Cannabis use in early adolescence: evidence of amygdala hypersensitivity to signals of threat

Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70) of 14-year olds with a history of cannabis use to a group (n = 70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood

Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use

The structure of psychopathology in adolescence and its common personality and cognitive correlates

The traditional view that mental disorders are distinct, categorical disorders has been challenged by evidence that disorders are highly comorbid and exist on a continuum (e.g., Caspi et al., 2014; Tackett et al., 2013). The first objective of this study was to use structural equation modeling to model the structure of psychopathology in an adolescent community-based sample (N = 2,144) including conduct disorder, attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), obsessive-compulsive disorder, eating disorders, substance use, anxiety, depression, phobias, and other emotional symptoms, assessed at 16 years. The second objective was to identify common personality and cognitive correlates of psychopathology, assessed at 14 years. Results showed that psychopathology at 16 years fit 2 bifactor models equally well: (a) a bifactor model, reflecting a general psychopathology factor, as well as specific externalizing (representing mainly substance misuse and low ADHD) and internalizing factors; and (b) a bifactor model with a general psychopathology factor and 3 specific externalizing (representing mainly ADHD and ODD), substance use and internalizing factors. The general psychopathology factor was related to high disinhibition/impulsivity, low agreeableness, high neuroticism and hopelessness, high delay-discounting, poor response inhibition and low performance IQ. Substance use was specifically related to high novelty-seeking, sensation-seeking, extraversion, high verbal IQ, and risk-taking. Internalizing psychopathology was specifically related to high neuroticism, hopelessness and anxiety-sensitivity, low novelty-seeking and extraversion, and an attentional bias toward negatively valenced verbal stimuli. Findings reveal several nonspecific or transdiagnostic personality and cognitive factors that may be targeted in new interventions to potentially prevent the development of multiple psychopathologies

Ventral striatum connectivity during reward anticipation in adolescent smokers

Substance misusers, including adolescent smokers, often have reduced reward system activity during processing of non-drug rewards. Using a psychophysiological interaction approach, we examined functional connectivity with the ventral striatum during reward anticipation in a large (N = 206) sample of adolescent smokers. Increased smoking frequency was associated with (1) increased connectivity with regions involved in saliency and valuation, including the orbitofrontal cortex and (2) reduced connectivity between the ventral striatum and regions associated with inhibition and risk aversion, including the right inferior frontal gyrus. These results demonstrate that functional connectivity during reward processing is relevant to adolescent addiction

Ventromedial prefrontal volume in adolescence predicts hyperactive/inattentive symptoms in adulthood

Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1,104 participants (M = 14.52 yrs, SD = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = -.274, p < .001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms

Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents.

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use

Peer victimization and its impact on adolescent brain development and psychopathology

Chronic peer victimization has long-term impacts on mental health; however, the biological mediators of this adverse relationship are unknown. We sought to determine whether adolescent brain development is involved in mediating the effect of peer victimization on psychopathology. We included participants (n = 682) from the longitudinal IMAGEN study with both peer victimization and neuroimaging data. Latent profile analysis identified groups of adolescents with different experiential patterns of victimization. We then associated the victimization trajectories and brain volume changes with depression, generalized anxiety, and hyperactivity symptoms at age 19. Repeated measures ANOVA revealed time-by victimization interactions on left putamen volume (F = 4.38, p = 0.037). Changes in left putamen volume were negatively associated with generalized anxiety (t = −2.32, p = 0.020). Notably, peer victimization was indirectly associated with generalized anxiety via decreases in putamen volume (95% CI = 0.004–0.109). This was also true for the left caudate (95% CI = 0.002–0.099). These data suggest that the experience of chronic peer victimization during adolescence might induce psychopathology-relevant deviations from normative brain development. Early peer victimization interventions could prevent such pathological changes