The relationship between brain structure and general psychopathology in preadolescents.

BACKGROUND: An emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging. METHODS: This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,875; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. RESULTS: Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents. CONCLUSIONS: The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.

Neuroscience literacy and substance use prevention: How well do young people understand their brain?

ISSUE: Reducing substance use harm in young people is a major public health priority, however, health promotion messages often struggle to achieve meaningful engagement. Neuroscience-based teachings may provide an innovative new way to engage young people in credible harm minimisation health promotion. This study aims to evaluate the acceptability and credibility of a series of neuroscience-based drug education animations and investigate neuroscience literacy in young people. METHODS: Three animations were developed around the impact of alcohol, MDMA and cannabis use on the growing brain, labelled the 'Respect Your Brain' video series. Sixty young people (mean age 21.9 years; 48% female) viewed the animations and completed a 20-minute web-based, self-report survey to provide feedback on the animations and a 19-item neuroscience literacy survey, assessing knowledge and attitudes towards the brain. RESULTS: The Alcohol, Cannabis and MDMA videos were rated as good or very good by the majority of participants (82%, 89% and 85%, respectively) and all participants wanted to see more 'Respect your Brain' videos. On average the Alcohol, Cannabis and MDMA videos were rated as containing the right level of detail and being interesting, relevant and engaging by the majority of participants (80%, 81% and 83%, respectively). Participants scored an average of 74% in the neuroscience literacy questionnaire, demonstrating some knowledge of brain functioning and positive attitudes towards the brain. CONCLUSION: This study provides evidence that age-appropriate, neuroscience-based resources on alcohol, Cannabis and MDMA are engaging and relevant to young people and offer a potential new avenue to reduce alcohol and other drug related harm and promote healthy lifestyle choices in young people.

Fetal alcohol spectrum disorder resources for educators: A scoping review.

Children with foetal alcohol spectrum disorder (FASD) can experience neurodevelopmental, physical, psychological and behavioural impairments that can result in a disrupted school experience. However, educators often have limited knowledge or experience in the identification and support of students with FASD, and there is a critical need for effective tools and resources to ensure students with FASD are supported in their ongoing learning and development. This scoping review aimed to identify and evaluate publicly available educator resources that aid in the identification, and support of students with FASD in primary/elementary school. In addition, educators and FASD experts were consulted to obtain feedback on currently available resources, and key issues and priorities for FASD resources. In total, 124 resources were identified by searching peer-reviewed and grey literature databases, app stores, podcast services and contacting FASD experts. Information was found on identification (23 resources) and support of students with FASD (119 resources). No resources provided information on the referral. Most resources were average (40%) to good (33%) quality, as measured by a composite tool based on adaptions of the NHMRC FORM Framework and iCAHE Guideline Quality Checklist. A minority of resources had been formally evaluated (7%). Review findings and consultations with experts and educators indicate a critical need for referral guides, evidence-based short-format resources and centralised access for school communities to high-quality resources. Taken together, this study has identified key areas for future resource development and research to better support primary school students with FASD.

Parental Family History of Alcohol Use Disorder and Neural Correlates of Response Inhibition in Children From the Adolescent Brain Cognitive Development (ABCD) Study.

BACKGROUND: Youth whose parents have alcohol use disorder (AUD) are at higher risk for earlier initiation and greater magnitude of alcohol use, and have a higher likelihood of developing an AUD than their peers without parental history of AUD. This increased risk may be partly attributable to altered development of inhibitory control and related neural circuitry. This study examined neural activation during a motor response inhibition Stop Signal Task (SST) in substance-naïve youth aged 9 to 10 years with and without parental family history of AUD. METHODS: Baseline cross-sectional survey and functional magnetic resonance imaging (fMRI) data were drawn from 6,898 youth in the US-based Adolescent Brain Cognitive Development Study. Generalized additive mixed models were conducted to examine the association between maternal, paternal, and parental (both mother and father) family history of AUD with neural activation during successful and failed response inhibition. Family history interactions with sex and stratification by ethnicity were explored. RESULTS: Of 6,898 participants, 951 (14%) were family history positive for any parental AUD. Paternal history of AUD was associated with greater activation for successful inhibition in the right medial orbital frontal gyrus, compared to youth with no family history. Maternal history of AUD was associated with greater activation for failed response inhibition among females in the cerebellum, compared to females with no such history. Parental history (both mother and father) of AUD was associated with greater activation during successful inhibition in the left paracentral gyri and left superior parietal lobule. Maternal history and parental history of AUD findings were accounted for by a family history of substance use disorder in general. All effect sizes were relatively small. CONCLUSIONS: Substance-naïve children with a parental family history of AUD exhibit greater neural activation in some regions of the fronto-basal ganglia and cerebellar networks when they successfully or unsuccessfully inhibit a response as compared to children with no such family history. This unique neural response pattern could reflect a compensatory response and may represent an inherent neurobiological vulnerability to risk-related behaviors in these youth which will be examined in future longitudinal analyses of this cohort.

Screen media activity does not displace other recreational activities among 9-10 year-old youth: a cross-sectional ABCD study®.

BACKGROUND: Screen media is among the most common recreational activities engaged in by children. The displacement hypothesis predicts that increased time spent on screen media activity (SMA) may be at the expense of engagement with other recreational activities, such as sport, music, and art. This study examined associations between non-educational SMA and recreational activity endorsement in 9-10-year-olds, when accounting for other individual (i.e., cognition, psychopathology), interpersonal (i.e., social environment), and sociodemographic characteristics. METHODS: Participants were 9254 youth from the Adolescent Brain Cognitive Development Study®. Latent factors reflecting SMA, cognition, psychopathology, and social environment were entered as independent variables into logistic mixed models. Sociodemographic covariates included age, sex, race/ethnicity, education, marital status, and household income. Outcome variables included any recreational activity endorsement (of 19 assessed), and specific sport (swimming, soccer, baseball) and hobby (music, art) endorsements. RESULTS: In unadjusted groupwise comparisons, youth who spent more time engaging with SMA were less likely to engage with other recreational activities (ps < .001). However, when variance in cognition, psychopathology, social environment, and sociodemographic covariates were accounted for, most forms of SMA were no longer significantly associated with recreational activity engagement (p > .05). Some marginal effects were observed: for every one SD increase in time spent on games and movies over more social forms of media, youth were at lower odds of engaging in recreational activities (adjusted odds ratio = 0·83, 95% CI 0·76-0·89). Likewise, greater general SMA was associated with lower odds of endorsing group-based sports, including soccer (0·93, 0·88-0·98) and baseball (0·92, 0·86-0·98). Model fit comparisons indicated that sociodemographic characteristics, particularly socio-economic status, explained more variance in rates of recreational activity engagement than SMA and other latent factors. Notably, youth from higher socio-economic families were up to 5·63 (3·83-8·29) times more likely to engage in recreational activities than youth from lower socio-economic backgrounds. CONCLUSIONS: Results did not suggest that SMA largely displaces engagement in other recreational activities among 9-10-year-olds. Instead, socio-economic factors greatly contribute to rates of engagement. These findings are important considering recent shifts in time spent on SMA in childhood.

Preventing Substance Use Among Indigenous Adolescents in the USA, Canada, Australia and New Zealand: a Systematic Review of the Literature.

This systematic review assessed the current evidence base of substance use prevention programs for Indigenous adolescents in the USA, Canada, Australia and New Zealand. The authors investigated (a) the outcomes, type, setting and context of prevention programs; (b) the common components of beneficial prevention programs; and (c) the methodological quality of evaluations of included prevention programs. The authors searched eight peer-reviewed and 20 grey literature databases for studies published between 1 January 1990 and 31 August 2017. Data extracted included type of program (culturally adapted, culture-based or unadapted), the setting (school, community, family or multi-setting), delivery (computerised or traditional), context (Indigenous-specific or multi-cultural environment) and common components of the programs. Program evaluation methodologies were critically appraised against standardised criteria. This review identified 26 eligible studies. Substance use prevention programs for Indigenous youth led to reductions in substance use frequency and intention to use; improvements in substance-related knowledge, attitudes and resistance strategies; and delay in substance use initiation. Key elements of beneficial programs included substance use education, skills development, cultural knowledge enhancement and community involvement in program development. Five programs were rated as methodologically strong, seven were moderate and fourteen were weak. Prevention programs have the potential to reduce substance use among Indigenous adolescents, especially when they are developed in partnership with Indigenous people. However, more rigorously conducted evaluation trials are required to strengthen the evidence base.

Neurobiological and Cognitive Profile of Young Binge Drinkers: a Systematic Review and Meta-Analysis.

This review provides the first systematic and quantitative synthesis of the literature examining the relationship between binge drinking, cognition, brain structure and function in youth aged 10 to 24 years. PubMed, EMBASE, Medline, PsychINFO and ProQuest were searched for neuroimaging, neurophysiological, and neuropsychological studies. A total of 58 studies (21 neuroimaging, 16 neurophysiological, 21 neuropsychological) met the eligibility criteria and were included in the review. Overall, abnormal or delayed development of key frontal executive-control regions may predispose youth to binge drink. These abnormalities appear to be further exacerbated by the uptake of binge drinking, in addition to alcohol-related neural aberrations in reward-seeking and incentive salience regions, indexed by cognitive deficits and maladaptive alcohol associations. A meta-analysis of neuropsychological correlates identified that binge drinking in youth was associated with a small overall neurocognitive deficit (g = -0.26) and specific deficits in decision-making (g = -1.70), and inhibition (g = -0.39). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) Evidence Profile, the certainty in outcomes ranged from very low to low. Future prospective longitudinal studies should address concomitant factors, exposure thresholds, and age-related vulnerabilities of binge drinking, as well as the degree of recovery following discontinuation of use.

Alcohol and Cannabis Use and the Developing Brain.

PURPOSE: Alcohol and cannabis are the most commonly used substances during adolescence and are typically initiated during this sensitive neurodevelopmental period. The aim of this review is to provide a comprehensive overview of the most recent literature focused on understanding how these substances affect the developing brain. SEARCH METHODS: Articles included in this review were identified by entering 30 search terms focused on substance use, adolescence, and neurodevelopment into MEDLINE, Embase, PsycINFO, ProQuest Central, and Web of Science. Studies were eligible for inclusion if they longitudinally examined the effect of adolescent alcohol and/or cannabis use on structural or functional outcomes in 50 or more participants. SEARCH RESULTS: More than 700 articles were captured by the search, and 43 longitudinal studies met inclusion criteria, including 18 studies focused on alcohol use, 13 on cannabis use, and 12 on alcohol and cannabis co-use. DISCUSSION AND CONCLUSIONS: Existing studies suggest heavy alcohol and cannabis use during adolescence are related to small to moderate disruptions in brain structure and function, as well as neurocognitive impairment. The effects of alcohol use include widespread decreases in gray matter volume and cortical thickness across time; slowed white matter growth and poorer integrity; disrupted network efficiency; and poorer impulse and attentional control, learning, memory, visuospatial processing, and psychomotor speed. The severity of some effects is dependent on dose. Heavy to very heavy cannabis use is associated with decreased subcortical volume and increased frontoparietal cortical thickness, disrupted functional development, and decreased executive functioning and IQ compared to non-using controls. Overall, co-use findings suggest more pronounced effects related to alcohol use than to cannabis use. Several limitations exist in the literature. Sample sizes are relatively small and demographically homogenous, with significant heterogeneity in substance use patterns and methodologies across studies. More research is needed to clarify how substance dosing and interactions between substances, as well as sociodemographic and environmental factors, affect outcomes. Larger longitudinal studies, already underway, will help clarify the relationship between brain development and substance use.

Neuropsychological and neurophysiological predictors and consequences of cannabis and illicit substance use during neurodevelopment: a systematic review of longitudinal studies.

Adolescence and early adulthood are crucial periods of neurodevelopment characterised by functional, structural, and cognitive maturation, which helps prepare young people for adulthood. This systematic review of longitudinal studies aims to delineate neural predictors from neural consequences of cannabis and illicit substance use, as well as investigate the potential for the developing brain (at ages 10-25 years) to recover after damage. Five databases were searched to yield a total of 38 eligible studies, with some assessing multiple outcome techniques, including 22 neuroimaging, two neurophysiological, and 22 neuropsychological findings. High-quality evidence suggested that delayed or irregular neurodevelopment in executive functioning, particularly emotional perception, might predispose young people to higher frequency substance use. There was evidence of functional, structural, and cognitive deficits proceeding substance use, with harm potentially dependent on the frequency of use and recovery potentially dependent on the duration of use. Identifying aberrant neurodevelopment in young people is crucial for preventing substance use-related harm.

Problems experienced by children from families with histories of substance misuse: An ABCD study®.

BACKGROUND: There are significant knowledge gaps of the vulnerabilities faced by youth from families with histories of alcohol or substance misuse. This study aimed to provide a comprehensive assessment of problems experienced by substance-naive children with positive family histories of substance misuse (FHP). METHODS: Baseline data from up to 11,873 children (52.1 % male), aged 9.0-10.9 years (M = 9.9 ± 0.6), enrolled in the US-based Adolescent Brain Cognitive Development Study® were utilized. Mixed models tested cross-sectional associations between family history of substance misuse, assessed categorically and continuously, with neurobiological, cognitive, behavioral, and psychological outcomes, when controlling for confounding factors, including family history of psychopathology, and correcting for multiple comparisons. RESULTS: One in four (26.3 %) youth were categorized as FHP (defined as ≥ one parent or ≥ two grandparents with misuse history). Controlling for confounding, FHP youth exhibited thinner whole cortices and greater surface area in frontal and occipital regions than youth with no such history (|ds|≥0.04, ps<.001). FHP youth experienced greater psychopathology and sleep disturbance (|ds|≥0.36, ps<.001) and were more likely to be diagnosed with multiple mental disorders (odds ratios≥1.22, ps<.001), with severity of effects dependent on family history density of substance misuse. Differences in cognition, impulsivity, and motivation were non-significant. Psychopathology, mental disorders, and sleep disturbance were negatively correlated with various neural indices (|rs|=0.01-0.05, ps<.05). CONCLUSIONS: At age 9-10 years, FHP youth can experience numerous problems, with psychopathology and mental disorders being some of the most significant. Therefore, prevention efforts should target psychopathology vulnerabilities in FHP children.

An ecological model of drug and alcohol use and related harms among Aboriginal and Torres Strait Islander Australians: A systematic review of the literature.

Globally, Indigenous populations experience a disproportionately higher burden of disease related to substance use. Effective prevention of harm related to substance use is a key strategy for improving the health and wellbeing of Aboriginal and Torres Strait Islander peoples in Australia. To inform preventative approaches, this review synthesised the evidence of risk and protective factors of substance use and related harms among Aboriginal and Torres Strait Islander peoples. Eight peer-reviewed and two grey literature databases were systematically searched for quantitative or qualitative studies assessing factors associated with substance use and related harms among Aboriginal and Torres Strait Islander peoples, published between 1 January 1990 and 30 April 2018. Study quality was assessed using validated instruments. Risk or odds ratios were extracted or calculated and factors were summarised in an ecological model into individual, relationship, community, societal or culturally-distinct levels. Thirty-eight relevant studies were identified and reviewed. Individual-level risk factors for substance use were identified including low socio-economic status, high psychological distress, poly drug use and being male. Relationship-level factors were peer pressure and partner/family substance use; protective factors were supportive environments and positive role models. Community-level risk factors included availability of substances. Culturally-distinct factors included cultural connection as a protective factor, but cultural obligations around sharing was a risk factor. Societal risk factors included intergenerational trauma caused by government policies. These findings highlight the importance of tailored preventative approaches for Aboriginal and Torres Strait Islander communities that address identified risk factors and promote protective factors across all ecological levels.

Diffusion Tensor Imaging in Sport-Related Concussion: A Systematic Review Using an a priori Quality Rating System.

Diffusion tensor imaging (DTI) of brain white matter (WM) may be useful for characterizing the nature and degree of brain injury after sport-related concussion (SRC) and assist in establishing objective diagnostic and prognostic biomarkers. This study aimed to conduct a systematic review using an a priori quality rating strategy to determine the most consistent DTI-WM changes post-SRC. Articles published in English (until June 2020) were retrieved by standard research engine and gray literature searches (N = 4932), using PRISMA guidelines. Eligible studies were non-interventional naturalistic original studies that conducted DTI within 6 months of SRC in current athletes from all levels of play, types of sports, and sex. A total of 29 articles were included in the review, and after quality appraisal by two raters, data from 10 studies were extracted after being identified as high quality. High-quality studies showed widespread moderate-to-large WM differences when SRC samples were compared to controls during the acute to early chronic stage (days to weeks) post-SRC, including both increased and decreased fractional anisotropy and axial diffusivity and decreased mean diffusivity and radial diffusivity. WM differences remained stable in the chronic stage (2-6 months post-SRC). DTI metrics were commonly associated with SRC symptom severity, although standardized SRC diagnostics would improve future research. This indicates that microstructural recovery is often incomplete at return to play and may lag behind clinically assessed recovery measures. Future work should explore interindividual trajectories to improve understanding of the heterogeneous and dynamic WM patterns post-SRC.

Are we making Inroads? A randomized controlled trial of a psychologist-supported, web-based, cognitive behavioral therapy intervention to reduce anxiety and hazardous alcohol use among emerging adults.

BACKGROUND: Anxiety and alcohol use disorders are common and disabling conditions that people typically endure for many years before accessing treatment. The link between anxiety and alcohol use is well-established, with these issues commonly emerging and/or escalating during emerging adulthood. This randomized controlled trial evaluated a psychologist-supported, web-based intervention, designed with and for emerging adults, that aims to promote adaptive coping strategies, and prevent anxiety and alcohol use from progressing to chronic, mutually-reinforcing disorders. METHODS: Between December 2017 and September 2018, 123 emerging adults (aged 17-24) reporting anxiety symptoms and hazardous alcohol use were randomized to receive the Inroads or control (assessment plus alcohol information) intervention. The Inroads program combined five web-based cognitive behavioral therapy modules with weekly psychologist support via email/phone. Primary outcomes were alcohol consumption, severity of alcohol-related consequences, and general anxiety symptoms, assessed at baseline, 2 and 6-months post-baseline. Secondary outcomes included hazardous alcohol use and social anxiety. Trial Registration: Prospectively registered in the Australian New Zealand Clinical Trials Registry, ACTRN12617001609347. FINDINGS: Alcohol consumption and associated consequences reduced in both groups, with the Inroads group reporting greater alcohol reductions by 6-month follow-up (mean difference -0.74, 95% CI: -1.47 to -0.01, d = 0.24). Relative to controls, hazardous alcohol use reduced among Inroads participants at both follow-ups (2-month mean difference -2.14, 95% CI: -4.06 to -0.22). Inroads participants also reported reduced symptoms of general (mean difference -3.06, 95% CI: -4.97 to -1.15, d = 0.88) and social anxiety (mean difference -3.21, 95% CI: -6.34 to -0.07, d = 0.32) at 2-month follow-up, with improvements in social anxiety sustained at 6-months. INTERPRETATION: The Inroads program demonstrated beneficial effects on alcohol consumption, hazardous alcohol use, and anxiety symptoms. The web-based format is aligned with youth treatment preferences and can be delivered at scale to achieve wide dissemination and reduce the significant burden associated with these chronic, mutually reinforcing conditions. FUNDING: Australian Rotary Health, Australian National Health and Medical Research Council.

Promising vulnerability markers of substance use and misuse: A review of human neurobehavioral studies.

Substance use often begins, and noticeably escalates, during adolescence. Identifying predictive neurobehavioral vulnerability markers of substance use and related problems may improve targeted prevention and early intervention initiatives. This review synthesizes 44 longitudinal studies and explores the utility of developmental imbalance models and neurobehavioral addiction frameworks in predicting neural and cognitive patterns that are associated with prospective substance use initiation and escalation among young people. A total of 234 effect sizes were calculated and compared. Findings suggest that aberrant neural structure and function of regions implicated in reward processing, cognitive control, and impulsivity can predate substance use initiation, escalation, and disorder. Functional vulnerability markers of substance use include hyperactivation during reward feedback and risk evaluation in prefrontal and ventral striatal regions, fronto-parietal hypoactivation during working memory, distinctive neural patterns during successful (fronto-parietal hyperactivation) and failed response inhibition (frontal hypoactivation), and related cognitive deficits. Structurally, smaller fronto-parietal and amygdala volume and larger ventral striatal volume predicts prospective substance misuse. Taken together, the findings of this review suggest that neurobehavioral data can be useful in predicting future substance use behaviors. Notably, little to no research has empirically tested the underlying assumptions of widely used theoretical frameworks. To improve the reliability and utility of neurobehavioral data in predicting future substance use behaviors, recommendations for future research are provided. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'

Fetal Alcohol Spectrum Disorder resources for educators working within primary school settings: a scoping review protocol.

INTRODUCTION: Many children affected by Fetal Alcohol Spectrum Disorder (FASD) exhibit neurocognitive delays that contribute to secondary consequences, including a disrupted school experience. Educators often have limited knowledge or experience in the identification, referral, management and accommodation of students with FASD. Effective resources and tools for educators are crucial to ensure these students are supported in their ongoing learning, development and school participation. This scoping review aims to identify and evaluate resources for educators that aid in the identification, management, or accommodation of students with FASD. METHODS AND ANALYSIS: A search will be conducted in 9 peer-reviewed and 11 grey literature databases, Google search engine, two app stores and two podcast streaming services (planned search dates: November 2020 to February 2021). Relevant experts, including researchers, health professionals and individuals with lived experience of FASD, will be contacted in February and March 2021 to identify additional (including unpublished) resources. Resources will be selected based on registered, prespecified inclusion-exclusion criteria, and the quality of included resources will be critically appraised using a composite tool based on adaptions of the National Health and Medical Research Council FORM Framework and the iCAHE Guideline Quality Checklist. Relevant experts will also be requested to provide feedback on included resources. ETHICS AND DISSEMINATION: Ethical approval for this scoping review was obtained from the University of Sydney Human Research Ethics Committee (2020/825). Results of the review will be disseminated through a peer-reviewed publication, conference presentations, and seminars targeting audiences involved in the education sector. TRIAL REGISTRATION: Open Science Framework: osf.io/73pjh.

Strong and Deadly Futures: Co-Development of a Web-Based Wellbeing and Substance Use Prevention Program for Aboriginal and Torres Strait Islander and Non-Aboriginal Adolescents.

School-based programs can effectively prevent substance use; however, systematic reviews and consultation with stakeholders identified a need for effective, culturally inclusive programs for Aboriginal and/or Torres Strait Islander (hereafter Aboriginal) youth. This paper describes the development of Strong & Deadly Futures, a six-lesson, curriculum-aligned wellbeing and substance use prevention program that was designed for, and with, the Aboriginal youth. Formative reviews and consultation recommended that the program (i) combine effective components of mainstream prevention with cultural elements, highlighting Aboriginal cultural strengths; (ii) avoid stigma and celebrates the cultural diversity by catering to both Aboriginal and non-Aboriginal students; and (iii) use digital technology to enhance engagement, implementation and scalability. Guided by an Appreciative Inquiry approach, the program was developed in partnership with an Indigenous Creative Design Agency, and four schools in New South Wales and Queensland, Australia. Aboriginal (n = 41) and non-Aboriginal students (n = 36) described their role models, positive aspects of their community and reasons to avoid substance use; these formed the basis of an illustrated story which conveyed the key learning outcomes. Feedback from teachers, students and content experts supported the acceptability of the program, which will be evaluated in a subsequent randomised controlled trial.

Altered Neurocognitive Functional Connectivity and Activation Patterns Underlie Psychopathology in Preadolescence.

BACKGROUND: Neurocognitive deficits are common among youth with mental disorders, and patterns of aberrant brain function generally cross diagnostic boundaries. This study investigated associations between functional neurocircuitry and broad transdiagnostic psychopathology dimensions in the critical preadolescent period when psychopathology is emerging. METHODS: Participants were 9- to 10-year-olds from the Adolescent Brain Cognitive Development Study. Factor scores of general psychopathology, externalizing, internalizing, and thought disorder dimensions were calculated from a higher-order model of psychopathology using confirmatory factor analysis (N = 11,721) and entered as explanatory variables into linear mixed models to examine associations with resting-state functional connectivity (n = 9074) and neural activation during the emotional n-back task (n = 6146) when covarying for sex, race/ethnicity, parental education, and cognitive function. RESULTS: All dimensions of psychopathology were commonly characterized by hypoconnectivity within the dorsal attention and retrosplenial-temporal networks, hyperconnectivity between the frontoparietal and ventral attention networks and between the dorsal attention network and amygdala, and hypoactivation of the caudal middle frontal gyrus. Externalizing pathology was uniquely associated with hyperconnectivity between the salience and ventral attention networks and hyperactivation of the cingulate and striatum. Internalizing pathology was uniquely characterized by hypoconnectivity between the default mode and cingulo-opercular networks. Connectivity between the cingulo-opercular network and putamen was uniquely higher for internalizing pathology and lower for thought disorder pathology. CONCLUSIONS: These findings provide novel evidence that broad psychopathology dimensions are characterized by common and dissociable patterns, particularly for externalizing pathology, of functional connectivity and task-evoked activation throughout neurocognitive networks in preadolescence.

Association of prenatal alcohol exposure with preadolescent alcohol sipping in the ABCD study®.

BACKGROUND: Early alcohol use initiation is one of the strongest predictors of alcohol use disorders. Identifying modifiable risk factors for problematic alcohol use can guide prevention initiatives. Globally, approximately 10% of women consume alcohol during pregnancy, however the impact of prenatal alcohol exposure (PAE) on offspring alcohol use patterns has been understudied. The aim of this study was to examine associations between PAE and preadolescent alcohol use behaviors. METHODS: Cross-sectional data were utilized from 10,119 children aged 9.0-10.9 years (M = 9.9, SD = 0.6) enrolled in the Adolescent Brain Cognitive Development Study®, based in the United States. Linear mixed models tested associations between PAE and endorsement of non-religious alcohol sipping in offspring, when adjusting for confounding factors. RESULTS: In total, 2675 (26.4 %) youth were prenatally exposed to alcohol. Among PAE youth, total standard drinks consumed during pregnancy ranged from 0.4-90.0 drinks (M = 26.8, SD = 24.5). Compared to unexposed youth, those with any alcohol exposure during early pregnancy (∼0-7 weeks) were 1.7 times (95 % CI 1.4-2.0, p < .0001) more likely to endorse sipping alcohol by ages 9-10, while youth with low-level doses of alcohol throughout the entire pregnancy were 2.9 times (95 % CI 1.9-4.6, p < .0001) more likely to endorse sipping, when adjusting for confounding factors. A dose-dependent association between total standard drinks consumed during pregnancy and youth sipping endorsement was observed (ß = 0.2, 95 % CI 0.1-0.2, p < .0001). CONCLUSIONS: This study shows that any alcohol use during pregnancy may play an important role in very early alcohol use experimentation among offspring by ages 9-10.

A randomised double-blind trial of cognitive training for the prevention of psychopathology in at-risk youth.

BACKGROUND: The aim of this study was to evaluate the effectiveness of online cognitive training as a means of reducing psychopathology in at-risk youth. METHODS: In a double-blind randomised controlled trial, 228 youths (mean age = 18.6, 74.6% female) were randomly allocated to either an intervention group (n = 114; online cognitive training focused on executive functioning) and a control group (n = 114; online cognitive training focused on other cognitive abilities). Participants were assessed online at baseline, post-training, 3-, 6- and 12-month follow-up. The primary outcome of the study was overall psychopathology as measured by the Strengths and Difficulties Questionnaire. Secondary outcomes were executive functioning ability (assessed using the n-back, trail-making and Stroop tasks), day-to-day functioning and risky drinking. RESULTS: Mixed model intention-to-treat analyses indicated that psychopathology increased and day-to-day functioning decreased, regardless of intervention group. Those in the intervention group improved more than those in the control group in terms of the n-back task, but this was not statistically significant after adjusting for multiple comparisons. There were no statistically significant effects on risky drinking, or the trail-making and Stroop tasks. CONCLUSION: This study failed to provide evidence for the efficacy of cognitive training as a stand-alone intervention for psychopathology.

Cannabis and Illicit Drug Use During Neurodevelopment and the Associated Structural, Functional and Cognitive Outcomes: Protocol for a Systematic Review.

BACKGROUND: High rates of cannabis and illicit drug use are experienced by young people during the final stages of neurodevelopment (aged 15-24 years), a period characterized by high neuroplasticity. Frequent drug use during this time may interfere with neurophysiological and neuropsychological development pathways, potentially leading to ongoing unfavorable neuroadaptations. The dose-response relationship between illicit drug use, exposure, and individual neurodevelopmental variation is unknown but salient with global shifts in the legal landscape and increasingly liberal attitudes and perceptions of the harm caused by cannabis and illicit drugs. OBJECTIVE: This systematic review aims to synthesize longitudinal studies that investigate the effects of illicit drug use on structural, functional, and cognitive brain domains in individuals under the neural age of adulthood (25 years). This protocol outlines prospective methods that will facilitate an exhaustive review of the literature exploring pre- and post-drug use brain abnormalities arising during neurodevelopment. METHODS: Five electronic databases (Medline, Embase, PsycINFO, ProQuest Central, and Web of Science) will be systematically searched between 1990 and 2019. The search terms will be a combination of MeSH (Medical Subject Headings), with keywords adapted to each database. Study reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and if relevant, study quality will be assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Eligible studies are those that sampled youth exposed to cannabis or illicit drugs and employed neurophysiological or neuropsychological assessment techniques. Studies will be excluded if participants had been clinically diagnosed with any psychiatric, neurological, or pharmacological condition. RESULTS: This is an ongoing review. As of February 2020, papers are in full-text screening, with results predicted to be complete by July 2020. CONCLUSIONS: Integrating data collected on the three brain domains will enable an assessment of the links between structural, functional, and cognitive brain health across individuals and may support the early detection and prevention of neurodevelopmental harm. TRIAL REGISTRATION: PROSPERO CRD42020151442; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=151442. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18349.