Individual-, peer-, and parent-level substance use-related factors among 9- and 10-year-olds from the ABCD Study: Prevalence rates and sociodemographic differences.

Background: Although a relatively large body of research has identified multiple factors associated with adolescent substance use, less is known about earlier substance-related factors during preadolescence, including curiosity to use substances. The present study examined individual-, peer-, and parent-level domains pertaining to substance use and how these domains vary by sociodemographic subgroups and substance type. Methods: Participants were 11,864 9- and 10-year-olds from the baseline sample of the Adolescent Brain Cognitive Development (ABCD) Study. Youth-reported measures were curiosity to use substances and perceived peer substance use. Parent-reported measures were availability of and rules about substances. Generalized logistic mixed models (GLMM) were used to compare these measures across alcohol, nicotine, and marijuana and across sociodemographic subgroupings (sex, race/ethnicity, household income, and family history of alcohol problems). GLMM was then used to examine predictors of curiosity to use by substance type. Results: The most striking descriptive differences were found between race/ethnicity and income categories (e.g., positive associations between greater income and greater availability of alcohol). In multivariable analyses, greater curiosity to use alcohol was associated with being male, higher household income, perceived peer alcohol use, and easy alcohol availability; greater curiosity to use nicotine was associated with being male, perceived peer cigarette use, easy availability of cigarettes, and no parental rules about cigarette use. Conclusions: This study identified substance use-related individual-, peer-, and parent-level factors among a diverse, national sample. Findings highlight the importance of considering sociodemographic and substance-specific variability and may help identify risk and protective factors preceding adolescent substance use.

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study.

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics. Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels. Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample. Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

OBJECTIVE: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. METHOD: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. RESULTS: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Childhood adversity, externalizing behavior, and substance use in adolescence: Mediating effects of anterior cingulate cortex activation during inhibitory errors.

Childhood adversity can negatively impact development across various domains, including physical and mental health. Adverse childhood experiences have been linked to aggression and substance use; however, developmental pathways to explain these associations are not well characterized. Understanding early precursors to later problem behavior and substance use can inform preventive interventions. The aim of the current study was to examine neurobiological pathways through which childhood adversity may lead to early adolescent problem behavior and substance use in late adolescence by testing two prospective models. Our first model found that early adolescent externalizing behavior mediates the association between childhood adversity and alcohol, cigarette, and marijuana use in late adolescence. Our second model found that activation in the anterior cingulate cortex (ACC) during an inhibitory control task mediates the association between childhood adversity and early adolescent externalizing behavior, with lower ACC activation associated with higher levels of adversity and more externalizing behavior. Together these findings indicate that the path to substance use in late adolescence from childhood adversity may operate through lower functioning in the ACC related to inhibitory control and externalizing behavior. Early life stressors should be considered an integral component in the etiology and prevention of early and problematic substance use.

Psychosocial and neural indicators of resilience among youth with a family history of substance use disorder.

BACKGROUND: Little is known regarding the combined influence of psychosocial and neural protective mechanisms against substance use. The present study examined the extent to which neuroimaging measures of disinhibition predicted resilience against binge drinking and marijuana use among youth with a family history of substance use disorder (SUD; FH+), accounting for psychosocial measures of behavioral control. METHODS: Participants were 57 FH+ youth from the Michigan Longitudinal Study categorized into resilient and high-risk groups based on patterns of weekly binge drinking and monthly marijuana use during early adulthood. Psychosocial measures of behavioral control (reactive control and externalizing behavior during early and late adolescence) and neural measures of disinhibition (Go/No-Go task and Monetary Incentive Delay Task (MIDT) measured through functional magnetic resonance imaging (fMRI)) were entered sequentially in hierarchical logistic regression models to predict resilient versus high-risk groups. RESULTS: Greater activation in the right dorsolateral prefrontal cortex (DLPFC) during correctly inhibited trials on the Go/No-Go task was a significant predictor of resilience (OR = 2.46, p < 0.05), over and above greater reactive control in early adolescence (OR = 4.96, p < 0.05) and lower externalizing behavior in late adolescence (OR = 0.64, p < 0.05). Neural activation in the ventral striatum associated with reward anticipation during the MIDT was not a significant predictor of resilience. CONCLUSIONS: Brain function in the right DLPFC associated with inhibitory control may be a neural indicator of resilience against elevated substance use among FH+ youth, even after accounting for psychosocial measures of behavioral control.

Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation.

IMPORTANCE: Marijuana use may alter ventral striatal response to reward, which might heighten susceptibility to substance use disorder. Longitudinal research is needed to determine the effects of marijuana use on neural function involved in reward response. OBJECTIVE: To determine whether marijuana use among young adults prospectively affects nucleus accumbens (NAcc) activation during reward anticipation. DESIGN, SETTING, AND PARTICIPANTS: One hundred eight young adults were recruited from the Michigan Longitudinal Study, an ongoing study of youth at high risk for substance use disorder and a contrast sample of control families. Participants underwent 3 consecutive functional magnetic resonance imaging scans at approximate ages of 20 (time 1), 22 (time 2), and 24 (time 3) years. Self-report data on marijuana and other drug use occasions were collected annually since age 11 years. MAIN OUTCOMES AND MEASURES: Cross-lagged models were used to test the association of marijuana use with neural response in the NAcc to reward anticipation during a monetary incentive delay task controlling for sex, age, other substance use, and family history of substance use disorder. RESULTS: Of 108 participants, 39 (36.1%) were female and mean (SD) age at baseline was 20.1 (1.4) years. Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: ß = -0.26, P = .04; time 2 to time 3: ß = -0.25, P = .01). When the cross-lagged model was tested with the inclusion of previous and concurrent cigarette use, the effect of marijuana use from time 2 to time 3 remained significant (ß = -0.29; P = .005) and the effect of cigarette use was nonsignificant. CONCLUSIONS AND RELEVANCE: The findings of this study indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of nondrug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase the risk for continued drug use and later addiction.

Executive function in chronic pain patients and healthy controls: different cortical activation during response inhibition in fibromyalgia.

UNLABELLED: The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance-based deficits are seen mainly in tests of working memory and executive function. Neural correlates of executive function were investigated in 18 FM patients and 14 age-matched healthy controls during a simple Go/No-Go task (response inhibition) while they underwent functional magnetic resonance imaging (fMRI). Performance was not different between FM and healthy control, in either reaction time or accuracy. However, fMRI revealed that FM patients had lower activation in the right premotor cortex, supplementary motor area, midcingulate cortex, putamen and, after controlling for anxiety, in the right insular cortex and right inferior frontal gyrus. A hyperactivation in FM patients was seen in the right inferior temporal gyrus/fusiform gyrus. Despite the same reaction times and accuracy, FM patients show less brain activation in cortical structures in the inhibition network (specifically in areas involved in response selection/motor preparation) and the attention network along with increased activation in brain areas not normally part of the inhibition network. We hypothesize that response inhibition and pain perception may rely on partially overlapping networks, and that in chronic pain patients, resources taken up by pain processing may not be available for executive functioning tasks such as response inhibition. Compensatory cortical plasticity may be required to achieve performance on a par with control groups. PERSPECTIVE: Neural activation (fMRI) during response inhibition was measured in fibromyalgia patients and controls. FM patients show lower activation in the inhibition and attention networks and increased activation in other areas. Inhibition and pain perception may use overlapping networks: resources taken up by pain processing may be unavailable for other processes.

Smoking modulation of mu-opioid and dopamine D2 receptor-mediated neurotransmission in humans.

This is a pilot examination of the hypothesis that some of the effects of smoking cigarettes in humans are mediated through nicotine activation of opioid and dopamine (DA) neurotransmission. Neuroimaging was performed using positron emission tomography and the radiotracers [11C]carfentanil and [11C]raclopride, labeling mu-opioid and DA D2 receptors, respectively. Six healthy male smokers were abstinent overnight. After radiotracer administration, subjects smoked two denicotinized cigarettes, followed 45 min later by two average nicotine cigarettes. Dynamic data were acquired over 90 min, and transformed into parametric maps of receptor availability in vivo (binding potential, BP), corresponding to low and high nicotine smoking periods and analyzed on a voxel-by-voxel basis using SPM'99 and correction for multiple comparisons. Significant activation of mu-opioid receptor-mediated neurotransmission from denicotinized to average nicotine conditions was observed in the right anterior cingulate cortex. DA D2 neurotransmission was activated in the ventral basal ganglia, correlating with Fagerström scale nicotine dependence scores. Lower mu-opioid receptor BP was also detected during the denicotinized smoking condition in the smoker group, compared to baseline scans in non-smokers, in the cingulate cortex, thalamus, ventral basal ganglia, and amygdala. These reductions were reversed during the average nicotine condition in the thalamus, ventral basal ganglia and amygdala. These data point to both the feasibility of simultaneously examining opioid and DA neurotransmission responses to smoking in humans, as well as to the need to examine non-nicotine aspects of smoking to more fully understand the behavioral effects of this drug.

Regional cerebral blood flow responses to smoking in tobacco smokers after overnight abstinence.

OBJECTIVE: The purpose of the study was to determine the effects of cigarette smoking on brain regional function in a group of chronic smokers by using cerebral blood flow (CBF) measures and positron emission tomography (PET). METHOD: Nineteen tobacco smokers were studied after about 12 hours of smoking abstinence. Regional CBF (rCBF) measures were obtained with PET and [15O]H2O in six consecutive scans. Two average-nicotine-yield (1.0 mg) and one denicotinized (0.08 mg) research cigarettes with similar tar yields (9.5 mg and 9.1 mg, respectively) were smoked in a double-blind design, preceded and followed by baseline scans. The rCBF effects of smoking were compared to baseline measures and between cigarettes, as well as to subjective ratings of craving for cigarettes. RESULTS: Smoking the first cigarette of the day resulted in increases in rCBF in the visual cortex and the cerebellum and reductions in the anterior cingulate, the right hippocampus, and the ventral striatum, including the nucleus accumbens. Cigarette craving scores correlated with rCBF changes in the dorsal anterior cingulate and right hippocampus. Less pronounced effects were observed with the second cigarette and the denicotinized cigarette. CONCLUSIONS: Smoking affects rCBF not only in areas of the brain rich in nicotinic cholinergic receptors but also in areas implicated in the rewarding effects of drugs of abuse. Furthermore, craving for a cigarette in chronic smokers was correlated with rCBF in the right hippocampus, an area involved in associating environmental cues with drugs, and in the left dorsal anterior cingulate, an area implicated in drug craving and relapse to drug-seeking behavior.