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The relationship between developmental exposure to adversity and affective disorders is reviewed. Adversity discussed herein includes physical and sexual abuse, neglect, or loss of a caregiver in humans. While these stressors can occur at any point during development, the unique temporal relationship to specific depressive symptoms was the focus of discussion. Further influences of stress exposure during sensitive periods can vary by gender and duration of abuse as well. Data from animal studies are presented to provide greater translational and causal understanding of how sensitive periods, different types of psychosocial stressors, and sex interact to produce depressive-like behaviors. Findings from maternal separation, isolation rearing, chronic variable stress, and peer–peer rearing paradigms clarify interpretation about how various depressive behaviors are influenced by age of exposure. Depressive behaviors are broken down into the following categories: mood and affect, anhedonia, energy, working memory, sleep–wake, appetite changes, suicide, and general malaise. Cross-species evidence from humans, nonhuman primates, rats, and mice within each of these categories is discussed. In conclusion, sensitive periods for affective-related behaviors (anxiety, mood, and controllability) occur earlier in life, while other aspects of depression are associated with adversity later during adolescence.

Background Sleep is essential for child and adolescent health and well-being. There is an increasing interest in whether electronic media use affects children and young adolescents’ sleep. Prior reviews have focused on a school-aged population. Moreover, it is crucial that research continuously addresses the processes of technology and media use and the implication on sleep. This systematic review examines the evidence of electronic media use related to sleep among 0–15-year-olds. Methods Searches were carried out in four databases (CINAHL, Web of Science, EMBASE, and Medline). Inclusion criteria included age ≤ 15 years, and intervention, cohort, or cross-sectional studies from western countries. Methodological quality was rated using the Quality Assessment Tool for Quantitative Studies by two independent reviewers. Data was extracted using a standardized data extraction form. Synthesis was done by summarizing results across studies by age groups of 0–5, 6–12, and 13–15 years within four sleep domains: Bedtime and sleep onset; Sleep quality; Sleep duration; Daytime tiredness. Results The search identified 10,719 unique studies, of which 109 fulfilled inclusion and exclusion criteria and were assessed for methodological quality. In total, 49 studies were included in the review. The study designs were randomized controlled trials ( n  = 3), quasi-experimental studies ( n  = 2), prospective cohort studies ( n  = 15), and cross-sectional studies ( n  = 29). Evidence for an association between electronic media use and sleep duration was identified, with stronger evidence for 6–15-years-olds than 0–5-year-olds. The evidence for a relationship between electronic media use and other sleep outcomes was more inconclusive. However, for 6–12-year-old children, there was evidence for associations of electronic media use with delayed bedtime and poor sleep quality. For 13–15-year-olds, there was evidence for associations between screen time and problems falling asleep, and between social media use and poor sleep quality. Conclusions Overall, electronic media use was generally associated with shorter sleep duration in children and adolescents. Studies with stronger research design and of higher quality are needed to draw solid conclusions about electronic media’s impact on other sleep outcomes. Public awareness and interventions could be promoted about the potential negative impact on children’s sleep of electronic media devices that are used excessively and close to bedtime.

Early adversity, the loss of the inhibitory GABAergic interneuron parvalbumin, and elevated neuroinflammation are associated with depression. Individuals with a maltreatment history initiate medicinal cannabis use earlier in life than non-maltreated individuals, suggesting self-medication. Female rats underwent maternal separation (MS) between 2 and 20 days of age to model early adversity or served as colony controls. The prelimbic cortex and behavior were examined to determine whether MS alters the cannabinoid receptor 2 (CB2), which has anti-inflammatory properties. A reduction in the CB2-associated regulatory enzyme MARCH7 leading to increased NLRP3 was observed with Western immunoblots in MS females. Immunohistochemistry with stereology quantified numbers of parvalbumin-immunoreactive cells and CB2 at 25, 40, and 100 days of age, revealing that the CB2 receptor associated with PV neurons initially increases at P25 and subsequently decreases by P40 in MS animals, with no change in controls. Confocal and triple-label microscopy suggest colocalization of these CB2 receptors to microglia wrapped around the parvalbumin neuron. Depressive-like behavior in MS animals was elevated at P40 and reduced with the CB2 agonist HU-308 or a CB2-overexpressing lentivirus microinjected into the prelimbic cortex. These results suggest that increasing CB2 expression by P40 in the prelimbic cortex prevents depressive behavior in MS female rats.

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.

Rationale Most substance use is initiated during adolescence when substantial development of relevant brain circuitry is still rapidly maturing. Developmental differences in reward processing, behavioral flexibility, and self-regulation lead to changes in resilience or vulnerability to drugs of abuse depending on exposure to risk factors. Intervention and prevention approaches to reducing addiction in teens may be able to capitalize on malleable brain systems in a predictable manner. Objective This review will highlight what is known about how factors that increase vulnerability to addiction, including developmental stage, exposure to early life adversity (ranging from abuse, neglect, and bullying), drug exposure, and genetic predisposition, impact the development of relevant systems. Results and conclusions Appropriate, early intervention may restore the normal course of an abnormal trajectory and reduce the likelihood of developing a substance use disorder (SUD) later in life. A considerable amount is known about the functional neuroanatomy and/or pharmacology of risky behaviors based on clinical and preclinical studies, but relatively little has been directly translated to reduce their impact on addiction in high-risk children or teenagers. An opportunity exists to effectively intervene before adolescence when substance use is likely to emerge.

Early maternal separation has been shown in animal models to produce enduring morphological changes in the hippocampus and other brain structures, which may not become evident until adulthood. Postnatally, the trajectory of overproduction and pruning of axons, dendrites, synapses and receptors shapes the brain between puberty and adulthood. The objective of the study was to ascertain whether this normal trajectory was affected by repeated maternal separation. Rat pups were separated from their mother for 4 h a day between postnatal days 2 and 20 (ISO group), and compared to rat pups that remained with their mother in the animal facilities (AFR group) and were exposed to minimal handling. Immunoreactivity to synaptophysin was quantified in the hippocampus CA1 and CA3, amygdala, and prefrontal cortex using optical densitometry (OD) at 25, 40, 60, 80, and 100 days in male and female rats. Synaptophysin OD increased dramatically in CA1 and CA3 between 25 and 60 days in the AFR group and fell by the same degree between 60 and 100 days, showing the expected sequence of overproduction and pruning. No difference between groups in synaptophysin OD was observed at 25 and 40 days. However, at day 60 synaptophysin was 34-36% lower in CA1 and CA3 of the ISO group, and remained 24-26% lower at 100 days. Early isolation produced no enduring reduction in synaptophysin OD in the amygdala or prefrontal cortex. Overall, these results suggest that early maternal separation produced a regionally specific delayed effect on the structure of the hippocampus by attenuating rates of synaptic development.

Background Most adult smokers started smoking in their teenage years, which increases the risk of nicotine dependence. In Denmark, there is a high prevalence of youth smoking among students in Vocational Education and Training (VET). However, reducing and preventing smoking in this group is a major challenge. This article presents a needs assessment aimed to explore factors sustaining legitimacy of smoking in VET schools and consider the measures needed to prepare VET schools’ implementation of smoking reduction and prevention interventions. Methods Participant observations were conducted in four VET classes representing three VET schools in Denmark with a duration of four days each. Individual, semi-structured interviews were conducted with teachers, managers, and a student advisor, as well as four focus groups with a total of 20 students. Interviews were audio-taped, transcribed, and the data material was analyzed following Malterud’s systematic text condensation. Findings Factors that helped sustain legitimacy of smoking in VET schools included a positive and normalized attitude towards smoking at home and among friends, an understanding of smoking as an integral and expected practice in VET professions and schools, a perceived reliance on smoking as an icebreaker in new social relations and as a pedagogical tool, and smoking as a habit and a means to deal with boredom and stress relief. Conclusions The factors sustaining legitimacy of smoking in VET schools are reciprocal and call for smoking reduction and prevention intervention efforts which consider and address social influence, habitual behavior, and psychological needs, as well as changes at the policy level.

Rationale Adolescents are often described as “lacking brakes” resulting in an increase in several behaviors associated with risk for addiction. Prefrontal cortex dopamine and cortico-limbic interaction play an important role in addiction, and we have previously shown that the dopamine D1 receptor is elevated on prelimbic prefrontal output neurons in adolescent rats. We hypothesized that a constellation of risk-related behaviors is mediated by prefrontal output neuron expression of D1. Objectives We aimed to determine the role of the dopamine D1 receptor in behavioral and neural correlates of risk for addiction that are often observed in adolescents. Therefore, high-risk behaviors as well as subcortical D2 receptor expression were investigated in adult animals with experimentally elevated D1 on prefrontal glutamatergic neurons. Methods A lentiviral vector that selectively expressed the D1 receptor within glutamate neurons was injected in the prelimbic prefrontal cortex of adult male rats. Place conditioning to cocaine, alcohol, and nicotine, as well as delay discounting, novelty preferences, anxiety, cocaine self-administration, and sucrose preferences were assessed. Results Virally mediated D1 over-expression in adults leads to stronger drug-cue associations and greater consumption of sweet solutions, elevates bias towards immediate satisfaction rather than delaying gratification, decreases anxiety, and causes rats to work harder for and take more cocaine. Furthermore, elevated cortical D1 reduces D2 receptors in the accumbens (a putative risk marker). Conclusions Together, these data suggest a common mechanism for increased motivational drive to seek and consume substances with hedonic value, consistent with adolescent addictive processes.

Background Social inequality in smoking remains an important public health issue. Upper secondary schools offering vocational education and training (VET) comprise more students from lower socioeconomic backgrounds and have higher smoking prevalence than general high schools. This study examined the effects of a school-based multi-component intervention on students’ smoking. Methods A cluster randomized controlled trial. Eligible participants were schools offering VET basic courses or preparatory basic education in Denmark, and their students. Schools were stratified by subject area and eight schools were randomly allocated to intervention (1,160 invited students; 844 analyzed) and six schools to control (1,093 invited students; 815 analyzed). The intervention program comprised smoke-free school hours, class-based activities, and access to smoking cessation support. The control group was encouraged to continue with normal practice. Primary outcomes were daily cigarette consumption and daily smoking status at student level. Secondary outcomes were determinants expected to impact smoking behavior. Outcomes were assessed in students at five-month follow-up. Analyses were by intention-to-treat and per protocol (i.e., whether the intervention was delivered as intended), adjusted for covariates measured at baseline. Moreover, subgroup analyses defined by school type, gender, age, and smoking status at baseline were performed. Multilevel regression models were used to account for the cluster design. Missing data were imputed using multiple imputations. Participants and the research team were not blinded to allocation. Results Intention-to-treat analyses showed no intervention effect on daily cigarette consumption and daily smoking. Pre-planned subgroup analyses showed statistically significant reduction in daily smoking among girls compared with their counterparts in the control group (OR = 0.39, 95% CI: 0.16, 0.98). Per-protocol analysis suggested that schools with full intervention had higher benefits compared with the control group (daily smoking: OR = 0.44, 95% CI: 0.19, 1.02), while no marked differences were seen among schools with partial intervention. Conclusion This study was among the first to test whether a complex, multicomponent intervention could reduce smoking in schools with high smoking risk. Results showed no overall effects. There is a great need to develop programs for this target group and it is important that they are fully implemented if an effect is to be achieved. Trial registration https://www.isrctn.com/ISRCTN16455577 , date of registration 14/06/2018.