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Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

AbstractChronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

This study assessed the effectiveness of employment programs components, which resulted in the identification of content and process components that increase employability. Employment program use was studied among 1172 United States of America military veterans to determine which content (i.e., interviewing skills) and process (i.e., working with a mentor/coach) components influence job attainment during a time of career and identity transition. Components were distilled utilizing a common components analysis approach (Morgan et al., 2018). Associations with finding employment up to 15 months after the military-to-civilian transition were explored. Veterans who engaged with employment programs were primarily accessing the following components: career planning, resume writing, and interviewing skills. However, only a few content components were significantly related to obtaining employment: interviewing (with mentor/coach), resume writing (online tools), translating military to civilian work (with mentor/coach), entrepreneurship (with mentor/coach), and virtual career fairs. Furthermore, not all processes or modes of instruction for content components were associated with success in the job market. Having a mentor/coach was one of the most effective delivery strategies. For example, veterans using programs delivered by a mentor/coach that translated military skills to civilian work were more likely to find a job at 6-9-months (84%) and 12-15-months (91%) post military separation. In addition, risks that predicted lower use of employment program components by veterans were identified such as junior enlisted rank, combat exposure, combat arms occupation, and physical health problems. With these findings, program developers, implementers, and funders can channel efforts towards the utilization of employment programs with effective components.

PurposeSince 2011, US authorities have supported the following 2 approaches to healthier body fat composition: the Centers for Disease Control and Prevention National Diabetes Prevention Program's calorie counting (CC) approach and the US Department of Agriculture's MyPlate (adherence to federal nutrition guidelines). The purpose of this study was to compare the effect of CC vs MyPlate approaches on satiety/satiation and on achieving healthier body fat composition among primary care patients.MethodsWe conducted a randomized controlled trial comparing the CC and MyPlate approaches from 2015 to 2017. The adult participants were overweight, of low income, and were mostly Latine (n = 261). For both approaches, community health workers conducted 2 home education visits, 2 group education sessions, and 7 telephone coaching calls over a period of 6 months. Satiation and satiety were the primary patient-centered outcome measures. Waist circumference and body weight were the primary anthropometric measures. Measures were assessed at baseline, 6 months, and 12 months.ResultsSatiation and satiety scores increased for both groups. Waist circumference was significantly decreased in both groups. MyPlate, but not CC, resulted in lower systolic blood pressure at 6 months but not at 12 months. Participants for both MyPlate and CC reported greater quality of life and emotional well-being and high satisfaction with their assigned weight-loss program. The most acculturated participants showed the greatest decreases in waist circumference.ConclusionsA MyPlate-based intervention might be a practical alternative to the more traditional CC approach to promoting satiety and facilitating decreases in central adiposity among low-income, mostly Latine primary care patients.

Using national data from the National Center for Education Statistics 2011-2012 Schools and Staffing Survey and Common Core of Data, we examined the relationship between K-12 practitioners' risk for stress and the teacher-to-student racial/ethnic congruence. Analyses indicated significant variation in risk for stress by school racial composition and suggested that the likelihood of being categorized as most at-risk for stress is associated with the teacher-to-student racial/ethnic congruence. Findings point to substantial differences in how teachers appraise their environments depending on school context, which has implications for how education stakeholders recruit and prepare classroom practitioners.

Equity for students includes access to a healthy teacher workforce across all school settings. This study sought to disentangle the role of racial/ethnic (in)congruence in teacher stress from school resources by using propensity score analysis to match Black, Hispanic, and White elementary teachers on individual, classroom, and school characteristics, and examining whether these matched teachers reported differences in stress outcomes when working in schools where the predominant student demography was either congruent or incongruent with their own. Data from the 2015-2016 National Teacher and Principal Survey was used to find propensity score matches among 7540 Black, Hispanic, and White elementary teachers. Black, Hispanic, and White teachers all reported stronger occupational health outcomes in higher-resourced, majority-White schools. Black and Hispanic teachers reported higher levels of occupational health outcomes than White teachers when teaching in under-resourced, majority-minority schools. These findings suggest important implications for teacher training and support, such as considering increased training and reflection opportunities on culturally responsive teaching, broadening policies that homogeneously categorize and aim to uniformly support "teachers of color," and examining the ways in which teacher identity uniquely informs their workplace experiences and may necessitate differentiated resources.

Teacher stress continues to threaten the stability of the U.S. teaching workforce, but teacher mentoring, an increasingly prevalent type of teacher support, may uniquely support teachers with their risk-for-stress. The current study investigated how teacher mentoring experiences differ based on vulnerability to stress and teacher experience level. Semi-structured focus groups were conducted and analysed using the Consensual Qualitative Research (CQR) method. Results include five emergent domains indicating that teachers viewed mentoring as overwhelmingly supportive of their instructional needs, regardless of their stress risk or experience level. New and experienced teachers also shared similar experiences regarding the social emotional support that mentoring can provide. However, differing trends emerged between risk-for-stress groups in their reports of mentoring qualities and challenges, which may signal the need for differentiating mentoring supports based on teacher stress levels.

Supporting and retaining U.S. K-12 beginning teachers remains a problem and has been linked to early career stress. Although teacher induction programs for beginning teachers have flourished in recent decades, beginning teacher stress persists and can undermine their occupational health. Teacher mentoring has been identified as an important way to support beginning teachers. To add to the literature in this area, the present study examines associations between mentoring experiences and first-year teacher stress. Using 1,980 responses to the 2007-08 Beginning Teacher Longitudinal Survey, scale scores were created for teacher appraisals of demands and resources and mentoring frequency and helpfulness. Teachers who identified classroom demands as exceeding resources (32.8%) reported significantly fewer (d = 0.20) and less helpful mentoring experiences (d = 0.19) than teachers rating demands and resources as equal. Teachers with higher resources than demands (21.9%) reported significantly greater (d = 0.20) and more helpful mentoring experiences (d = 0.32).

Combining secondary data from the National Center for Education Statistics National Teacher Principal Survey (NTPS) and Common Core of Data (CCD), this exploratory study examined the distribution of teacher race/ethnicity across the race/ethnicity of the schools in which they work and the extent that teacher and school race/ethnicity was associated with occupational stress. Findings indicate that teachers are more likely to work in schools with higher concentrations of students who match their own race/ethnicity. Both teacher and school race/ethnicity were unique predictors of a teacher being classified as at-risk for stress. Additional analyses suggested that teachers' reported race/ethnicity significantly moderated the school effect association with stress risk. These findings have policy implications for how school workplace survey s are used as well as staffing and professional development considerations.

BackgroundCollege campuses have policies restricting smoking/vaping on campus. Previous studies involving mostly European-American students showed smoking prevalence declines following implementation of such policies.ObjectiveTo evaluate a social media campaign promotive of stronger campus support for an existing campus no-smoking/no-vaping policy where most (∼75%) of the undergraduates were non-European-American. A demographically comparable university served as a no-intervention control.ParticipantsTarget was 200 random intercept surveys at each university during fall 2016, spring 2017. Of 800 respondents, 681 were undergraduates.MethodsBaseline and post-intervention surveys assessed awareness of and support for campus-wide smoke-free/vape-free policies. Staged smoke-free/vape-free policy violations assessed students' propensity to intervene in support of the policy.ResultsRespondent support for the no-smoking/no-vaping policy did not change.ConclusionsThe social media campaign and Policy Ambassadors program did not increase support for the campus no-smoking/no-vaping policy. Most (∼90%) respondents agreed that the campus no-smoking/no-vaping policy was important for public health.

AimSymptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many of these processes are regulated by circadian function, circadian rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence for neurobiological and behavioral mechanisms pertinent to BD.MethodDrawing upon expertise in animal models, biomarkers, physiology, and behavior, CTF analyzed the relevant cross-disciplinary literature to precisely frame the discussion around circadian rhythm disruption in BD, highlight key findings, and for the first time integrate findings across levels of analysis to develop an internally consistent, coherent theoretical framework.ResultsEvidence from multiple sources implicates the circadian system in mood regulation, with corresponding associations with BD diagnoses and mood-related traits reported across genetic, cellular, physiological, and behavioral domains. However, circadian disruption does not appear to be specific to BD and is present across a variety of high-risk, prodromal, and syndromic psychiatric disorders. Substantial variability and ambiguity among the definitions, concepts and assumptions underlying the research have limited replication and the emergence of consensus findings.ConclusionsFuture research in circadian rhythms and its role in BD is warranted. Well-powered studies that carefully define associations between BD-related and chronobiologically-related constructs, and integrate across levels of analysis will be most illuminating.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a common and disabling disorder primarily characterized by persistent fatigue and exercise intolerance, with associated sleep disturbances, autonomic dysfunction, and cognitive problems. The causes of ME/CFS are not well understood but may coincide with immune and inflammatory responses following viral infections. During the current SARS-CoV2 coronavirus pandemic, ME/CFS has been increasingly reported to overlap with persistent "long COVID" symptoms, also called the post-acute sequelae of COVID-19 (PASC). Given the prominence of activity and sleep problems in ME/CFS, circadian rhythm disruption has been examined as a contributing factor in ME/CFS. While these studies of circadian rhythms have been pursued for decades, evidence linking circadian rhythms to ME/CFS remains inconclusive. A major limitation of older chronobiology studies of ME/CFS was the unavailability of modern molecular methods to study circadian rhythms and incomplete understanding of circadian rhythms outside the brain in peripheral organ systems. Major methodological and conceptual advancements in chronobiology have since been made. Over the same time, biomarker research in ME/CFS has progressed. Together, these new developments may justify renewed interest in circadian rhythm research in ME/CFS. Presently, we review ME/CFS from the perspective of circadian rhythms, covering both older and newer studies that make use of modern molecular methods. We focus on transforming growth factor beta (TGFB), a cytokine that has been previously associated with ME/CFS and has an important role in circadian rhythms, especially in peripheral cells. We propose that disrupted TGFB signaling in ME/CFS may play a role in disrupting physiological rhythms in sleep, activity, and cognition, leading to the insomnia, energy disturbances, cognition problems, depression, and autonomic dysfunction associated with ME/CFS. Since SARS-like coronavirus infections cause persistent changes in TGFB and previous coronavirus outbreaks have caused ME/CFS-like syndromes, chronobiological considerations may have immediate implications for understanding ME/CFS in the context of the COVID-19 pandemic and possibly suggest new avenues for therapeutic interventions.