australian adolescents were similar to those for adolescents from the UK. Tests of concurrent and predictive validity in the Australian sample demonstrated that the all four personality profiles - Hopelessness (H), Anxiety Sensitivity (AS), Impulsivity (IMP), and Sensation Seeking (SS) - were related to measures of substance use and other behavioural and emotional characteristics. In addition, all the predicted specific prospective relationships between the personality profiles and particular substance use and other behavioural problems were confirmed except that H was not associated with illicit drug use. Overall, the results were similar between the Australian and UK samples., Conclusions: The SURPS is a valid and useful measure for identifying Australian adolescents at high-risk for substance use and other emotional and behavioural problems. Implications for prevention are discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Adolescence is a vulnerable time for both substance use and bullying involvement; however, there is limited research on substance use among adolescent victims of bullying. This study aimed to examine concurrent and prospective associations between bullying and substance use, differentiating between passive-victims, bully-victims and 'pure' bullies., Method: Associations between bullying involvement and substance use at baseline and 24 months post-baseline were examined in a cohort of adolescents in Australia. Bullying victims were divided into passive-victims (those who get bullied and do not bully others) and bully-victims (those who both get bullied and bully others). Perpetrators of bullying were divided into 'pure' bullies (those who bully others but do not get bullied), and bully-victims (as above). Outcomes examined were past six month use of alcohol (any drinking; risky drinking), tobacco, and cannabis., Results: While there was no evidence of an association between bullying victimization and/or perpetration and substance use at baseline, there was evidence of an association between bullying and substance use 24 months post-baseline. Specifically, there was evidence of increased odds of risky drinking and cannabis use for the bully-victim group., Conclusions: Bully-victim status at age 13 was associated with substance use at age 15, controlling for concurrent bullying involvement at age 15. Bully-victims are a particularly high-risk group that could benefit from targeted substance use preventive interventions. Reducing bullying is of great importance in reducing substance use and other harms among adolescents., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Changes in reward processing have been identified as one important pathogenetic mechanism in alcohol addiction. The nonsynonymous single nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene (rs6265/Val66Met) modulates the central nervous system activity of neurotransmitters involved in reward processing such as serotonin, dopamine, and glutamate. It was identified as crucial for alcohol consumption in healthy adults and, in rats, specifically related to the function in the striatum, a region that is commonly involved in reward processing. However, studies in humans on the association of BDNF Val66Met and reward-related brain functions and its role for alcohol consumption, a significant predictor of later alcohol addiction, are missing. Based on an intermediate phenotype approach, we assessed the early orientation toward alcohol and alcohol consumption in 530 healthy adolescents that underwent a monetary incentive delay task during functional magnetic resonance imaging. We found a significantly lower response in the putamen to reward anticipation in adolescent Met carriers with high versus low levels of alcohol consumption. During reward feedback, Met carriers with low putamen reactivity were significantly more likely to orient toward alcohol and to drink alcohol 2 years later. This study indicates a possible effect of BDNF Val66Met on alcohol addiction-related phenotypes in adolescence., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Longitudinal and family-based research suggests that conduct disorder, substance misuse, and ADHD involve both unique forms of dysfunction as well as more specific dysfunctions unique to each condition. Using direct measures of brain function, this study also found evidence in both unique and disorder-specific perturbations.

Genetic variation in a genomic region on chromosome 15q25.1, which encodes the alpha5, alpha3, and beta4 subunits of the cholinergic nicotinic receptor genes, confers risk to smoking and nicotine dependence (ND). Neural reward-related responses have previously been identified as important factors in the development of drug dependence involving ND. Applying an imaging genetics approach in two cohorts (N=487; N=478) of healthy non-smoking adolescents, we aimed to elucidate the impact of genome-wide significant smoking-associated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on reward-related neural responses in central regions such as the striatum, orbitofrontal and anterior cingulate cortex (ACC), and personality traits related to addiction. In both samples, carriers of the rs578776 GG compared with AG/AA genotype showed a significantly lower neural response to reward outcomes in the right ventral and dorsal ACC but not the striatum or the orbitofrontal cortex. Rs578776 was unrelated to neural reward anticipation or reward magnitude. Significantly higher scores of anxiety sensitivity in GG compared with AG/AA carriers were found only in sample 1. Associations with other personality traits were not observed. Our findings suggest that the rs578776 risk variant influences susceptibility to ND by dampening the response of the ACC to reward feedback, without recruiting the striatum or orbitofrontal cortex during feedback or anticipation. Thus, it seems to have a major role in the processing of and behavioral adaptation to changing reward outcomes.

Objective: The Substance Use Risk Profile Scale (SURPS) has been developed to screen personality risk factors for substance abuse. This scale assesses 4 high-risk personality traits using a 23-item, self-report questionnaire. SURPS helps guiding targeted approaches to prevention of substance abuse and misuse. It has been validated in the United Kingdom, English Canada, Sri Lanka, and China. This study aims to validate this scale in a sample of French-speaking adolescents from Quebec as well as its sensitivity in a clinical sample of adolescents., Method: Two hundred two 15-year-old youths from a community sample completed a French version of SURPS as well as other measures of personality and substance use. This study reports the internal consistency and concurrent validity of the scale, as well as a factor analysis of items. Further, 40 youths (mean age 15.7 years) from a clinical population completed SURPS and their scores were compared with those of the community sample., Results: SURPS French translation has good internal consistency and demonstrated a 4-factor structure very similar to the original scale. The 4 subscales show good concurrent validity, and 3 of the subscales were found to correlate with measures of substance use. Finally, 95% of the clinical sample was identified at high risk for substance misuse according to SURPS cut-off scores., Conclusion: SURPS French translation seems to be a valid and sensitive scale that can be used in a French-speaking adolescent population from Quebec.

Adolescence is a transition period that is assumed to be characterized by increased sensitivity to reward. While there is growing research on reward processing in adolescents, investigations into the engagement of brain regions under different reward-related conditions in one sample of healthy adolescents, especially in a target age group, are missing. We aimed to identify brain regions preferentially activated in a reaction time task (monetary incentive delay (MID) task) and a simple guessing task (SGT) in a sample of 14-year-old adolescents (N = 54) using two commonly used reward paradigms. Functional magnetic resonance imaging was employed during the MID with big versus small versus no win conditions and the SGT with big versus small win and big versus small loss conditions. Analyses focused on changes in blood oxygen level-dependent contrasts during reward and punishment processing in anticipation and feedback phases. We found clear magnitude-sensitive response in reward-related brain regions such as the ventral striatum during anticipation in the MID task, but not in the SGT. This was also true for reaction times. The feedback phase showed clear reward-related, but magnitude-independent, response patterns, for example in the anterior cingulate cortex, in both tasks. Our findings highlight neural and behavioral response patterns engaged in two different reward paradigms in one sample of 14-year-old healthy adolescents and might be important for reference in future studies investigating reward and punishment processing in a target age group.

Objective: To examine the long-term effects of a personality-targeted intervention on drinking quantity and frequency (QF), problem drinking, and personality-specific motivations for alcohol use in early adolescence., Method: A randomized control trial was carried out with 364 adolescents (median age 14) recruited from 13 secondary schools with elevated scores in Hopelessness, Anxiety-Sensitivity (AS), Impulsivity, and Sensation-Seeking. Participants were randomly assigned to a control no-intervention condition or a 2-session group coping skills intervention targeting 1 of 4 personality risk factors. The effects of the intervention on quantity/frequency (QF) of alcohol use, frequency of binge drinking, problem drinking, and motives were examined at 6, 12, 18, and 24 months postintervention., Results: Intent-to-treat repeated measures analyses revealed a significant overall intervention effect in reducing problem drinking symptoms, and a Time × Intervention effect on drinking QF and binge drinking frequency. Relative to the control group, the intervention group showed significantly reduced drinking and binge drinking levels at 6 months postintervention and reduced problem drinking symptoms for the full 24-month follow-up period (Cohen's d = 0.33). A significant Time × Intervention × Personality interaction was demonstrated for coping and enhancement drinking motives. In addition to an overall effect of intervention on coping motives, the AS group who received that intervention reported fewer coping motives compared with the AS control group at 12 and 24 months postintervention., Conclusions: This study provides further evidence showing that personality-targeted interventions reduce drinking behavior in adolescents in the short term. Novel findings were that the interventions were shown to produced long-term effects on drinking problems and personality-specific effects on drinking motives., ((PsycINFO Database Record (c) 2011 APA, all rights reserved).)

Background: Alcohol use motives are closely associated with specific profiles of alcohol use and reflect a subjectively derived decisional framework based on a motivational style of responding. Adult twin studies typically estimate the heritability of alcohol use motives to be between 7 and 42%, although relatively little is known about genetic and environmental influences upon alcohol use motives in adolescence., Methods: Latent class analysis (LCA) models containing 1 through 5 classes were fitted to the data derived from 1,422 adolescent twin and siblings self-reported alcohol use motives. Using twin models, we estimated the genetic, shared, and nonshared environmental influences to the class membership data derived from the LCA., Results: Four drinking motives classes were identified (family-oriented, social, enhancement/social, and coping/social). The coping/social and enhancement/social classes were differentiated from the social class on measures of depression, delinquency, and aggressive behavior. Analyses indicated that nonadditive genetic factors accounted for 76% of the variance in the coping/social motives class and additive genetic influences accounted for 66% of the variance in the social motives class. There was a moderate contribution of genetic factors and shared environmental factors influencing class membership of enhancement/social motivated drinkers (28 and 20% explained variance, respectively). Substantial shared environmental influences were revealed for membership of the family-oriented class (75%)., Conclusions: Heritable influences may predispose individuals to drink to cope with negative affect, for social reasons, and to a lesser extent for enhancement. Familial environmental influences shape family-oriented motives for drinking in adolescents., (Copyright © 2010 by the Research Society on Alcoholism.)

Sensation seeking, anxiety sensitivity, and hopelessness are personality risk factors for alcohol use disorders, each associated with specific risky drinking motives in adolescents. We developed a set of interventions and manuals that were designed to intervene at the level of personality risk and associated maladaptive coping strategies, including alcohol misuse. Manuals contained psychoeducational information on the target personality risk factor and how it is associated with maladaptive coping, as well as exercises targeting maladaptive cognitions and behaviors specific to each personality type. We tested the efficacy of these novel interventions on reducing drinking behavior by randomly assigning 297 Canadian high school students (56% girls, mean age 16, mean grade 11) to personality-targeted interventions (group format; 2 sessions) or to a no-treatment control group. Intent-to-treat analyses indicated beneficial effects of the intervention and Intervention x Personality interactions on drinking rates, drinking quantity, binge drinking, and problem drinking symptoms at 4-month follow-up.