Neurocognitive consequences of adolescent sleep disruptions and their relationship to psychosis vulnerability: a longitudinal cohort study.

Adolescence is a key period for neurocognitive maturation where deviation from normal developmental trajectories may be tied to adverse mental health outcomes. Cognitive disruptions have been noted in populations at risk for psychosis and are known to accompany periods of sleep deprivation. This study aims to assess the role of cognition as a mediator between sleep disruptions and psychosis risk. A cohort of 3801 high school students (51% female, mean age = 12.8, SD = 0.45 years) was recruited from 31 Montreal high schools. Measures of sleep, psychotic-like experiences, inhibition, working memory, perceptual reasoning, and delayed recall were collected from participants on a yearly basis over the five years of their high school education. A multi-level model mediation analysis was performed controlling for sex and time squared. Response inhibition was shown to be associated with, and to mediate (B = -0.005, SD = 0.003, p = 0.005*) the relationship between sleep disruptions (B = -0.011, SD = 0.004, p < 0.001*) and psychotic-like experiences (B = 0.411, SD = 0.170, p = 0.005*). Spatial working memory deficits on a given year were associated with a higher frequency of psychotic-like experiences that same year (B = -0.046, SD = 0.018, p = 0.005*) and the following year (B = -0.051, SD = 0.023, p = 0.010*), but were not associated with sleep disturbances. No significant associations were found between our variables of interest and either delayed recall or perceptual reasoning at the within person level. Findings from this large longitudinal study provide evidence that the association between sleep disruptions and psychosis risk is specifically mediated by inhibitory rather than general cognitive impairments. The association of spatial working memory, response inhibition, and sleep disruptions with psychotic-like experiences suggests that these factors may represent potential targets for preventative interventions.

The long-term effectiveness of a personality-targeted substance use prevention program on aggression from adolescence to early adulthood.

BACKGROUND: Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20. METHODS: In total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12-15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering. RESULTS: Across the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = -0.42; 95% confidence interval [CI] -0.64 to -0.20; p < 0.001), reactive aggression (b = -0.22; 95% CI 0.35 to -0.10; p = 0.001), and proactive aggression (b = -0.14; 95% CI -0.23 to -0.05; p = 0.002) was greater for the Preventure group compared to the control group. CONCLUSIONS: The study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

Effect of a selective personality-targeted prevention program on 7-year illicit substance related outcomes: A secondary analysis of a cluster randomized controlled trial.

BACKGROUND: This study evaluated the efficacy of the selective personality-targeted PreVenture program in reducing cannabis and stimulant use over a 7-year period spanning adolescence and early adulthood. METHODS: A cluster randomized controlled trial was conducted in 14 Australian schools. Schools were randomized to PreVenture, a brief personality-targeted selective intervention, comprising two 90-minute facilitator-led sessions delivered one week apart, or a control group (health education as usual). Only students who scored highly on one of four personality traits (anxiety sensitivity, negative thinking, impulsivity, sensation seeking) were included. Students completed online self-report questionnaires between 2012 and 2019: at baseline; post-intervention; 1-, 2-, 3-, 5.5- and 7-years post-baseline. Outcomes were past 6-months cannabis use, stimulant use (MDMA, methamphetamine or amphetamine) and cannabis-related harms. RESULTS: The sample comprised 438 adolescents (Mage=13.4 years; SD=0.47) at baseline. Retention ranged from 51% to 79% over the 7-years. Compared to controls, the PreVenture group had significantly reduced odds of annual cannabis-related harms (OR=0.78, 95% CI=0.65-0.92). However, there were no significant group differences in the growth of cannabis use (OR=0.84, 95% CI=0.69-1.02) or stimulant use (OR=1.07, 95% CI=0.91-1.25) over the 7-year period. CONCLUSIONS: PreVenture was effective in slowing the growth of cannabis-related harms over time, however owing to missing data over the 7-year trial, replication trials may be warranted to better understand the impact of the PreVenture intervention on cannabis and stimulant use among young Australians. Alternative implementation strategies, such as delivering the intervention in later adolescence and/or providing booster sessions, may be beneficial.

High peak drinking levels mediate the relation between impulsive personality and injury risk in emerging adults.

BACKGROUND: Alcohol-induced injury is one of the leading causes of preventable morbidity and mortality. We investigated the relationship between impulsive personality and physical injury (e.g. falls, sports), and whether peak drinking quantity specifically, and/or risky behaviour more generally, mediates the relationship between impulsivity and injury in undergraduates. METHOD: We used data from the winter 2021 UniVenture survey with 1316 first- and second-year undergraduate students aged 18-25 years (79.5% female) from five Canadian Universities. Students completed an online survey regarding their demographics, personality, alcohol use, risky behaviours, and injury experiences. Impulsivity was measured with the substance use risk profile scale, past 30-day peak alcohol use with the quantity-frequency-peak Alcohol Use Index, general risky behaviour with the risky behaviour questionnaire, and past 6-month injury experience with the World Health Organization's (2017) injury measurement questionnaire. RESULTS: Of 1316 total participants, 12.9% (n = 170) reported having sustained a physical injury in the past 6 months. Mean impulsivity, peak drinking quantity, and risky behaviour scores were significantly higher among those who reported vs. did not report injury. Impulsivity and peak drinking quantity, but not general risky behaviour, predicted injury in a multi-level generalized mixed model. Mediation analyses supported impulsivity as both a direct predictor of physical injury and an indirect predictor through increased peak drinking (both p < .05), but not through general risky behaviour. CONCLUSION: Results imply emerging adults with impulsive tendencies should be identified for selective injury prevention programs and suggest targeting their heavy drinking to decrease their risk for physical injury.

Neuroscience-informed classification of prevention interventions in substance use disorders: An RDoC-based approach.

Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to create more effective interventions for SUD treatment and prevention. Recent large-scale cohort studies from early childhood are generating multiple levels of neuroscience-based information with the potential to inform the development and refinement of future preventive strategies. However, there are still no available well-recognized frameworks to guide the integration of these multi-level datasets into prevention interventions. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioral domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science and adapted the framework for the existing preventive interventions. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents, we identified 22 unique preventive interventions. By teasing apart these 22 interventions into the RDoC domains, we proposed distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, to be targeted, engaged and modified for effective addiction prevention.

Brain structural covariance network features are robust markers of early heavy alcohol use.

BACKGROUND AND AIMS: Recently, we demonstrated that a distinct pattern of structural covariance networks (SCN) from magnetic resonance imaging (MRI)-derived measurements of brain cortical thickness characterized young adults with alcohol use disorder (AUD) and predicted current and future problematic drinking in adolescents relative to controls. Here, we establish the robustness and value of SCN for identifying heavy alcohol users in three additional independent studies. DESIGN AND SETTING: Cross-sectional and longitudinal studies using data from the Pediatric Imaging, Neurocognition and Genetics (PING) study (n = 400, age range = 14-22 years), the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) (n = 272, age range = 17-22 years) and the Human Connectome Project (HCP) (n = 375, age range = 22-37 years). CASES: Cases were defined based on heavy alcohol use patterns or former alcohol use disorder (AUD) diagnoses: 50, 68 and 61 cases were identified. Controls had none or low alcohol use or absence of AUD: 350, 204 and 314 controls were selected. MEASUREMENTS: Graph theory metrics of segregation and integration were used to summarize SCN. FINDINGS: Mirroring our prior findings, and across the three data sets, cases had a lower clustering coefficient [area under the curve (AUC) = -0.029, P = 0.002], lower modularity (AUC = -0.14, P = 0.004), lower average shortest path length (AUC = -0.078, P = 0.017) and higher global efficiency (AUC = 0.007, P = 0.010). Local efficiency differences were marginal (AUC = -0.017, P = 0.052). That is, cases exhibited lower network segregation and higher integration, suggesting that adjacent nodes (i.e. brain regions) were less similar in thickness whereas spatially distant nodes were more similar. CONCLUSION: Structural covariance network (SCN) differences in the brain appear to constitute an early marker of heavy alcohol use in three new data sets and, more generally, demonstrate the utility of SCN-derived metrics to detect brain-related psychopathology.

Do anxiety symptoms and coping motives serially mediate the association between psychotic-like experiences and cannabis-related problems in undergraduate recent cannabis users?

Many Canadian emerging adults (ages 18-25 years) use cannabis, with 60 % of past-three-month users experiencing one or more cannabis-related problems (i.e., adverse consequences of use). While psychotic-like experiences (PLEs) and cannabis problems overlap, little is known about the mechanisms explaining this link. One hypothesis is that PLEs are distressing and give rise to anxiety, with which emerging adults attempt to cope through increased cannabis use, in turn increasing their risk for cannabis-related problems. We tested a chained-mediational model to determine if anxiety and coping-with-anxiety motives for cannabis use sequentially mediated the link between PLEs and cannabis problems in emerging adult undergraduates; a conditional process model tested for moderation by sex. Emerging adult cannabis users (N = 413; mean [SD] age = 19.1 [1.5] years; 71.9 % female) from five Canadian universities provided cross-sectional, self-report survey data in fall 2021. Validated measures of PLEs, anxiety, cannabis coping-with-anxiety motives, and cannabis-related problems were administered. Path analyses supported the hypothesized chained mediational indirect effect (b = 0.027, 95 % bootstrap CI [0.012, 0.050]). No direct effect was found (p =.698), suggesting that the PLEs-to-cannabis problems association is fully explained by anxiety and cannabis coping-with-anxiety motives. Inconsistent with hypotheses, mediation did not depend on sex (95 % CIs crossed zero); therefore, anxiety and cannabis coping-with-anxiety motives explain the link between PLEs and cannabis problems in emerging adults regardless of their sex. Results highlight anxiety and cannabis coping-with-anxiety motives as potentially important intervention targets in cannabis-using emerging adults with PLEs, possibly preventing the development/worsening of cannabis-related problems.

Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization.

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins, and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3,000 study participants. The model and scripts described here are freely available through CentileBrain (https://centilebrain.org/).

Screen time, impulsivity, neuropsychological functions and their relationship to growth in adolescent attention-deficit/hyperactivity disorder symptoms.

Previous longitudinal studies found significant associations between screen time and increase in attention-deficit/hyperactivity disorder (ADHD) symptoms, but the mechanisms mediating this association remain understudied. Thus, we used data from a 5-year population-based longitudinal cohort of nearly 4000 Canadian high school students, modeled using multivariate multilevel mediation, to investigate the association of screen time (i.e., social media, television, video games, computer use) with ADHD symptoms via different potential behavioral and neuropsychological mediators (i.e. impulsivity, response inhibition, working memory). We studied direct and indirect between-person, concurrent within-person, and lagged-within-person effects of screens on ADHD symptoms. Results showed that increases in screen time in a given year were associated with an exacerbation of ADHD symptoms within that same year (within-person association), over and above potential common vulnerability (between-person association). Impulsivity proved to be the most robust mediator in the association of screen time with ADHD symptoms at both between and within-person levels. Only social media use displayed a significant lagged-within-person association with ADHD symptoms mediated by impulsivity, indicating an enduring influence on behavior, which was further shown to be mediated by chained changes in response inhibition on a Go/No-Go task. These findings provide clinical implications of screen time and should be an important focus in the management and prevention of ADHD symptoms among adolescents.

Brain volumes in alcohol use disorder: Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis.

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.

Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: testing gene × environment moderation and mediation.

BACKGROUND: It has not yet been determined if the commonly reported cannabis-psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders. METHODS: We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort. RESULTS: PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects. CONCLUSIONS: These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis-psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

The four-factor personality model and its qualitative correlates among opioid agonist therapy clients.

Background: The Four Factor Personality Vulnerability model identifies four specific personality traits (e.g., sensation seeking [SS], impulsivity [IMP], anxiety sensitivity [AS], and hopelessness [HOP]) as implicated in substance use behaviors, motives for substance use, and co-occurring psychiatric conditions. Although the relationship between these traits and polysubstance use in opioid agonist therapy (OAT) clients has been investigated quantitatively, no study has examined the qualitative expression of each trait using clients' voice. Method: Nineteen Methadone Maintenance Therapy (MMT) clients (68.4% male, 84.2% white, mean age[SD] = 42.71 [10.18]) scoring high on one of the four personality traits measured by the Substance Use Risk Profile Scale [SURPS] completed a semi-structured qualitative interview designed to explore their lived experience of their respective trait. Thematic analysis was used to derive themes, which were further quantified using content analysis. Results: Themes emerging from interviews reflected (1) internalizing and externalizing symptoms, (2) adversity experiences, and (3) polysubstance use. Internalizing symptoms subthemes included symptoms of anxiety, fear, stress, depression, and avoidance coping. Externalizing subthemes included anger, disinhibited cognitions, and anti-social and risk-taking behaviors. Adverse experiences subthemes included poor health, poverty, homelessness, unemployment, trauma, and conflict. Finally, polysubstance use subthemes include substance types, methods of use, and motives. Differences emerged between personality profiles in the relative endorsement of various subthemes, including those pertaining to polysubstance use, that were largely as theoretically expected. Conclusion: Personality is associated with unique cognitive, affective, and behavioral lived experiences, suggesting that personality may be a novel intervention target in adjunctive psychosocial treatment for those undergoing OAT.

The 3-year effects of a personality-targeted prevention program on general and specific dimensions of psychopathology.

This study aimed to examine the effect of a personality-targeted prevention program (Preventure) on trajectories of general and specific dimensions of psychopathology from early- to mid-adolescence. Australian adolescents (N = 2190) from 26 schools participated in a cluster randomized controlled substance use prevention trial. This study compared schools allocated to deliver Preventure (n = 13 schools; n = 466 students; Mage = 13.42 years), a personality-targeted selective intervention, with a control group (n = 7 schools; n = 235 students, Mage = 13.47 years). All participants were assessed for psychopathology symptoms at baseline, 6-, 12-, 24- and 36-months post-baseline. Outcomes were a general psychopathology factor and four specific factors: fear, distress, alcohol use/harms and conduct/inattention), extracted from a higher-order model. Participants who screened as 'high-risk' on at least one of four personality traits (negative thinking, anxiety sensitivity, impulsivity and sensation seeking) were included in intention-to-treat analyses. Intervention effects were examined using multi-level mixed models accounting for school-level clustering. Among high-risk adolescents, growth in general psychopathology was slower in the Preventure group compared to the control group (b = -0.07, p = 0.038) across the three years. After controlling for effects on general psychopathology, there were no significant, additional effects on the lower order factors. This study provides evidence for the effectiveness of a selective personality-targeted intervention in altering trajectories of general psychopathology during adolescence. This finding represents impacts on multiple symptom domains and highlights the potential for general psychopathology as an intervention target.

Differential associations of adolescent versus young adult cannabis initiation with longitudinal brain change and behavior.

Leveraging ~10 years of prospective longitudinal data on 704 participants, we examined the effects of adolescent versus young adult cannabis initiation on MRI-assessed cortical thickness development and behavior. Data were obtained from the IMAGEN study conducted across eight European sites. We identified IMAGEN participants who reported being cannabis-naïve at baseline and had data available at baseline, 5-year, and 9-year follow-up visits. Cannabis use was assessed with the European School Survey Project on Alcohol and Drugs. T1-weighted MR images were processed through the CIVET pipeline. Cannabis initiation occurring during adolescence (14-19 years) and young adulthood (19-22 years) was associated with differing patterns of longitudinal cortical thickness change. Associations between adolescent cannabis initiation and cortical thickness change were observed primarily in dorso- and ventrolateral portions of the prefrontal cortex. In contrast, cannabis initiation occurring between 19 and 22 years of age was associated with thickness change in temporal and cortical midline areas. Follow-up analysis revealed that longitudinal brain change related to adolescent initiation persisted into young adulthood and partially mediated the association between adolescent cannabis use and past-month cocaine, ecstasy, and cannabis use at age 22. Extent of cannabis initiation during young adulthood (from 19 to 22 years) had an indirect effect on psychotic symptoms at age 22 through thickness change in temporal areas. Results suggest that developmental timing of cannabis exposure may have a marked effect on neuroanatomical correlates of cannabis use as well as associated behavioral sequelae. Critically, this work provides a foundation for neurodevelopmentally informed models of cannabis exposure in humans.

Do Anxiety Symptoms Mediate the Association Between Cannabis Use Frequency and Psychotic-Like Experiences in Emerging Adult Undergraduates?

OBJECTIVE: Cannabis is commonly used by Canadian emerging adults (ages 18-25 years), many of whom attend post-secondary institutions. Frequent cannabis use is linked with psychotic-like experiences (PLEs); however, the exact nature of this association remains unclear. Anxiety symptoms may mediate this association, as they are prevalent in emerging adults and have been independently linked with both cannabis use and PLEs. Past work found that anxiety mediated the association between cannabis use frequency and attenuated positive psychotic symptoms (further along the psychosis continuum than PLEs), however this research had yet to be validated in the Canadian population, and trait rather than state anxiety (frequency of anxiety symptoms) was studied. Thus, our primary objective was to examine if anxiety symptoms mediated the association between cannabis use frequency and PLEs in Canadian emerging adult undergraduates. Despite known sex differences in cannabis use, expression of anxiety, and PLEs, past work did not evaluate the potential impact of biological sex on the anxiety-mediated model, and thus is the secondary objective of the present study. METHODS: 1,266 first-/second-year emerging adult undergraduates from five Canadian universities provided cross-sectional, self-report survey data in fall 2021 semester. Validated measures of cannabis use frequency, anxiety, and PLEs were administered. RESULTS: Path analyses supported mediation from cannabis use to PLEs through anxiety (b = 0.07, P < 0.001, 95% bootstrap CI [0.03, 0.10]). No direct effect was found (P = 0.457), suggesting that the cannabis-to-PLEs association was mediated by anxiety. Mediation did not depend on biological sex (i.e., bootstrapped 95% CIs crossed zero). CONCLUSIONS: Anxiety symptoms mediated the association between cannabis use and PLEs in emerging adults regardless of their biological sex. Assuming replication in prospective research, results highlight anxiety as an important intervention target in frequent cannabis-using emerging adults, to potentially prevent development/worsening of PLEs, and in turn psychotic illness.

A longitudinal mediation study of peer victimization and resting-state functional connectivity as predictors of development of adolescent psychopathology.

Background: Peer victimization (PV) is associated with alterations in neural responses in regions subserving emotional regulatory processes and with increased risk of psychopathology during adolescence. The present study examined the longitudinal mediating effects of resting-state functional connectivity (rsFC) between adolescent PV and subsequent internalizing (depression and anxiety), and externalizing (conduct and hyperactivity/inattention) symptoms. Methods: 151 adolescents (baseline mean age 12-14; 54% males) were assessed and imaged three times during a five-year period. We focused on rsFC of a priori determined Regions-of-Interest (ROIs) guided by the literature (i.e., amygdala, anterior and posterior insula, anterior cingulate cortex, and medial prefrontal cortex). Multilevel mediation (MLM) analyses simultaneously examined the between-person, concurrent within-person, and lagged within-person associations between PV and internalizing/externalizing symptoms through changes in couplings of the amygdala with the other four ROIs. All models controlled for the effects of self-reported childhood maltreatment and sex differences. Results: An increased rsFC of the amygdala-posterior insula significantly mediated the lagged within-person association of PV and internalizing symptoms (ß = 0.144; 95% CI [0.018, 0.332]). This effect was significant regardless of childhood maltreatment, concurrent externalizing symptoms, and sex differences. The rsFC did not mediate the relationship between PV and externalizing symptoms. Conclusions: Results of this study suggest that adolescent PV may lead to long-lasting maladaptive neural communication between emotional response and sensory perception of pain (i.e., bottom-up emotion regulation) and that these neural responses may serve as unique markers for increased internalizing symptoms that appear in later adolescence in peer-victimized youth. These findings have implications for interventions targeting internalizing symptoms in victimized adolescents.

Sleep as a Mediator Between Cannabis Use and Psychosis Vulnerability: A Longitudinal Cohort Study.

Objectives: Increasing evidence implicates cannabis consumption as a key risk factor in the development of psychosis, but the mechanisms underpinning this relationship remain understudied. This study proposes to determine whether sleep disruption acts as a mediator of the cannabis-to-psychosis relationship. Study Design: This longitudinal study assessed measures of cannabis use frequency, sleep quality (SQ), and psychotic-like experiences (PLEs) were collected using self-reported questionnaires. Data were collected from September 2012 to September 2018. Data were collected from a general population sample of adolescents who entered the seventh grade in 31 schools in the Greater Montreal area. The study uses data collected on an annual basis from 3801 high school students from grades 7 to 11. The aforementioned measures were measured using the Detection of Alcohol and Drug Problems in Adolescents questionnaire, a SQ Likert scale, and measures the Psychotic-Like Experiences Questionnaire for Children. Study Results: Results show a reciprocal 1-year cross-lagged effect of cannabis use and sleep (ß = -0.076, 95% CI = -0.037 to -0.018, P = .000), of sleep on cannabis use (ß = -.016, 95% CI = -0.025 to -0.006, P = .007), of sleep on PLEs (ß = -0.077, 95%CI = -0.014 to -0.051, P = .000), and of PLEs on sleep (ß = -0.027, 95% CI = -0.037 to -0.018, P = .000). We additionally found a 2 years indirect lagged-effect of cannabis use on PLEs (ß = 0.068, 95% CI = 0.024 to 0.113, P = .011) mediated by 1-year sleep (ß = 0.006, 95% CI = 0.003 to 0.009, P = .001). Conclusions: Our results suggest sleep disruptions simultaneously aggravate, and are aggravated by, cannabis addiction and PLEs. The longitudinal sleep-mediated effect of cannabis use on PLEs encourages further research into the role of sleep as a potential therapeutic target in the prevention of cannabis-related psychosis.

Longitudinal associations between adolescent catch-up sleep, white-matter maturation and internalizing problems.

Sleep is an important contributor for neural maturation and emotion regulation during adolescence, with long-term effects on a range of white matter tracts implicated in affective processing in at-risk populations. We investigated the effects of adolescent sleep patterns on longitudinal changes in white matter development and whether this is related to the emergence of emotional (internalizing) problems. Sleep patterns and internalizing problems were assessed using self-report questionnaires in adolescents recruited in the general population followed up from age 14-19 years (N = 111 White matter structure was measured using diffusion tensor imaging (DTI) and estimated using fractional anisotropy (FA). We found that longitudinal increases in time in bed (TIB) on weekends and increases in TIB-variability between weekdays to weekend, were associated with an increase in FA in various interhemispheric and cortico-striatal tracts. Extracted FA values from left superior longitudinal fasciculus mediated the relationship between increases in TIB on weekends and a decrease in internalizing problems. These results imply that while insufficient sleep might have potentially harmful effects on long-term white matter development and internalizing problems, longer sleep duration on weekends (catch-up sleep) might be a natural counteractive and protective strategy.

Inhibited personality traits, internalizing symptoms, and drinking to cope during the COVID-19 pandemic among emerging adults.

Emerging adults with high levels of inhibited personality traits may be at-risk for drinking to cope during the COVID-19 pandemic. The current research explored mediational pathways between two inhibited personality traits (anxiety sensitivity (AS) and hopelessness (HOP)), internalizing symptoms (anxiety, depression, and COVID-19 distress), and coping drinking motives (drinking to cope with anxiety and drinking to cope with depression) during the pandemic. Cross-sectional data were collected from 879 undergraduate drinkers (79% female, 83% White, 18-25 years old) at five Canadian universities from January-April 2021. Participants self-reported on their personality, anxiety (GAD-7), depressive symptoms (PHQ-9), COVID-19 distress, and coping drinking motives. Mediational path analyses provided evidence of both specific and non-specific pathways between personality and coping motives via internalizing symptoms. Depressive symptoms partially mediated the link between HOP and drinking to cope with depression motives. While anxiety symptoms did not significantly mediate links between AS and coping with anxiety motives in the full model, evidence of mediation was found in a post-hoc sensitivity analysis. COVID-19 distress served as a non-specific mediator. AS and HOP are critical transdiagnostic risk factors that increase vulnerability for internalizing psychopathology and, in turn, risky drinking motives, in the context of the COVID-19 pandemic.