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

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

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\u27s 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

Adolescent alcohol use and fMRI BOLD response : a longitudinal study

Background : Many adolescents engage in heavy alcohol use. From existing literature it is difficult to disentangle whether brain abnormalities are a consequence of heavy drinking, a preexisting risk factor for initiation of alcohol use, or both. Methods: This study uses longitudinal functional magnetic resonance imaging (fMRI) data from 12 to 16 year-olds (N=40) imaged prior to the onset of drinking, then again approximately three years later after half transitioned to heavy drinking (80 total scans). Heavy drinkers and non-users were matched on baseline and follow-up developmental and risk factors. A repeated measures group x time ANOVA on a priori specified regions of interest was conducted to determine if youth who initiated heavy drinking evidenced a change in activation pattern, as compared to youth who remained non- drinkers. Regions showing divergent activation among initiators of heavy drinking were examined for correspondence with neuropsychological measures of VWM and attention among the heavy drinkers (n=20) in regression analyses. Results : As hypothesized, significant group x time interactions were found in the right inferior parietal lobule (cluster size: 810[mu]L, p=.005; [eta]²=.23) and left medial frontal gyrus (cluster size: 1431[mu]L, p=.003; [eta]²=.19). For both interactions, heavy drinkers showed significantly less blood oxygen level dependent (BOLD) response contrast to high relative to low working memory loads at baseline that increased after the onset of heavy drinking, as compared to controls. Contrary to hypotheses, BOLD response contrast and its change over time were not related to follow-up neuropsychological performance. Discussion: Adolescents who initiated heavy drinking had different brain activation compared to non-drinkers prior to the onset of drinking, suggesting brain activation patterns could be a risk factor for future substance use. Over time, adolescent heavy drinkers exhibited less efficient and mature processing of information. While brain activation did not correlate with behavioral measures, continued heavy use during this important developmental period could compromise neural networks. This investigation helps clarify the effect of alcohol use on brain functioning during adolescence, and aids in understanding whether abnormalities in VWM response among adolescent drinkers follow the initiation of alcohol involvement or predate the onset of drinkin