Faculty Bibliography

Ethanol exposure in neonatal mice induces acute neurodegeneration followed by long-lasting glial activation and GABAergic cell deficits along with behavioral abnormalities, providing a third trimester model of fetal alcohol spectrum disorders (FASD). Retinoic acid (RA), the active form of vitamin A, regulates transcription of RA-responsive genes and plays essential roles in the development of embryos and their CNS. Ethanol has been shown to disturb RA metabolism and signaling in the developing brain, which may be a cause of ethanol toxicity leading to FASD. Using an agonist and an antagonist specific to RA receptor α (RARα), we studied how RA/RARα signaling affects acute and long-lasting neurodegeneration and activation of phagocytic cells and astrocytes caused by ethanol administered to neonatal mice. We found that an RARα antagonist (BT382) administered 30 min before ethanol injection into postnatal day 7 (P7) mice partially blocked acute neurodegeneration as well as elevation of CD68-positive phagocytic cells in the same brain area. While an RARα agonist (BT75) did not affect acute neurodegeneration, BT75 given either before or after ethanol administration ameliorated long-lasting astrocyte activation and GABAergic cell deficits in certain brain regions. Our studies using Nkx2.1-Cre;Ai9 mice, in which major GABAergic neurons and their progenitors in the cortex and the hippocampus are labeled with constitutively expressed tdTomato fluorescent protein, indicate that the long-lasting GABAergic cell deficits are mainly caused by P7 ethanol-induced initial neurodegeneration. However, the partial reduction of prolonged GABAergic cell deficits and glial activation by post-ethanol BT75 treatment suggests that, in addition to the initial cell death, there may be delayed cell death or disturbed development of GABAergic cells, which is partially rescued by BT75. Since RARα agonists including BT75 have been shown to exert anti-inflammatory effects, BT75 may rescue GABAergic cell deficits by reducing glial activation/neuroinflammation.

Reaching population-level impact for families in poverty requires moving beyond a sole focus on individuals, to a wider focus on interactions between individuals and their broader environmental contexts. Place-based initiatives have emerged as a policy response to promote community-level change around these broader interactions between individuals and their local communities through addressing long-standing disparities in housing, employment, education, and health. Together Growing Strong (TGS) is one such place-based initiative focused on transforming the health, wellbeing, and development of young children and their families in Sunset Park, Brooklyn. The Children, Caregivers, and Community (C3) Study is an outcomes-based study designed to assess the trajectories of children and families in Sunset Park along indicators such as family health and wellbeing and child development in relation to TGS program participation. The aims, scope, and protocol of the C3 Study are the subjects of this paper.

BACKGROUND:Peripartum adolescents experience significant interpersonal transitions in their lives. Depression and emotional distress are often exacerbated by adolescents' responses to these interpersonal changes. Improved understanding of pregnancy-related social changes and maladaptive responses to these shifts may inform novel approaches to addressing the mental health needs of adolescents during the perinatal period. The paper aims to understand the sources of psychological distress in peripartum adolescents and map these to Interpersonal Psychotherapy's (IPT) problem areas as a framework to understand depression. METHOD/METHODS:We conducted interviews in two Nairobi primary care clinics with peripartum adolescents ages 16-18 years (n = 23) with experiences of depression, keeping interpersonal psychotherapy framework of problem areas in mind. We explored the nature of their distress, triggers, antecedents of distress associated with an unplanned pregnancy, quality of their relationships with their partner, parents, and other family members, perceived needs, and sources of support. RESULTS:We found that the interpersonal psychotherapy (IPT) framework of interpersonal problems covering grief and loss, role transitions, interpersonal disputes, and social isolation was instrumental in conceptualizing adolescent depression, anxiety, and stress in the perinatal period. CONCLUSION/CONCLUSIONS:Our interviews deepened understanding of peripartum adolescent mental health focusing on four IPT problem areas. The interpersonal framework yields meaningful information about adolescent depression and could help in identifying strategies for addressing their distress.

OBJECTIVES:To summarise evidence on intrawork breaks and their associated effect on doctors' well-being and/or performance at work. DESIGN:Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement guidelines DATA SOURCES: Embase, PubMed, Web of Science (Core Collection) and PsychINFO were systematically searched on 6 June 2021. ELIGIBILITY CRITERIA:No restrictions were placed on language, study design or date of publication. DATA EXTRACTION AND ANALYSIS:Methodological quality was appraised using Cochrane's Risk of Bias (ROB-2), Cochrane's Risk of Bias in Non-randomised Studies (ROBINS-I), and the Johanna Briggs Institute (JBI) checklists for cross-sectional, cohort and qualitative studies. Quantitative synthesis was not undertaken due to substantial heterogeneity of design and outcomes. Results are presented narratively. RESULTS:Database searches returned 10 557 results and searches of other sources returned two additional records. Thirty-two papers were included in the systematic review, comprised of 29 unique studies, participants and topics and 3 follow-up studies. A variety of well-being and performance outcome measures were used. Overall, findings indicate that intrawork breaks improved some measures of well-being and/or work performance. However, methodological quality was judged to be low with a high risk of bias in most included studies. DISCUSSION:Using existing evidence, it is not possible to conclude with confidence whether intrawork breaks improve well-being and/or work performance in doctors. There is much inconsistency regarding how breaks are defined, measured and the outcomes used to assess effectiveness. Future research should seek to: (a) define and standardise the measurement of breaks, (b) use valid, reliable outcome measures to evaluate their impact on well-being and performance and (c) minimise the risk of bias in studies where possible. PROSPERO REGISTRATION NUMBER:CRD42020156924; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=156924.

BACKGROUND:Children referred for attention-deficit/hyperactivity disorder (ADHD) often present with a broader pattern of conduct problems including oppositionality and defiance. This combination can be extremely stressful to parents, lower parents' self-esteem and negatively impact family life. The National Institute for Health and Care Excellence (NICE) recommends that families receive support as soon as possible after their referral. However, as clinical services are overstretched, and traditional in-person parenting intervention programmes are expensive, families often must wait times a long time prior to receiving this vital input. To address this, we have created a digital parenting programme called STEPS. It is delivered as a mobile phone app providing a set of tools and resources that can be easily accessed at parents' convenience. This study aims to evaluate the clinical and cost-effectiveness of STEPS in supporting parents of children with high levels of hyperactivity/impulsivity, inattention and conduct problems, who are waiting to be assessed by specialist children's clinical services. METHODS:Online Parent Training for The Initial Management of ADHD referrals (OPTIMA) is a two-arm superiority parallel randomised controlled trial with an internal pilot study. We aim to recruit 352 parents and their children, who have been accepted onto a waitlist in Child and Adolescent Mental Health Services or similar child health services. Parents who consent will be randomised 1:1 to either the STEPS or wait-as-usual (WAU) group. The trial will be conducted remotely (online and telephone) with measures taken at baseline and 3, 6, 9 and 12 months post-randomisation. The primary objective is to evaluate whether STEPS reduces the severity of children's oppositional and defiant behaviour, as rated by parents, measured at 3 months post-randomisation compared to WAU. DISCUSSION/CONCLUSIONS:Digital solutions, such as mobile phone apps, have potential for delivering psychological support for parents of children with clinical-level needs in a timely and inexpensive manner. This trial will provide data on the clinical and cost-effectiveness of the STEPS app, which could support the implementation of this scalable parenting intervention programme into standard clinical care and, ultimately, improve the outcomes for families of children referred to specialist child and adolescent health services. TRIAL REGISTRATION/BACKGROUND:ISRCTN 16523503. Prospectively registered on 18 November 2021. https://www.isrctn.com/ISRCTN16523503.