Objective:The cerebellum is a target of alcoholism-related brain damage in adults. Yet no study h... more Objective:The cerebellum is a target of alcoholism-related brain damage in adults. Yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking.Method:MRI tracked developmental volume trajectories of 10 cerebellar lobule and vermis tissue constituents in 548 no-to-low drinking youth age 12-21 years at induction into this five-site, National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. Over the 3-4 year longitudinal examination yielding 2043 MRIs, 328 youth remained no/low drinkers while 220 initiated substantial drinking after initial neuroimaging.Results:Normal growth trajectories derived from no/low drinkers indicated that gray matter volumes of lobules V-VI, Crus II, VIIB, and X declined faster with age in male than female youth, whereas white matter volumes in Crus I-II and lobules VIIIA-VIIIB expanded faster in female than male youth; CSF volume expanded faster in most cerebellar regions of male than female youth. Drinkers exhibited accelerated gray matter decline in anterior lobules and vermis, accelerated vermian white matter expansion, and accelerated CSF volumes expansion of anterior lobules relative to youth who remained no/low drinkers. Analyses including both alcohol and marijuana did not support an independent role for marijuana on alcohol effects on cerebellar gray matter trajectories.Conclusions:Alcohol use-related cerebellar growth trajectory differences from normal involved anterior lobules and vermis of youth who initiated substantial drinking. These regions are commonly affected in alcohol-dependent adults, raising the possibility that cerebellar structures affected with youthful drinking may be vulnerable to age-alcohol interactions in later adulthood.
Importance Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, a... more Importance Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood. Objective To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents. Design, Setting, and Participants This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking. Exposures Self-reported alcohol consumption in the past year summarized by categorical drinking levels. Main Outcomes and Measures Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope. Results Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154 = -2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156 = -0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152 = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence. Conclusions and Relevance This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.
IntroductionIn adolescents, the relationship between alcohol-related blackouts (ARBs) and distinc... more IntroductionIn adolescents, the relationship between alcohol-related blackouts (ARBs) and distinct cognitive changes lasting beyond intoxication is unclear. We examined ARBs as a predictor of persistent changes in the development of learning, memory, and executive function in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study.MethodsDescriptive analyses of the NCANDA sample (N = 831, 50.9% female, 12–21 years at baseline) identified ARB patterns within participants with an ARB history (n = 106). Latent growth curve modeling evaluated ARB-related performance changes on four neuropsychological measures across five years, excluding baseline data to reduce the magnitude of practice effects over time (n = 790). Measures included the Penn Conditional Exclusion Test (PCET), Penn Letter N-back Test (PLBT), Penn Facial Memory Test immediate (PFMTi), and delayed (PFMTd) recognition trials, and the Rey Complex Figure Test copy (RCFTc), immed...
Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-relate... more Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-related economic impacts. We utilized the longitudinal Adolescent Brain Cognitive Development Study to understand how family- and neighborhood-level socioeconomic disadvantage relate to disease burden, family communication, and preventative responses to the pandemic in over 6,000 youth-caregiver dyads. Data were collected at three timepoints (May–August 2020). Here, we show that both family- and neighborhood-level disadvantage were associated with caregivers' reports of greater family COVID-19 disease burden, less perceived exposure risk, more frequent caregiver-youth conversations about COVID-19 risk/prevention and reassurance, and greater youth preventative behaviors. Families with more socioeconomic disadvantage may be adaptively incorporating more protective strategies to reduce emotional distress and likelihood of COVID-19 infection. The results highlight the importance of caregiver-y...
The age- and time-dependent effects of binge drinking on adolescent brain development have not be... more The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan–Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results o...
The novel coronavirus pandemic that emerged in late 2019 (COVID-19) has created challenges not pr... more The novel coronavirus pandemic that emerged in late 2019 (COVID-19) has created challenges not previously experienced in human research. This paper discusses two large-scale NIH-funded multi-site longitudinal studies of adolescents and young adults – the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) and the Adolescent Brain Cognitive Development (ABCD) Study – and valuable approaches to learn about adaptive processes for conducting developmentally sensitive research with neuroimaging and neurocognitive testing across consortia during a global pandemic. We focus on challenges experienced during the pandemic and modifications that may guide other projects, such as implementing adapted protocols that protect the safety of participants and research staff, and addressing assessment challenges through the use of strategies such as remote and mobile assessments. Given the pandemic’s disproportionate impacts on participants typically underrepresented in researc...
The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the ef... more The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical deve...
Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can m... more 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 multifactor...
Alcohol and cannabis use are highly prevalent among adolescents and associated with negative cons... more Alcohol and cannabis use are highly prevalent among adolescents and associated with negative consequences. Understanding motivations behind substance use in youth is important for informing prevention and intervention efforts. The present study aims to examine negative reinforcement principles of substance use among adolescent cannabis and alcohol users by pairing a cue reactivity paradigm with an aversive interoceptive stimulus. Adolescents (ages 15–17), classified as controls (CTL; n = 18), cannabis and/or alcohol experimenters (CAN+ALC-EXP; n = 16), or individuals meeting clinical criteria for cannabis and/or alcohol use disorder (CAN+ALC-SUD; n = 13) underwent functional magnetic resonance imaging during which they experienced an aversive interoceptive probe delivered via breathing load while simultaneously performing a cue reactivity paradigm. Participants also provided self-report ratings of how their substance use is positively or negatively reinforced. While experiencing the...
Biological psychiatry. Cognitive neuroscience and neuroimaging, Jan 21, 2018
Occasional recreational stimulant (amphetamine and cocaine) use is an important public health pro... more Occasional recreational stimulant (amphetamine and cocaine) use is an important public health problem among young adults because 16% of those who experiment develop stimulant use disorder. This study aimed to determine whether behavioral and/or neural processing measures can forecast the transition from occasional to problematic stimulant use. Occasional stimulant users completed a Risky Gains Task during functional magnetic resonance imaging and were followed up 3 years later. Categorical analyses tested whether blood oxygen level-dependent (BOLD) responses differentiated occasional stimulant users who became problem stimulant users (n = 35) from those who desisted from stimulant use (n = 75) at follow-up. Dimensional analyses (regardless of problem stimulant user or desisted stimulant use status; n = 144) tested whether BOLD responses predicted baseline and follow-up stimulant and marijuana use. Categorical results indicated that relative to those who desisted from stimulant use, ...
Objective:The cerebellum is a target of alcoholism-related brain damage in adults. Yet no study h... more Objective:The cerebellum is a target of alcoholism-related brain damage in adults. Yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking.Method:MRI tracked developmental volume trajectories of 10 cerebellar lobule and vermis tissue constituents in 548 no-to-low drinking youth age 12-21 years at induction into this five-site, National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. Over the 3-4 year longitudinal examination yielding 2043 MRIs, 328 youth remained no/low drinkers while 220 initiated substantial drinking after initial neuroimaging.Results:Normal growth trajectories derived from no/low drinkers indicated that gray matter volumes of lobules V-VI, Crus II, VIIB, and X declined faster with age in male than female youth, whereas white matter volumes in Crus I-II and lobules VIIIA-VIIIB expanded faster in female than male youth; CSF volume expanded faster in most cerebellar regions of male than female youth. Drinkers exhibited accelerated gray matter decline in anterior lobules and vermis, accelerated vermian white matter expansion, and accelerated CSF volumes expansion of anterior lobules relative to youth who remained no/low drinkers. Analyses including both alcohol and marijuana did not support an independent role for marijuana on alcohol effects on cerebellar gray matter trajectories.Conclusions:Alcohol use-related cerebellar growth trajectory differences from normal involved anterior lobules and vermis of youth who initiated substantial drinking. These regions are commonly affected in alcohol-dependent adults, raising the possibility that cerebellar structures affected with youthful drinking may be vulnerable to age-alcohol interactions in later adulthood.
Importance Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, a... more Importance Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood. Objective To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents. Design, Setting, and Participants This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking. Exposures Self-reported alcohol consumption in the past year summarized by categorical drinking levels. Main Outcomes and Measures Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope. Results Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154 = -2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156 = -0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152 = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence. Conclusions and Relevance This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.
IntroductionIn adolescents, the relationship between alcohol-related blackouts (ARBs) and distinc... more IntroductionIn adolescents, the relationship between alcohol-related blackouts (ARBs) and distinct cognitive changes lasting beyond intoxication is unclear. We examined ARBs as a predictor of persistent changes in the development of learning, memory, and executive function in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study.MethodsDescriptive analyses of the NCANDA sample (N = 831, 50.9% female, 12–21 years at baseline) identified ARB patterns within participants with an ARB history (n = 106). Latent growth curve modeling evaluated ARB-related performance changes on four neuropsychological measures across five years, excluding baseline data to reduce the magnitude of practice effects over time (n = 790). Measures included the Penn Conditional Exclusion Test (PCET), Penn Letter N-back Test (PLBT), Penn Facial Memory Test immediate (PFMTi), and delayed (PFMTd) recognition trials, and the Rey Complex Figure Test copy (RCFTc), immed...
Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-relate... more Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-related economic impacts. We utilized the longitudinal Adolescent Brain Cognitive Development Study to understand how family- and neighborhood-level socioeconomic disadvantage relate to disease burden, family communication, and preventative responses to the pandemic in over 6,000 youth-caregiver dyads. Data were collected at three timepoints (May–August 2020). Here, we show that both family- and neighborhood-level disadvantage were associated with caregivers' reports of greater family COVID-19 disease burden, less perceived exposure risk, more frequent caregiver-youth conversations about COVID-19 risk/prevention and reassurance, and greater youth preventative behaviors. Families with more socioeconomic disadvantage may be adaptively incorporating more protective strategies to reduce emotional distress and likelihood of COVID-19 infection. The results highlight the importance of caregiver-y...
The age- and time-dependent effects of binge drinking on adolescent brain development have not be... more The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan–Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results o...
The novel coronavirus pandemic that emerged in late 2019 (COVID-19) has created challenges not pr... more The novel coronavirus pandemic that emerged in late 2019 (COVID-19) has created challenges not previously experienced in human research. This paper discusses two large-scale NIH-funded multi-site longitudinal studies of adolescents and young adults – the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) and the Adolescent Brain Cognitive Development (ABCD) Study – and valuable approaches to learn about adaptive processes for conducting developmentally sensitive research with neuroimaging and neurocognitive testing across consortia during a global pandemic. We focus on challenges experienced during the pandemic and modifications that may guide other projects, such as implementing adapted protocols that protect the safety of participants and research staff, and addressing assessment challenges through the use of strategies such as remote and mobile assessments. Given the pandemic’s disproportionate impacts on participants typically underrepresented in researc...
The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the ef... more The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical deve...
Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can m... more 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 multifactor...
Alcohol and cannabis use are highly prevalent among adolescents and associated with negative cons... more Alcohol and cannabis use are highly prevalent among adolescents and associated with negative consequences. Understanding motivations behind substance use in youth is important for informing prevention and intervention efforts. The present study aims to examine negative reinforcement principles of substance use among adolescent cannabis and alcohol users by pairing a cue reactivity paradigm with an aversive interoceptive stimulus. Adolescents (ages 15–17), classified as controls (CTL; n = 18), cannabis and/or alcohol experimenters (CAN+ALC-EXP; n = 16), or individuals meeting clinical criteria for cannabis and/or alcohol use disorder (CAN+ALC-SUD; n = 13) underwent functional magnetic resonance imaging during which they experienced an aversive interoceptive probe delivered via breathing load while simultaneously performing a cue reactivity paradigm. Participants also provided self-report ratings of how their substance use is positively or negatively reinforced. While experiencing the...
Biological psychiatry. Cognitive neuroscience and neuroimaging, Jan 21, 2018
Occasional recreational stimulant (amphetamine and cocaine) use is an important public health pro... more Occasional recreational stimulant (amphetamine and cocaine) use is an important public health problem among young adults because 16% of those who experiment develop stimulant use disorder. This study aimed to determine whether behavioral and/or neural processing measures can forecast the transition from occasional to problematic stimulant use. Occasional stimulant users completed a Risky Gains Task during functional magnetic resonance imaging and were followed up 3 years later. Categorical analyses tested whether blood oxygen level-dependent (BOLD) responses differentiated occasional stimulant users who became problem stimulant users (n = 35) from those who desisted from stimulant use (n = 75) at follow-up. Dimensional analyses (regardless of problem stimulant user or desisted stimulant use status; n = 144) tested whether BOLD responses predicted baseline and follow-up stimulant and marijuana use. Categorical results indicated that relative to those who desisted from stimulant use, ...
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