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.

Prevention Science and Health Equity: A Comprehensive Framework for Preventing Health Inequities and Disparities Associated with Race, Ethnicity, and Social Class.

The ultimate goal of our public health system is to reduce the incidence of disability and premature death. Evidence suggests that, by this standard, the USA falls behind most other developed countries largely as a function of disparities in health outcomes among significant portions of the US population. We present a framework for addressing these disparities that attributes them, not simply to differences in the behavioral and physical risk factors, but to social, environmental, and structural inequities such as poverty, discrimination, toxic physical setting, and the marketing of harmful products. These inequities result from de facto and instituted public policies. An analysis of the NIH research portfolio indicates a relative lack of investment in experimental evaluations of preventive interventions-especially studies targeting disadvantaged populations. Moreover, experimental research on reducing social inequities is almost entirely lacking. A line of research focusing on the drivers of inequities and their dissolution must include experimental evaluation of strategies for getting policies adopted that will reduce inequities. In conclusion, a summary is provided of the types of research that are needed and the challenges involved in conducting the experimental research that is essential for reducing inequities and disparities and, in turn, prolonging life.

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.

The Pivotal Role of Prevention Science in This Syndemic.

Never before has the value of prevention science become so apparent to the populace, particularly in simultaneous fashion across all nations. A general understanding of what prevention represents in true form has lagged well behind the science and, in fact, few outside of the field recognize that there is actually a significant body of research that undergirds preventative practices, programs and policies. The current pandemic and the uneven impacts on underserved and marginalized populations has highlighted the need for proactive approaches to prevent underlying conditions that increase risk for infection, worsen the wide ranging harms from the virus, and significantly exacerbate disparities that characterize many nations. To ensure uptake of the science by end-users (e.g., community stakeholders, practitioners, policymakers), who operate the levers that determine whether resources and services are distributed equitably across societies' sectors, prevention scientists have a unique and powerful role to play. This commentary on the special issue, focused on the "culture of prevention," considers the broader issues covered in the set of original articles in light of the ongoing COVID-19 pandemic. Toward that end, I also outline two interrelated "calls to action" for prevention scientists. The first call is to concertedly apply a race equity lens to all aspects of our research, a need that is particularly critical given that our field is inherently actionable and, as such, evidence amassed has potential to equalize the playing field for disadvantaged and marginalized groups. The second acknowledges the need for prevention scientists to learn how to effectively communicate scientific knowledge to the public and policymakers to compellingly advocate for reforms guided by the science. A powerful, research-backed collective advocacy can effectively sway action of governing bodies in addressing disparities and inequities for constituents who have no voice.

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.

When you go low, I go high: Negative coordination of physiological synchrony among parents and children.

The parent-child relationship is an important context for children's emotional development. The current study assessed 43 parent-child dyads while watching a positive film clip and a negative film clip, in order to examine whether partner's physiological reactivity demonstrated dyadic synchrony, and whether this was associated with children's prosocial empathy. Respiratory sinus arrhythmia was measured in both caretakers and children (ages 9-14) and a continuous time series was estimated in order to maximize temporal resolution of physiological dynamics. Dyads varied in both the magnitude and direction of synchrony, with correlation coefficients ranging from moderately negative; r = -.44 (increases in one partner correspond to decreases in the other), to moderately positive; r = .55 (increases in one partner correspond to increases in the other). For both conditions, negative synchrony was correlated with higher child-reported empathy. For the negative mood condition, this effect was moderated by caretaker's emotional acceptance such that positive synchrony was associated with lower levels of empathy among dyads in which caretaker emotional acceptance was lower. These results suggest that positive physiological synchrony during a negative mood condition may not be adaptive for children when their caretaker lacks the skills to appropriately socialize their child's emotional development.

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.

Translating Prevention Research for Evidence-Based Policymaking: Results from the Research-to-Policy Collaboration Pilot.

The importance of basing public policy on sound scientific evidence is increasingly being recognized, yet many barriers continue to slow the translation of prevention research into legislative action. This work reports on the feasibility of a model for overcoming these barriers-known as the Research-to-Policy Collaboration (RPC). The RPC employs strategic legislative needs assessments and a rapid response researcher network to accelerate the translation of research findings into usable knowledge for policymakers. Evaluation findings revealed that this model can successfully mobilize prevention scientists, engage legislative offices, connect policymakers and experts in prevention, and elicit congressional requests for evidence on effective prevention strategies. On average, the RPC model costs $3510 to implement per legislative office. The RPC can elicit requests for evidence at an average cost of $444 per request. The implications of this work, opportunities for optimizing project elements, and plans for future work are discussed. Ultimately, this project signals that the use of scientific knowledge of prevention in policymaking can be greatly augmented through strategic investment in translational efforts.

The Promise of Prevention Science for Addressing Intergenerational Poverty.

This paper reviews research suggesting that the prevention of intergenerational poverty will be enhanced if we add evidence-based family and school prevention programs to existing efforts to reduce poverty in order to address the adverse social environments that often accompany poverty. Government policies such as the Earned Income Tax Credit can reduce family poverty, but simply improving the economic stability of the family will not necessarily prevent the development of child and adolescent problems such as academic failure, antisocial behavior, drug abuse, and depression, all of which can undermine future economic wellbeing. We briefly review the evidence linking family poverty to adverse social environments, which can have deleterious effects on children's psychological, behavioral, neurological, and physical development. We then document the value of evidence-based family- and school-based prevention programs in effectively addressing these behavioral, emotional, cognitive, and neurophysiological factors that can put children at risk for continued poverty in adulthood. We also describe three family-based prevention programs that have been found to have a direct effect on families' future economic wellbeing. The evidence indicates that widely disseminating effective and efficient family- and school-based prevention programs can help to address both poverty itself and the effects of adverse social environments, making future poverty less likely. We conclude with specific recommendations for federal and state policymakers, researchers, and practitioners.

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.

Prospective, longitudinal study to isolate the impacts of marijuana use on neurocognitive functioning in adolescents.

Introduction: Policies to legalize possession and use of marijuana have been increasingly supported across the United States. Although there are restrictions on use in minors, many substance abuse scientists anticipate that these policy changes may alter use patterns among adolescents due to its wider availability and a softening of beliefs about its potentially harmful consequences. Despite the possibility that these policies may increase the prevalence of use among adolescents, the effects of marijuana on neurodevelopment remain unclear, clouding arguments in favor of or opposition to these policies. Methods: The present prospective, longitudinal study was designed to isolate the neurodevelopmental consequences of marijuana use from its precursors during adolescence-a period of heightened vulnerability for both substance use and disrupted development due to environmental insults. Early adolescents who were substance-naïve at baseline (N = 529, aged 10-12) were recruited and tracked into adolescence when a subgroup initiated marijuana use during one of three subsequent waves of data collection, approximately 18 months apart. Results: Results suggest that marijuana use may be specifically related to a decline in verbal learning ability in the short term and in emotion recognition, attention, and inhibition in the longer-term. Discussion: These preliminary findings suggest that marijuana use has potential to adversely impact vulnerable neurodevelopmental processes during adolescence. Intensive additional investigation is recommended given that state-level policies regulating marijuana use and possession are rapidly shifting in the absence of good scientific information.

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.

The mediating role of self-regulation on the link between child maltreatment and later substance use among Latinx youth.

BACKGROUND: Children who experience maltreatment are at heightened risk for substance use initiation and mental health disorders later in life. Few studies have assessed the relationship between child maltreatment and substance use among Latinx youth. OBJECTIVE: The current study assessed the potential mediating effect of three aspects of self-regulation (emotional, behavioral, and cognitive) on the association between child maltreatment and substance use and examined whether effects varied depending on maltreatment type and severity. PARTICIPANTS AND SETTING: This study involved a random sample of 504 Latinx youth (52 % girls, 48 % boys) between the ages of 10-12 at the start of the study. METHODS: Study hypotheses were tested through structural equation modeling and bootstrapped random errors using the R programming language. RESULTS: Our results indicated that higher levels of child maltreatment predicted higher levels of later substance use, as mediated by emotional and behavioral dysregulation (ß = 0.09, p < 0.01), but not cognitive regulation. When separating maltreatment by subtype, we found the mediating effect was present for abuse (ß = 0.09, p < 0.01), but not neglect. CONCLUSIONS: Findings contribute to our understanding of potential causal mechanisms for the association between child maltreatment and substance use for Latinx youth.

Capitalizing on Neuroplasticity Across Development to Redirect Pathways from Juvenile Justice Involvement.

Adolescence is an exquisitely sensitive period of development during which pathways branch toward success in school and prosocial pursuits or, conversely, toward behavior problems and involvement in high-risk activities and systems, such as juvenile justice (JJ). Adverse childhood experiences (ACEs) such as poverty, family dysfunction, and child maltreatment, have been strongly and repeatedly associated with JJ involvement. A significant body of research from neuroscience has established that ACEs can alter facets of neurodevelopment that undergird self-regulation throughout childhood and adolescence, thereby increasing susceptibility to behaviors that attract attention of the JJ system. Because the ability to intervene prior to system-entrenchment is crucial to disrupting an adverse developmental pathway, we look toward neuroscience to offer insights into how to do so more effectively. In this chapter, evidence is summarized that informs an understanding of how neurodevelopmental pathways may lead to JJ involvement. Because neurodevelopment is malleable in response to both detrimental and positive experiences, there is potential for well-targeted interventions to normalize brain and cognitive development, especially during sensitive periods of maturation. This discussion is followed by a proposed research agenda to determine how to exploit these critical windows of opportunity to divert youth from persistent antisocial behavior and JJ involvement. Lastly, a review of neuroscience findings regarding the ability of intervention to strengthen brain systems that modulate self-regulation is presented. This research has direct practical significance with potential to be translated into meaningful policy change.