Associations between perinatal risk and physical health in pre-adolescence in the Adolescent Brain Cognitive Development (ABCD) Study®: the unexpected relationship with sleep disruption.

BACKGROUND: To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems. METHODS: A cross-sectional study was conducted utilizing the Adolescent Brain Cognitive Development℠ (ABCD) Study (n = 7613, ages 9-to-10-years-old) to determine the associations among multiple physical health factors (e.g., prenatal complications, current physical health problems). Logistic regression models controlling for age, sex, pubertal development, household income, caregiver education, race, and ethnicity evaluated relationships between perinatal factors and childhood physical health problems. RESULTS: There were significant associations between perinatal and current physical health measures. Specifically, those who had experienced perinatal complications were more likely to have medical problems by 9-to-10 years old. Importantly, sleep disturbance co-occurred with several physical health problems across domains and developmental periods. CONCLUSION: Several perinatal health factors were associated with childhood health outcomes, highlighting the importance of understanding and potentially improving physical health in youth. Understanding the clustering of physical health problems in youth is essential to better identify which physical health problems may share underlying mechanisms. IMPACT: Using a multivariable approach, we investigated the associations between various perinatal and current health problems amongst youth. Our study highlights current health problems, such as sleep problems at 9-to-10 years old, that are associated with a cluster of factors occurring across development (e.g., low birth weight, prenatal substance exposure, pregnancy complications, current weight status, lifetime head injury). Perinatal health problems are at large, non-modifiable (in this retrospective context), however, by identifying which are associated with current health problems, we can identify potential targets for intervention and prevention efforts.

Pre-pandemic circadian phase predicts pandemic alcohol use among adolescents.

Later circadian timing during adolescence is linked to worse sleep, more severe depression and greater alcohol involvement, perhaps due to circadian misalignment imposed by early school schedules. School schedules shifted later during the COVID-19 pandemic, ostensibly reducing circadian misalignment and potentially mitigating problems with depression and alcohol. We used the pandemic as a natural experiment to test whether adolescent drinkers with later circadian timing showed improvements in sleep, depression and alcohol involvement. Participants were 42 adolescents reporting alcohol use. We assessed circadian phase via dim light melatonin onset prior to the pandemic, then conducted remote assessments of sleep, depressive symptoms and alcohol use during the pandemic. Mixed-effects models were used to test for pandemic effects, covarying for age, sex, time since baseline evaluation, and current school/work status. Adolescents with later circadian timing reported less sleep than other teens on school nights, both before and during the pandemic. Although school night sleep increased during the pandemic (F = 28.36, p < 0.001), those increases were not greater for individuals with later circadian timing. Individuals with later circadian timing reported larger increases in alcohol use than other teens during the pandemic (X2 = 36.03, p < 0.001). Depressive symptoms increased during the pandemic (X2 = 46.51, p < 0.001) but did not differ based on circadian timing. Consistent with prior reports, adolescents with later circadian timing obtained less sleep, and later school schedules facilitated increased sleep duration. Nonetheless, individuals with later circadian timing reported the sharpest increases in alcohol use, suggesting that circadian timing contributes to risk for alcohol use beyond the effects of insufficient sleep.

Risk for depression tripled during the COVID-19 pandemic in emerging adults followed for the last 8 years.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic. METHODS: Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms. RESULTS: The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms. CONCLUSIONS: The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.

Morning perception of sleep, stress, and mood, and its relationship with overnight physiological sleep: findings from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study.

This cross-sectional study investigated objective-subjective sleep discrepancies and the physiological basis for morning perceptions of sleep, mood, and readiness, in adolescents. Data collected during a single in-laboratory polysomnographic assessment from 137 healthy adolescents (61 girls; age range: 12-21 years) in the United States National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study were analysed. Upon awakening, participants completed questionnaires assessing sleep quality, mood, and readiness. We evaluated the relationship between overnight polysomnographic, electroencephalographic, sleep autonomic nervous system functioning measures, and next morning self-reported indices. Results showed that older adolescents reported more awakenings, yet they perceived their sleep to be deeper and less restless than younger adolescents. Prediction models including sleep physiology measures (polysomnographic, electroencephalographic, and sleep autonomic nervous system) explained between 3% and 29% of morning sleep perception, mood, and readiness indices. The subjective experience of sleep is a complex phenomenon with multiple components. Distinct physiological sleep processes contribute to the morning perception of sleep and related measures of mood and readiness. More than 70% of the variance (based on a single observation per person) in the perception of sleep, mood, and morning readiness is not explained by overnight sleep-related physiological measures, suggesting that other factors are important for the subjective sleep experience.

Self-reported sleep and circadian characteristics predict alcohol and cannabis use: A longitudinal analysis of the National Consortium on Alcohol and Neurodevelopment in Adolescence Study.

BACKGROUND: Growing evidence indicates that sleep characteristics predict future substance use and related problems. However, most prior studies assessed a limited range of sleep characteristics, studied a narrow age span, and included few follow-up assessments. Here, we used six annual assessments from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study, which spans adolescence and young adulthood with an accelerated longitudinal design, to examine whether multiple sleep characteristics in any year predict alcohol and cannabis use the following year. METHODS: The sample included 831 NCANDA participants (423 females; baseline age 12-21 years). Sleep variables included circadian preference, sleep quality, daytime sleepiness, the timing of midsleep (weekday/weekend), and sleep duration (weekday/weekend). Using generalized linear mixed models (logistic for cannabis; ordinal for binge severity), we tested whether each repeatedly measured sleep characteristic (years 0-4) predicted substance use (alcohol binge severity or cannabis use) the following year (years 1-5), covarying for age, sex, race, visit, parental education, and previous year's substance use. RESULTS: Greater eveningness, more daytime sleepiness, later weekend sleep timing, and shorter sleep duration (weekday/weekend) all predicted more severe alcohol binge drinking the following year. Only greater eveningness predicted a greater likelihood of any cannabis use the following year. Post-hoc stratified exploratory analyses indicated that some associations (e.g., greater eveningness and shorter weekend sleep duration) predicted binge severity only in female participants, and that middle/high school versus post-high school adolescents were more vulnerable to sleep-related risk for cannabis use. CONCLUSIONS: Our findings support the relevance of multiple sleep/circadian characteristics in the risk for future alcohol binge severity and cannabis use. Preliminary findings suggest that these risk factors vary based on developmental stage and sex. Results underscore a need for greater attention to sleep/circadian characteristics as potential risk factors for substance use in youth and may inform new avenues to prevention and intervention.

Prior test experience confounds longitudinal tracking of adolescent cognitive and motor development.

BACKGROUND: Accurate measurement of trajectories in longitudinal studies, considered the gold standard method for tracking functional growth during adolescence, decline in aging, and change after head injury, is subject to confounding by testing experience. METHODS: We measured change in cognitive and motor abilities over four test sessions (baseline and three annual assessments) in 154 male and 165 female participants (baseline age 12-21 years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. At each of the four test sessions, these participants were given a test battery using computerized administration and traditional pencil and paper tests that yielded accuracy and speed measures for multiple component cognitive (Abstraction, Attention, Emotion, Episodic memory, Working memory, and General Ability) and motor (Ataxia and Speed) functions. The analysis aim was to dissociate neurodevelopment from testing experience by using an adaptation of the twice-minus-once tested method, which calculated the difference between longitudinal change (comprising developmental plus practice effects) and practice-free initial cross-sectional performance for each consecutive pairs of test sessions. Accordingly, the first set of analyses quantified the effects of learning (i.e., prior test experience) on accuracy and after speed domain scores. Then developmental effects were  determined for each domain for accuracy and speed having removed the measured learning effects. RESULTS: The greatest gains in performance occurred between the first and second sessions, especially in younger participants, regardless of sex, but practice gains continued to accrue thereafter for several functions. For all 8 accuracy composite scores, the developmental effect after accounting for learning was significant across age and was adequately described by linear fits. The learning-adjusted developmental effects for speed were adequately described by linear fits for Abstraction, Emotion, Episodic Memory, General Ability, and Motor scores, although a nonlinear fit was better for Attention, Working Memory, and Average Speed scores. CONCLUSION: Thus, what appeared as accelerated cognitive and motor development was, in most cases, attributable to learning. Recognition of the substantial influence of prior testing experience is critical for accurate characterization of normal development and for developing norms for clinical neuropsychological investigations of conditions affecting the brain.

Developmental trajectories of Big Five personality traits among adolescents and young adults: Differences by sex, alcohol use, and marijuana use.

OBJECTIVE: Individual differences in adolescent personality are related to a variety of long-term health outcomes. While previous studies have demonstrated sex differences and non-linear changes in personality development, these results remain equivocal. The current study utilized longitudinal data (n = 831) from the National Consortium on Alcohol and Neurodevelopment in Adolescence to examine sex differences in the development of personality and the association between substance use and personality. METHOD: Participants (ages 12-21 at baseline) completed the Ten-Item Personality Inventory and self-reported past year alcohol and marijuana use at up to 7 yearly visits. Data were analyzed using generalized additive mixed-effects models and linear mixed-effects models. RESULTS: Findings support linear increases in agreeableness and conscientious and decreases in openness with age and inform on timing of sex-specific non-linear development of extraversion and emotional stability. Further, results provide novel information regarding the timing of the association between substance use and personality, and replicate past reporting of differential associations between alcohol and marijuana use and extraversion, and sex-dependent effects of marijuana use on emotional stability. CONCLUSIONS: These findings highlight the importance of modeling sex differences in personality development using flexible non-linear modeling strategies, and accounting for sex- and age-specific effects of alcohol and marijuana use.

Experimentally imposed circadian misalignment alters the neural response to monetary rewards and response inhibition in healthy adolescents.

BACKGROUND: Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition. METHODS: Healthy adolescents (n = 25, ages 13-17) completed two in-lab sleep schedules in counterbalanced order: An 'aligned' condition based on typical summer sleep-wake times (0000-0930) and a 'misaligned' condition mimicking earlier school year sleep-wake times (2000-0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively. RESULTS: Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan. CONCLUSIONS: Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.

Associations of developmental imbalance between sensation seeking and premeditation in adolescence and heavy episodic drinking in emerging adulthood.

BACKGROUND: Dual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood. METHODS: Prospective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n = 715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20 years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex. RESULTS: Whereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r = 0.86) with baseline levels of sensation seeking. CONCLUSIONS: Developmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.

Adolescent alcohol use disrupts functional neurodevelopment in sensation seeking girls.

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.

Longitudinal Impact of Life Events on Adolescent Binge Drinking in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA).

Background: Life events experienced during adolescence are associated with risk and resilience to heavy episodic drinking (HED; i.e. binge drinking). The current study builds on prior research using latent class analysis (LCA) to examine heterogeneity in patterns of adolescent life events at baseline to HED over the course of three years (4 timepoints) as part of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). Methods: Life event classes were modeled using LCA that characterized NCANDA participants based upon their responses to the Life Events Questionnaire (N = 467, age: M = 14.98, SD = 1.69, 49.7% female). These baseline latent life event classes were then compared to HED at baseline and years 1, 2 and 3 using multinomial logistic regression. Results: At baseline, the LCA characterized four classes of adolescents based on endorsement of life events: negative-relational conflict (n = 65, 13.9%), negative-financial problems (n = 49, 10.5%), low life events (n = 130, 27.8%), and positive life events (n = 223, 47.8%). Life event trajectories differed for the negative life event classes compared to the other two classes, with greater odds of HED in the negative-financial problems class at year 1. Conclusion: The four latent classes derived from the life events of NCANDA youth yielded a characterization of adolescents that could aid in understanding HED over the subsequent three years, suggesting that everyday life events may inform adolescent binge drinking.

Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains.

The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors.

Algorithm Analysis of the DSM-5 Alcohol Withdrawal Symptom.

BACKGROUND: Alcohol withdrawal (AW) is an important clinical and diagnostic feature of alcohol dependence. AW has been found to predict a worsened course of illness in clinical samples, but in some community studies, AW endorsement rates are strikingly high, suggesting false-positive symptom assignments. Little research has examined the validity of the DSM-5 algorithm for AW, which requires either the presence of at least 2 of 8 subcriteria (i.e., autonomic hyperactivity, tremulousness, insomnia, nausea, hallucinations, psychomotor agitation, anxiety, and grand mal seizures), or, the use of alcohol to avoid or relieve these symptoms. METHODS: We used item and algorithm analyses of data from waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (current drinkers, n = 26,946 at wave 1) to study the validity of DSM-5 AW as operationalized by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV (AUDADIS-IV). RESULTS: A substantial proportion of individuals given the AW symptom reported only modest to moderate levels of alcohol use and alcohol problems. Alternative AW algorithms were superior to DSM-5 in terms of levels of alcohol use and alcohol problem severity among those with AW, group difference effect sizes, and predictive validity at a 3-year follow-up. The superior alternative algorithms included those that excluded the nausea subcriterion; required withdrawal-related distress or impairment; increased the AW subcriteria threshold from 2 to 3 items; and required tremulousness for AW symptom assignment. CONCLUSIONS: The results indicate that the DSM-5 definition of AW, as assessed by the AUDADIS-IV, has low specificity. This shortcoming can be addressed by making the algorithm for symptom assignment more stringent.

Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol and Marijuana Use in Adolescence: Initial Findings from the National Consortium on Alcohol and Neurodevelopment in Adolescence Study.

BACKGROUND: Abundant cross-sectional evidence links eveningness (a preference for later sleep-wake timing) and increased alcohol and drug use among adolescents and young adults. However, longitudinal studies are needed to examine whether eveningness is a risk factor for subsequent alcohol and drug use, particularly during adolescence, which is marked by parallel peaks in eveningness and risk for the onset of alcohol use disorders. This study examined whether eveningness and other sleep characteristics were associated with concurrent or subsequent substance involvement in a longitudinal study of adolescents. METHODS: Participants were 729 adolescents (368 females; age 12 to 21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence study. Associations between the sleep variables (circadian preference, sleep quality, daytime sleepiness, sleep timing, and sleep duration) and 3 categorical substance variables (at-risk alcohol use, alcohol bingeing, and past-year marijuana use [y/n]) were examined using ordinal and logistic regression with baseline age, sex, race, ethnicity, socioeconomic status, and psychiatric problems as covariates. RESULTS: At baseline, greater eveningness was associated with greater at-risk alcohol use, greater bingeing, and past-year use of marijuana. Later weekday and weekend bedtimes, but not weekday or weekend sleep duration, showed similar associations across the 3 substance outcomes at baseline. Greater baseline eveningness was also prospectively associated with greater bingeing and past-year use of marijuana at the 1-year follow-up, after covarying for baseline bingeing and marijuana use. Later baseline weekday and weekend bedtimes, and shorter baseline weekday sleep duration, were similarly associated with greater bingeing and past-year use of marijuana at the 1-year follow-up after covarying for baseline values. CONCLUSIONS: Findings suggest that eveningness and sleep timing may be under recognized risk factors and future areas of intervention for adolescent involvement in alcohol and marijuana that should be considered along with other previously identified sleep factors such as insomnia and insufficient sleep.

Adolescent Development of Cortical and White Matter Structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking.

Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development.

Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study.

Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.

Screening for Underage Drinking and Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Alcohol Use Disorder in Rural Primary Care Practice.

OBJECTIVE: To examine the National Institute on Alcohol Abuse and Alcoholism Youth Guide alcohol frequency screening thresholds when applied to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria, and to describe alcohol use patterns and alcohol use disorder (AUD) characteristics in rural youth from primary care settings. STUDY DESIGN: Adolescents (n = 1193; ages 12 through 20 years) visiting their primary care practitioner for outpatient visits in six rural primary care clinics were assessed prior to their practitioner visit. A tablet computer collected youth self-report of past-year frequency and quantity of alcohol use and DSM-5 AUD symptoms. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: For early adolescents (ages 12 through 14 years), 1.9% met DSM-5 criteria for past-year AUD and ≥3 days with alcohol use in the past year yielded a screen for DSM-5 with optimal psychometric properties (sensitivity: 89%; specificity: 95%; PPV: 37%; NPV: 100%). For middle adolescents (ages 15 through 17 years), 9.5% met DSM-5 AUD criteria, and ≥3 past year drinking days showed optimal screening results (sensitivity: 91%; specificity: 89%; PPV: 50%; NPV: 99%). For late adolescents (ages 18 through 20 years), 10.0% met DSM-5 AUD criteria, and ≥12 past year drinking days showed optimal screening results (sensitivity: 92%; specificity: 75%; PPV: 31%; NPV: 99%). The age stratified National Institute on Alcohol Abuse and Alcoholism frequency thresholds also produced effective results. CONCLUSION: In rural primary care clinics, 10% of youth over age 14 years had a past-year DSM-5 AUD. These at-risk adolescents can be identified with a single question on alcohol use frequency.

Child Temperamental Flexibility Moderates the Relation between Positive Parenting and Adolescent Adjustment.

Temperamental flexibility and lower positive parenting are associated with internalizing and externalizing problems; however, youth varying in flexibility may be differentially affected by positive parenting in the prediction of symptoms. We examined whether children's flexibility moderated prospective relations between maternal and paternal positive parenting and youth internalizing and externalizing symptoms during adolescence. Participants (N =775, 71% male) and their caregivers completed measures when youth were 10-12 and 12-14 years old. Father positive parenting interacted with child flexibility to predict father-reported internalizing and externalizing problems. Consistent with the diathesis-stress model, children lower in flexibility experienced greater symptoms than children higher in flexibility in lower positive parenting contexts. Among children lower in flexibility, lower paternal positive parenting was associated with greater internalizing and externalizing symptoms compared to higher paternal positive parenting. However, among youth higher in flexibility, symptom levels were similar regardless of whether youth experienced lower or higher paternal positive parenting.

Course of alcohol symptoms and social anxiety disorder from adolescence to young adulthood.

BACKGROUND: There is limited knowledge of the course of social anxiety disorder (SAD) from adolescence into adulthood, and how SAD and alcohol use disorder (AUD) symptoms change together over time. The current study examined how persistent and adolescent-limited SAD relate to alcohol symptom trajectories across adolescence and into adulthood, as well as gender differences in the course of SAD and AUD symptoms. METHODS: Participants were 788 youth (ages 12 to 18 at the baseline assessment; 46.2% female; 80.5% White) recruited from the community (n = 220) and from clinical programs (n = 568). Youth completed clinical interviews on their lifetime history of AUD symptoms and SAD at baseline and were followed through age 25. Multivariate polynomial growth mixture modeling was used to estimate developmental trajectories for SAD and AUD symptoms separately, then together in a dual trajectory model. Gender differences were examined using a classify-analyze approach. RESULTS: Three SAD trajectory classes were identified: adolescent-limited (15%), persistent (6%), and no SAD (79%). For AUD symptoms, 5 trajectories were identified: severe (10%), moderate (22%), remitting (18%), young adult onset (22%), and stable low (28%). Those with a history of SAD were about twice as likely to be in the severe AUD symptom class compared to those without a history of SAD. Compared to those with persisting SAD, those in the adolescent-limited SAD class were more likely to belong to the stable low AUD trajectory. Compared to males with SAD, females with SAD were less likely to be in the moderate AUD symptom class and were more likely to be in stable low and young adult onset AUD symptom classes. CONCLUSIONS: A history of SAD was associated with membership in the severe AUD trajectory group. The association of gender with SAD and AUD differed depending on developmental period. Future research should examine whether treating SAD in early adolescence may prevent subsequent AUD symptoms.

A Hierarchical Factor Model of Executive Functions in Adolescents: Evidence of Gene-Environment Interplay.

Executive functions (EF) are a complex set of neurodevelopmental, higher-ordered processes that are especially salient during adolescence. Disruptions to these processes are predictive of psychiatric problems in later adolescence and adulthood. The objectives of the current study were to characterize the latent structure of EF using bifactor analysis and to investigate the independent and interactive effects of genes and environments on EF during adolescence. Using a representative young adolescent sample, we tested the interaction of a polymorphism in the serotonin transporter gene (5-HTTLPR) and parental supervision for EF through hierarchical linear regression. To account for the possibility of a hierarchical factor structure for EF, a bifactor analysis was conducted on the eight subtests of the Delis-Kaplan Executive Functions System (D-KEFS). The bifactor analysis revealed the presence of a general EF construct and three EF subdomains (i.e., conceptual flexibility, inhibition, and fluency). A significant 5-HTTLPR by parental supervision interaction was found for conceptual flexibility, but not for general EF, fluency or inhibition. Specifically, youth with the L/L genotype had significantly lower conceptual flexibility scores compared to youth with S/S or S/L genotypes given low levels of parental supervision. Our findings indicate that adolescents with the L/L genotype were especially vulnerable to poor parental supervision on EF. This vulnerability may be amenable to preventive interventions.