Commentary: Improving the Effectiveness and Utility of the Helping to End Addiction Long-Term (HEAL) Prevention Cooperative: A Full Translational Framework.

The Helping to End Addiction Long-term (HEAL) Prevention Collaborative (HPC) is designed to expedite the development of programs aimed at preventing opioid misuse and opioid use disorder (OUD) in older adolescents and young adults (ages 16-30). Funded by the National Institutes of Health Office of the Director (ODP-NIH), the HPC includes ten outcome studies that focus on distinct interventions to determine their effectiveness and real-world applicability. Also included is a coordinating center at RTI International that supports the individual projects. This commentary highlights the scientific and practical significance of this cooperative and its promise for facilitating the production and implementation of successful interventions. Attributes such as novel program designs, advanced methodologies, addressing unique characteristics of diverse populations, and real-time analysis of data and costs make this cooperative highly innovative. We note, however, that papers in this Supplemental Issue did not specifically address the persistent need to obtain stronger effect sizes than those achieved to date. Existing data captured earlier in development (< 16 years of age) are uncovering interactive neurocognitive and social-contextual mechanisms underlying the phenomena we wish to prevent. HPC projects could be guided by this information to incorporate developmentally appropriate measures of mechanisms shown previously to be influential in targeted outcomes and determine how they are impacted by specific components of their interventions. This mechanistic information can provide a roadmap for constructing interventions that are more precision-based and, thus, more likely to yield greater benefits for a larger number of recipients. Furthermore, an understanding of underlying mechanism(s) promises to shed light on the sources of heterogeneity in outcomes for further intervention refinement. It is quite possible, if not probable, that meaningful measures of underlying processes will reveal subtypes-some with very high effect sizes and others that are much lower-directly enabling program refinements to more directly target mechanisms that portend and explain less favorable outcomes. Described herein is a full-spectrum translational approach which promises to significantly boost effect sizes, a key objective that should be reached prior to scaling.

Implementing Adolescent Wellbeing and Health Programs in Schools: Insights from a Mixed Methods and Multiple Informant Study.

Determining the factors that influence implementation of school-based wellbeing and health programs is essential for achieving desired program effects. Using a convergent mixed-methods, multiple informant design, this study considered factors that influence implementation of health programs for ninth grade students and in what ways implementation is differentially perceived by multiple informants (i.e., participants, instructors, and independent observers). Two types of programs-mindfulness and health education-were implemented with ninth graders (N = 70) in three schools situated in low-resourced urban neighborhoods. Study outcomes were derived from four data sources: (1) focus group participants (N = 45); (2) program instructor fidelity ratings; (3) independent observer fidelity ratings and notes; and (4) instructor open-ended session responses. Using thematic and mixed methods integration analyses, we identified themes related to implementation promoting or challenging factors. Theme names differed when data sources were separately analyzed by informant. Mixed methods integration analysis indicated that four themes were common across all informant groups: (1) competent, attentive, and engaging instructors are essential; (2) programs should involve interactive components (e.g., physical activities, applied learning opportunities); (3) adequate time for program delivery is key for student exposure and engagement; and (4) students' availability and preferences should guide program scheduling. A fifth theme, unique to instructor and observer perspectives, was that program implementation was negatively impacted by distractions from multiple sources, including instructors, students, and settings. Recommendations from students, instructors, and observers for implementation optimization are discussed.

Normalization of Prevention Principles and Practices to Reduce Substance Use Disorders Through an Integrated Dissemination and Implementation Framework.

Major research breakthroughs over the past 30 years in the field of substance use prevention have served to: (1) enhance understanding of pharmacological effects on the central and peripheral nervous systems and the health and social consequences of use of psychoactive substances, particularly for children and adolescents; (2) delineate the processes that increase vulnerability to or protect from initiation of substance use and progression to substance use disorders (SUDs) and, based on this understanding, (3) develop effective strategies and practices to prevent the initiation and escalation of substance use. The challenge we now face as a field is to "normalize" what we have learned from this research so that it is incorporated into the work of those involved in supporting, planning, and delivering prevention programming to populations around the world, is integrated into health and social service systems, and helps to shape public policies. But we wish to go further, to incorporate these effective prevention practices into everyday life and the mind-sets of the public, particularly parents and educators. This paper reviews the advances that have been made in the field of prevention and presents a framework and recommendations to achieve these objectives generated during several meetings of prevention and implementation science researchers sponsored by the International Consortium of Universities for Drug Demand Reduction (ICUDDR) that guides a roadmap to achieve "normalization."

The moderating role of socioeconomic status on level of responsibility, executive functioning, and cortical thinning during adolescence.

Brain development is exquisitely sensitive to psychosocial experiences, with implications for neurodevelopmental trajectories, for better or worse. The premise of this investigation was that the level of responsibility in adolescence may relate to brain structure and higher-order cognitive functions. In a sample of 108 adolescents, we focused on cortical thickness (using FreeSurfer) as an indicator of neurodevelopment in regions previously implicated in executive functioning (EF) and examined performance on an EF task outside of the scanner, in the context of level of responsibility. We further investigated whether socioeconomic status (SES) and family stress moderated the relationship between responsibility and brain structure or EF. Findings revealed that greater responsibility was related to thinner left precuneus and right middle frontal cortex. In lower SES adolescents, greater responsibility predicted thinner left precuneus and right middle frontal cortex, which have been consistently implicated in EF. Higher SES adolescents did not show structural differences related to responsibility, however, they did exhibit better EF performance. It may be that circumstances surrounding the need for greater responsibility in lower SES households are detrimental to neurodevelopment compared to higher SES households. Alternatively, responsibility may act as a protective factor that bolsters cortical thinning in regions related to EF.

Relationship between whole blood omega-3 fatty acid levels and dorsal cingulate gray matter volume: Sex differences and implications for impulse control.

During adolescence, the prefrontal cortex (PFC) undergoes substantial structural development, including cortical thinning, a process associated with improvements in behavioral control. The cingulate cortex is among the regions recruited in response inhibition and mounting evidence suggests cingulate function may be sensitive to availability of an essential dietary nutrient, omega-3 fatty acids (N3; i.e. EPA + DHA). Our primary aim was to investigate the relationship between a biomarker of omega-3 fatty acids -- percent of whole blood fatty acids as EPA + DHA (N3 Index) -- and cingulate morphology, in typically developing adolescent males (n = 29) and females (n = 33). Voxel-based morphometry (VBM) was used to quantify gray matter volume (GMV) in the dorsal region of the cingulate (dCC). Impulse control was assessed via caregiver report (BRIEF) and Go/No-Go task performance. We predicted that greater N3 Index in adolescents would be associated with less dCC GMV and better impulse control. Results revealed that N3 Index was inversely related to GMV in males, but not in females. Furthermore, males with less right dCC GMV exhibited better caregiver-rated impulse control. A simple mediation model revealed that, in males, N3 Index may indirectly impact impulse control through its association with right dCC GMV. Findings suggest a sex-specific link between levels of N3 and dCC structural development, with adolescent males more impacted by lower N3 levels than females. Identifying factors such as omega-3 fatty acid levels, which may modulate the neurodevelopment of response inhibition, is critical for understanding typical and atypical developmental trajectories associated with this core executive function.

Personalizing and Optimizing Preventive Intervention Models via a Translational Neuroscience Framework.

A new generation of research, building upon developmental psychopathology (Luthar et al. 1997; Luthar et al. (Child Development, 71, 543-562, 2000)), provides evidence that individual differences in risk for behavioral health problems result from intrapersonal and environmental modulation of neurophysiologic and genetic substrates. This transdisciplinary model suggests that, in any given individual, the number of genetic variants implicated in high-risk behavior and the way in which they are assorted and ultimately suppressed or activated in the brain by experiential and contextual factors help to explain behavioral orientations. Implications are that behavioral health problems can be amplified or reduced based on characteristics of an individual and socio-contextual influences on those characteristics. This emerging research has extraordinary implications for the design of prevention programs that more precisely target the malleable mechanisms that underlie behavioral health problems and, hence, more effectively prevent behavioral problems and promote resilience. A detailed, theory-driven examination of all evidence-based interventions is called for to identify the active ingredients that specifically impact these underlying mechanisms. Such an approach will enhance the ability of preventive interventions to achieve effect sizes indicative of beneficial impacts for a greater number of recipients. This paper presents the significant implications of this collective knowledge base for the next generation of precision-based, prevention-focused personalized interventions.

Short-Term Intervention Effects of the PATHS Curriculum in Young Low-Income Children: Capitalizing on Plasticity.

Deficits in behavioral and cognitive regulation are prevalent in children reared in poverty relative to more affluent children due to the effects of adverse conditions on the developmental underpinnings of these skills. Despite evidence to suggest that these emergent processes are susceptible to environmental inputs, research documenting short-term intervention program influences on these regulatory domains in young impoverished children is limited. We sought to determine the proximal effects of a universal school-based intervention (the PATHS Curriculum) on social, emotional, relational, and cognitive outcomes in urban poor kindergarten children. Four schools in high-poverty neighborhoods with similar demographic characteristics were randomly assigned to either PATHS or an attentional control. Teacher-reported measures of behavior (e.g., attention, concentration, aggression), peer nominations (e.g., likability, aggression, acceptance), and tasks gauging inhibitory control were administered in the fall of kindergarten and again in the spring after one academic year (about 6 months) of PATHS. Children who received PATHS exhibited significantly greater improvements than control students across all teacher-rated behavioral measures of social competence (i.e., emotion regulation, prosocial behavior, peer relations) and behavioral problems (i.e., aggression, internalizing behaviors, impulsivity and hyperactivity) at post-test as well as improvements in motor inhibition. This line of research constitutes an important frontier for prevention research given the implications for improving ultimate outcomes for otherwise disadvantaged children.

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.

A National Strategy for Preventing Substance and Opioid Use Disorders Through Evidence-Based Prevention Programming that Fosters Healthy Outcomes in Our Youth.

The recently released National Drug Control Strategy (2022) from the White House Office of National Drug Control Policy (ONDCP) lays out a comprehensive plan to, not only enhance access to treatment and increase harm reduction strategies, but also increase implementation of evidence-based prevention programming at the community level. Furthermore, the Strategy provides a framework for enhancing our national data systems to inform policy and to evaluate all components of the plan. However, not only are there several missing components to the Strategy that would assure its success, but there is a lack of structure to support a national comprehensive service delivery system that is informed by epidemiological data, and trains and credentials those delivering evidence-based prevention, treatment, and harm reduction/public health interventions within community settings. This paper provides recommendations for the establishment of such a structure with an emphasis on prevention. Systematically addressing conditions known to increase liability for behavioral problems among vulnerable populations and building supportive environments are strategies consistently found to avert trajectories away from substance use in general and substance use disorders (SUD) in particular. Investments in this approach are expected to result in significantly lower rates of SUD in current and subsequent generations of youth and, therefore, will reduce the burden on our communities in terms of lowered social and health systems involvement, treatment needs, and productivity. A national strategy, based on strong scientific evidence, is presented to implement public health policies and prevention services. These strategies work by improving child development, supporting families, enhancing school experiences, and cultivating positive environmental conditions.

Science for policy to protect children in cyberspace.

Cross-disciplinary partnerships are needed to formulate policies that account for developmental vulnerabilities.

Effects of OPRM1 and DRD2 on brain structure in drug-naïve adolescents: Genetic and neural vulnerabilities to substance use.

Genetic variants in the opioid receptor mu 1 (OPRM1) and dopamine receptor d2 (DRD2) genes are implicated in behavioral phenotypes related to substance use disorders (SUD). Despite associations among OPRM1 (rs179971) and DRD2 (rs6277) genes and structural alterations in neural reward pathways implicated in SUDs, little is known about the contribution of risk-related gene variants to structural neurodevelopment. In a 3-year longitudinal study of initially SU-naïve adolescents (N = 129; 70 females; 11-14 years old), participants underwent an MRI structural scan at baseline and provided genetic assays for OPRM1 and DRD2 with SU behavior assessed during follow-up visits. Baseline differences in key reward-related brain regions (i.e., bilateral caudate and cingulate cortex) were detected in those with genetic liability for SU in OPRM1 who went onto engage in SU at subsequent waves of data collection. In addition, main effects of OPRM1, DRD2, and SU were related to variability in structure of the putamen, anterior cingulate, and nucleus accumbens, respectively. These data provide preliminary evidence that genetic risk factors interact with future SU to confer structural variability prior to SU in regions commonly implicated in risk for SU and the development of SUDs.

Baseline brain and behavioral factors distinguish adolescent substance initiators and non-initiators at follow-up.

Background: Earlier substance use (SU) initiation is associated with greater risk for the development of SU disorders (SUDs), while delays in SU initiation are associated with a diminished risk for SUDs. Thus, identifying brain and behavioral factors that are markers of enhanced risk for earlier SU has major public health import. Heightened reward-sensitivity and risk-taking are two factors that confer risk for earlier SU. Materials and methods: We characterized neural and behavioral factors associated with reward-sensitivity and risk-taking in substance-naïve adolescents (N = 70; 11.1-14.0 years), examining whether these factors differed as a function of subsequent SU initiation at 18- and 36-months follow-up. Adolescents completed a reward-related decision-making task while undergoing functional MRI. Measures of reward sensitivity (Behavioral Inhibition System-Behavioral Approach System; BIS-BAS), impulsive decision-making (delay discounting task), and SUD risk [Drug Use Screening Inventory, Revised (DUSI-R)] were collected. These metrics were compared for youth who did [Substance Initiators (SI); n = 27] and did not [Substance Non-initiators (SN); n = 43] initiate SU at follow-up. Results: While SI and SN youth showed similar task-based risk-taking behavior, SI youth showed more variable patterns of activation in left insular cortex during high-risk selections, and left anterior cingulate cortex in response to rewarded outcomes. Groups displayed similar discounting behavior. SI participants scored higher on the DUSI-R and the BAS sub-scale. Conclusion: Activation patterns in the insula and anterior cingulate cortex may serve as a biomarker for earlier SU initiation. Importantly, these brain regions are implicated in the development and experience of SUDs, suggesting differences in these regions prior to substance exposure.

Introducing an adolescent cognitive maturity index.

Children show substantial variation in the rate of physical, cognitive, and social maturation as they traverse adolescence and enter adulthood. Differences in developmental paths are thought to underlie individual differences in later life outcomes, however, there remains a lack of consensus on the normative trajectory of cognitive maturation in adolescence. To address this problem, we derive a Cognitive Maturity Index (CMI), to estimate the difference between chronological and cognitive age predicted with latent factor estimates of inhibitory control, risky decision-making and emotional processing measured with standard neuropsychological instruments. One hundred and forty-one children from the Adolescent Development Study (ADS) were followed longitudinally across three time points from ages 11-14, 13-16, and 14-18. Age prediction with latent factor estimates of cognitive skills approximated age within ±10 months (r = 0.71). Males in advanced puberty displayed lower cognitive maturity relative to peers of the same age; manifesting as weaker inhibitory control, greater risk-taking, desensitization to negative affect, and poor recognition of positive affect.

Latent Class Analysis of Individual-Level Characteristics Predictive of Intervention Outcomes in Urban Male Adolescents.

Preventive intervention research dictates that new techniques are needed to elucidate what types of interventions work best for whom to prevent behavioral problems. The current investigation applies a latent class modeling structure to identify the constellation of characteristics-or profile-in urban male adolescents (n = 125, aged 15) that interrelatedly predict responses to a brief administration of an evidence-based program, Positive Adolescent Choices Training (PACT). Individual-level characteristics were selected as predictors on the basis of their association with risk behaviors and their implication in intervention outcomes (e.g., mental health, stress exposure, temperament, cognitive function, stress reactivity and emotion perception). Outcome measures included virtual reality vignettes and questionnaire-style role play scenarios to gauge orientations around aggressive conflict resolution, communication, emotional control, beliefs supporting aggression and hostility. A three-class model was found to best fit the data: "NORMative" (NORM), with relatively low symptomatology; "Mental Health" problems (MH-I) with elevated internalizing symptoms; and "Mental Health-E + Cognitive Deficit" (MH-E + Cog) with elevated mental health symptoms paired with cognitive decrements. The NORM class had positive PACT effects for communication, conflict resolution, and aggressive beliefs. Moderation was evidenced by lack of positive PACT effects for the MH-I and MH-E + Cog groups. Also, PACT classes with MH issues showed marginally significant worsening of aggressive beliefs compared to control students in the same class. Results suggest that a latent class model may identify "signatures" or profiles of traits, experiences and other influences that collectively-and more realistically-predict variable intervention outcomes with implications for more effectively targeting interventions than singular factors.

The risk of assimilating? Alcohol use among immigrant and U.S.-born Mexican youth.

Rising rates of substance use among Hispanic youth, coupled with substantial growth of this minority group, merit grounds for concern. The process of assimilation is frequently examined in studies of Hispanic substance use and has been cited as a reason for higher rates of substance use by U.S.-born Hispanics, compared to their foreign-born peers. However, many previous studies use individual or unidimensional measures of assimilation, when this term is multifaceted, representing different concepts. The current study addresses this gap by testing the longitudinal effect of different assimilation processes (acculturation as well as structural, spatial, and straight-line assimilation), while simultaneously controlling for important familial and social risk and protective factors on the likelihood of alcohol use among U.S.-born Mexican and Mexican immigrant youth. Results indicate that, although alcohol use is higher among immigrant youth, assimilation measures do not predict alcohol use for immigrants or U.S.-born youth. We conclude that the effects of assimilation may vary by person and place, particularly in ethnic enclaves, and suggest the use of measures that incorporate cultural, personal, social, and environmental factors.

Corrigendum: Neurocognitive Precursors of Substance Misuse Corresponding to Risk, Resistance, and Resilience Pathways: Implications for Prevention Science.

[This corrects the article DOI: 10.3389/fpsyt.2019.00399.].

Characterizing psychiatric symptoms and neurocognitive functioning among substance-naïve early adolescents: Associations with sleep problems.

AIM: Evidence consistently links psychiatric symptoms, reduced neurocognitive functioning (NCF) and sleep problems to the initiation of a wide range of risk behaviours. Less is known, however, about the associations between sleep problems with psychiatric symptoms and NCF among early adolescents yet to engage in substance use. METHODS: The present study examined baseline data from an ongoing prospective study of 529 youth aged 10-12 years who completed a battery of instruments measuring symptom counts for four psychiatric disorders, performance on six tests of NCF and five types of sleep behaviour on week days. We used latent class analysis to classify the 473 substance-naïve youth into subtypes characterized by probabilistic patterns of psychiatric symptoms and poorer NCF. RESULTS: Four subtypes emerged: normative (24% of the sample); nonspecific mental health symptoms (27%); lower neurocognitive function (24%) and comorbid psychiatric symptoms and lower neurocognitive function (25%). In a multivariable latent regression model, three or more sleep arousals per night, sleep phase of two or more hours and sleep latency of 20 minutes or more were significantly associated with the two classes having higher symptom counts. Lack of family support was significantly associated with the two classes having lower neurocognitive function and comorbid psychiatric symptoms. CONCLUSIONS: The youth subtypes in this study provide an important baseline characterization to subsequently understand how these neuropsychiatric relationships may change when substance use and other risk behaviours develop during adolescence. Implications for preventing and treating sleep problems associated with psychiatric comorbidity and neurocognitive dysfunctions are discussed.

Social Emotional Learning Program Boosts Early Social and Behavioral Skills in Low-Income Urban Children.

Social emotional learning (SEL) programs are increasingly being implemented in elementary schools to facilitate development of social competencies, decision-making skills, empathy, and emotion regulation and, in effect, prevent poor outcomes such as school failure, conduct problems, and eventual substance abuse. SEL programs are designed to foster these abilities in children with a wide range of behavioral, social, and learning needs in the classroom, including children who are economically disadvantaged. In a previous study of kindergartners residing in a high-poverty community (N = 327 at baseline), we observed significant behavioral improvements in children receiving an SEL program-The PATHS® curriculum (PATHS)-relative to an active control condition within one school year. The present investigation sought to determine whether these improvements were sustained over the course of two school years with intervention and an additional year when intervention was no longer provided. Further, using multilevel models, we examined whether baseline measures of neurocognition and stress physiology-known to be adversely impacted by poverty-moderated heterogeneous outcomes. Finally, a preliminary linear regression analysis explored whether neurocognition and physiological stress reactivity (heart rate variability, HRV) predict change in outcomes postintervention. Results confirmed that students who received PATHS sustained significant behavioral improvements over time. These effects occurred for the full sample, irrespective of putative baseline moderators, suggesting that children in high-risk environments may benefit from SEL interventions irrespective of baseline cognitive functioning as a function of overall substantial need. Of interest is that our exploratory analysis of change from waves three to four after the intervention concluded brought to light possible moderation by baseline physiology. Should subsequent studies confirm this finding, one plausible explanation may be that, when an intervention providing protective effects is withdrawn, children with higher HRV may not be able to regulate physiological stress responses to environmental challenges, leading to an uptick in maladaptive behaviors. In reverse, children with lower HRV-generally associated with poorer emotion regulation-may incur relatively greater gains in behavioral improvement due to lesser sensitivity to the environment, enabling them to continue to accrue benefits. Results are discussed in the context of possible pathways that may be relevant to understanding the special needs of children reared in very low-income, high-stress neighborhoods.