Faculty Bibliography

Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they should be used in this population. This meta-review aimed to assess the effects of antidepressants for the acute treatment of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ADs), autistic spectrum disorder (ASD), enuresis, major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) in children and adolescents. Efficacy was measured as response to treatment (either as mean overall change in symptoms or as a dichotomous outcome) and tolerability was measured as the proportion of patients discontinuing treatment due to adverse events. Suicidality was measured as suicidal ideation, behavior (including suicide attempts) and completed suicide. PubMed, EMBASE, and Web of Science were systematically searched (until 31 October 2019) for existing systematic reviews and/or meta-analyses of double-blind randomized controlled trials. The quality of the included reviews was appraised using AMSTAR-2. Our meta-review included nine systematic reviews/meta-analyses (2 on ADHD; 1 on AD; 2 on ASD; 1 on enuresis; 1 on MDD, 1 on OCD and 1 on PTSD). In terms of efficacy this review found that, compared to placebo: fluoxetine was more efficacious in the treatment of MDD, fluvoxamine and paroxetine were better in the treatment of AD; fluoxetine and sertraline were more efficacious in the treatment of OCD; bupropion and desipramine improved clinician and teacher-rated ADHD symptoms; clomipramine and tianeptine were superior on some of the core symptoms of ASD; and no antidepressant was more efficacious for PTSD and enuresis. With regard to tolerability: imipramine, venlafaxine, and duloxetine were less well tolerated in MDD; no differences were found for any of the antidepressants in the treatment of anxiety disorders (ADs), ADHD, and PTSD; tianeptine and citalopram, but not clomipramine, were less well tolerated in children and adolescents with ASD. For suicidal behavior/ideation, venlafaxine (in MDD) and paroxetine (in AD) were associated with a significantly increased risk; by contrast, sertraline (in AD) was associated with a reduced risk. The majority of included systematic reviews/meta-analyses were rated as being of high or moderate in quality by the AMSTAR-2 critical appraisal tool (one and five, respectively). One included study was of low quality and two were of critically low quality. Compared to placebo, selected antidepressants can be efficacious in the acute treatment of some common psychiatric disorders, although statistically significant differences do not always translate into clinically significant results. Little information was available about tolerability of antidepressants in RCTs of OCD and in the treatment of ADHD, ASD, MDD, and PTSD. There is a paucity of data on suicidal ideation/behavior, but paroxetine may increase the risk of suicidality in the treatment of AD and venlafaxine for MDD. Findings from this review must be considered in light of potential limitations, such as the lack of comparative information about many antidepressants, the short-term outcomes and the quality of the available evidence.

Sustaining evidence-based practices after initial training and support has ended is necessary to ensure lasting improvements in youth mental health services. This study examined factors impacting community clinicians' decisions to sustain a transdiagnostic youth intervention following participation in a study. The aim of the study was to identify potentially mutable factors impacting sustainability to inform future implementation efforts. Thirteen clinicians (85% women, 92% Caucasian, M age = 35.6) completed interviews after participating in an open trial of an evidence-based intervention for depression, anxiety, and conduct disorders. Interviews were analyzed using thematic analysis methods. All (100%) clinicians reported current use of the intervention. Four themes emerged related to sustainability. Clinicians (100%) reported that making modifications, alignment with prior training, and relative advantage influenced their current intervention use. Clinicians (100%) reported that knowledge transfer from treatment developers was vital to sustainability. They (92%) noted a number of logistical, inner-organizational, and client-level barriers to sustainability. Lastly, clinicians (92%) identified factors related to scaling up the intervention. A variety of personal, organizational, logistical, and client variables influence the sustainment of new interventions, and could be leveraged in future implementation efforts.

Ethnic South Asian Americans (SAAs) have the highest relative risk of type 2 diabetes mellitus (T2DM) in the United States (US). Culturally tailored lifestyle interventions have the potential to promote South Asian diabetes prevention; however, the extent of their use and evaluation in US settings remains limited. This systematic review characterizes and evaluates outcomes of community-based lifestyle interventions targeted towards T2DM indicators among South Asians living in the US. A PRISMA-informed search of Pubmed, Embase, Cochrane, Web of Science, and clinical trial registry databases using key words pertaining to South Asians migrants and diabetes indicators (glucose and insulin outcomes) was conducted of community-based lifestyle interventions published up until October, 31 2019. Of the eight studies included in the final synthesis, four interventions focused on cultural and linguistic adaptations of past chronic disease prevention curricula using group-based modalities to deliver the intervention. Hemoglobin A1c (A1c) was the most common outcome indicator measured across the interventions. Three of the five studies observed improvements in indicators post-intervention. Based on these findings, this review recommends 1) greater exploration of community-based lifestyle interventions with high quality diabetes indicators (such as fasting blood glucose) in ethnic SAA communities, 2) expanding beyond traditional modalities of group-based lifestyle interventions and exploring the use of technology and interventions integrated with passive, active, and individualized components, and 3) development of research on diabetes prevention among second generation SAAs.

Allocating access to unapproved COVID-19 drugs available via Pre-Approval Access pathways or Emergency Use Authorization raises unique challenges at the intersection of clinical care and research. In conditions of scarcity, prioritization approaches should minimize harm, maximize benefit, and promote fairness. To promote continued data collection, patients seeking access to unproven COVID-19 drugs should receive lower priority for allocation when they decline to participate in clinical trials, either of the requested drug or other investigational products, offering a comparable balance of risks and benefits; special attention should be paid to concerns of voluntariness and distrust. In addition, institutional treatment protocols that can contribute more robust real world data should be preferred to single patient requests for access, with priority for inclusion based on traditional clinical allocation criteria relying on available evidence. Fairness demands distribution of these protocols across a diverse range of sites, particularly those serving marginalized populations, among other protections.

In this My Word, Joseph LeDoux and Hakwan Lau argue that everyday human conscious experiences cannot be understood separately from memory. The authors build on a tripartite model of memory as a way of fractionating consciousness into components that account for wide ranging experiences, from the simplest sensory experience of the color of an apple to a full-blown feeling of fear or other emotions.

Developmental exposure to ethanol has a wide range of anatomical, cellular, physiological and behavioral impacts that can last throughout life. In humans, this cluster of effects is termed fetal alcohol spectrum disorder and is highly prevalent in western cultures. The ultimate expression of the effects of developmental ethanol exposure however can be influenced by post-exposure experience. Here we examined the effects of developmental binge exposure to ethanol (postnatal day 7) in C57BL/6By mice on a specific cohort of inter-related long-term outcomes including contextual memory, hippocampal parvalbumin-expressing neuron density, frontal cortex oscillations related to sleep-wake cycling including delta oscillation amplitude and sleep spindle density, and home-cage behavioral activity. When assessed in adults that were raised in standard housing, all of these factors were altered by early ethanol exposure compared to saline controls except home-cage activity. However, exposure to an enriched environment and exercise from weaning to postnatal day 90 reversed most of these ethanol-induced impairments including memory, CA1 but not dentate gyrus PV+ cell density, delta oscillations and sleep spindles, and enhanced home-cage behavioral activity in Saline- but not EtOH-treated mice. The results are discussed in terms of the inter-dependence of diverse developmental ethanol outcomes and potential mechanisms of post-exposure experiences to regulate those outcomes.

Delineating common and separable neural alterations in substance use disorders (SUD) is imperative to understand the neurobiological basis of the addictive process and to inform substance-specific treatment strategies. Given numerous functional MRI (fMRI) studies in different SUDs, a meta-analysis could provide an opportunity to determine robust shared and substance-specific alterations. The present study employed a coordinate-based meta-analysis covering fMRI studies in individuals with addictive cocaine, cannabis, alcohol, and nicotine use. The primary meta-analysis demonstrated common alterations in primary dorsal striatal, and frontal circuits engaged in reward/salience processing, habit formation, and executive control across different substances and task-paradigms. Subsequent sub-analyses revealed substance-specific alterations in frontal and limbic regions, with marked frontal and insula-thalamic alterations in alcohol and nicotine use disorders respectively. Examining task-specific alterations across substances revealed pronounced frontal alterations during cognitive processes yet stronger striatal alterations during reward-related processes. Finally, an exploratory meta-analysis revealed that neurofunctional alterations in striatal and frontal reward processing regions can already be determined with a high probability in studies with subjects with comparably short durations of use. Together the findings emphasize the role of dysregulations in frontostriatal circuits and dissociable contributions of these systems in the domains of reward-related and cognitive processes which may contribute to substance-specific behavioral alterations.

BACKGROUND:The C8 Science Panel was composed of three epidemiologists charged with studying the possible health effects of PFOA in a highly exposed population in the mid-Ohio Valley. The Panel determined in 2012 there was a 'probable link' (i.e., more probable than not based on the weight of the available scientific evidence) between PFOA and high cholesterol, thyroid disease, kidney and testicular cancer, pregnancy-induced hypertension, and ulcerative colitis. OBJECTIVE:Here, former C8 Science Panel members and collaborators comment on the PFOA literature regarding thyroid disorders, cancer, immune and auto-immune disorders, liver disease, hypercholesterolemia, reproductive outcomes, neurotoxicity, and kidney disease. We also discuss developments regarding fate and transport, and pharmacokinetic models, and discuss causality assessment in cross-sectional associations among low-exposed populations. DISCUSSION/CONCLUSIONS:For cancer, the epidemiologic evidence remains supportive but not definitive for kidney and testicular cancers. There is consistent evidence of a positive association between PFOA and cholesterol, but no evidence of an association with heart disease. There is evidence for an association with ulcerative colitis, but not for other auto-immune diseases. There is good evidence that PFOA is associated with immune response, but uneven evidence for an association with infectious disease. The evidence for an association between PFOA and thyroid and kidney disease is suggestive but uneven. There is evidence of an association with liver enzymes, but not with liver disease. There is little evidence of an association with neurotoxicity. Suggested reductions in birthweight may be due to reverse causality and/or confounding. Fate and transport models and pharmacokinetic models remain central to estimating past exposure for new cohorts, but are difficult to develop without good historical data on emissions of PFOA into the environment. CONCLUSION/CONCLUSIONS:Overall, the epidemiologic evidence remains limited. For a few outcomes there has been some replication of our earlier findings. More longitudinal research is needed in large populations with large exposure contrasts. Additional cross-sectional studies of low exposed populations may be less informative.

Flexibility and generativity are fundamental aspects of functional behavior that begin in infancy and improve with experience. How do infants learn to tailor their real-time solutions to variations in local conditions? On a nativist view, the developmental process begins with innate prescribed solutions, and experience elaborates on those solutions to suit variations in the body and the environment. On an emergentist view, infants begin by generating a variety of strategies indiscriminately, and experience teaches them to select solutions tailored to the current relations between their body and the environment. To disentangle these accounts, we observed coordination patterns in 11-month-old pre-walking infants with a range of cruising (moving sideways in an upright posture while holding onto a support) and crawling experience as they cruised over variable distances between two handrails they held for support. We identified infants' coordination patterns using a novel combination of computer-vision, machine-learning, and time-series analyses. As predicted by the emergentist view, the least experienced infants generated multiple coordination patterns inconsistently regardless of body size and handrail distance, whereas the most experienced infants tailored their coordination patterns to body-environment relations and switched solutions only when necessary. Moreover, the beneficial effects of experience were specific to cruising and not crawling, although both skills involve anti-phase coordination among the four limbs. Thus, findings support an emergentist view and suggest that everyday experience with the target skill may promote "learning to learn," where infants learn to assemble the appropriate solution for new problems on the fly.