Faculty Bibliography

OBJECTIVE:People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population. METHODS:Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age). RESULTS:Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES). CONCLUSIONS:Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.

Elevated exposure to multiple trace metals can be neurotoxic even at relatively low levels. These findings are primarily evident from adult occupational studies as well as in children exposed prenatally or in early childhood. Less research has focused on the neurodevelopmental impacts of exposure to metals among school-aged children. We examined associations between exposure to a mixture of four metals (arsenic, cadmium, manganese, lead) measured in hair and markers of cognition, attention, and behavior among 222 6-12 year old children who participated in a 2009-2010 neurodevelopmental follow-up to the C8 Health Project. Using quantile-based g-computation we estimated the adjusted overall metal mixture effect ψ (95 % CI) as the change in outcome per decile increase in all metals in the mixture. Hair metal levels varied by metal, with cadmium being lowest (median 0.007, interquartile range (IQR) 0.013 μg/g) and lead the highest concentration (median 0.152, IQR 0.252 μg/g). Children's cognitive skills and development, attention/impulsivity, and behavior were all close to standardized population means. Each decile increase in all metals was associated with a Full Scale IQ reduction of 1.01 points (95 % confidence interval (CI) -1.88, -0.15) and Verbal IQ reduction of 1.11 points (95 % CI -1.97, -0.25), adjusted for child age, sex, secondhand smoke exposure, HOME score, maternal education, maternal IQ, and examiner. Maternal report of ADHD-like behaviors and executive functioning also showed adverse associations with the metal mixture. Our findings suggest that similar to exposure during prenatal and early childhood periods, recent exposure to metals during middle childhood is associated with adverse neurodevelopmental consequences. Middle childhood may also be a developmental window of susceptibility to the negative consequences of exposure to environmental neurotoxicants.

In the United States, racial/ethnic minoritized groups experience worse sleep than non-Hispanic Whites (nHW), but less is known about pregnant people. This is a key consideration since poor sleep during pregnancy is common and associated with increased risk of adverse perinatal outcomes. This study reports the prevalence of subjective sleep measures in a multi-racial/ethnic pregnant population from the Environmental influences on Child Health Outcomes (ECHO) program. Participants' self-reported race and ethnicity were grouped into: nHW, non-Hispanic Black/African American (nHB/AA), Hispanic, non-Hispanic Asian (nHA). Analyses examined trimester-specific (first (T1), second (T2), third (T3)) nocturnal sleep duration, quality, and disturbances (Pittsburgh Sleep Quality Index and ECHO maternal sleep health questionnaire). Linear or multinomial regressions estimated the associations between race/ethnicity and each sleep domain by trimester, controlling for body mass index and age, with nHW as reference group. We repeated analyses within maternal education strata. nHB/AA participants reported shorter sleep duration (T2: β = -0.55 [-0.80,-0.31]; T3: β = -0.65 [-0.99,-0.31]) and more sleep disturbances (T2: β = 1.92 [1.09,2.75]; T3: β = 1.41 [0.09,2.74]). Hispanic participants reported longer sleep duration (T1: β = 0.22 [0.00004,0.44]; T2: β = 0.61 [0.47,0.76]; T3: β = 0.46 [0.22,0.70]), better sleep quality (Reference group: Very good. Fairly good T1: OR = 0.48 [0.32,0.73], T2: OR = 0.36 [0.26,0.48], T3: OR = 0.31 [0.18,0.52]. Fairly bad T1: OR = 0.27 [0.16,0.44], T2: OR = 0.46 [0.31, 0.67], T3: OR = 0.31 [0.17,0.55]), and fewer sleep disturbances (T2: β = -0.5 [-1.0,-0.12]; T3: β = -1.21 [-2.07,-0.35]). Differences persisted within the high-SES subsample. Given the stark racial/ethnic disparities in perinatal outcomes and their associations with sleep health, further research is warranted to investigate the determinants of these disparities.

BACKGROUND AND AIMS/OBJECTIVE:Anti-tumour necrosis factor [anti-TNF] induced skin reactions are common adverse events in paediatric inflammatory bowel disease [IBD]. We aimed to report on outcomes of children with anti-TNF induced skin reactions who switched to ustekinumab [UST] vs. continued anti-TNF therapy. METHODS:Charts were reviewed for paediatric IBD patients with anti-TNF induced skin reactions. Skin reactions, including psoriasiform dermatitis [PD], were classified as mild or severe based on a severity score. Primary outcome was frequency of skin resolution at 6 months. Secondary outcomes were combined clinical remission and skin resolution at 6 months and skin resolution at latest follow-up. RESULTS:A total of 111/638 [17%] children ([85, 21%] infliximab [IFX]; [26, 11%] adalimumab [ADA]) developed skin reactions. Eighty [72%] had PD, 25 [23%] infections, and four [4%] alopecia areata; 71 [64%] continued anti-TNF; and 40 [36%] switched to UST. In all, 73 [66%] had severe reactions and were more likely to switch to UST than if mild (37 [51%] vs. 3 [8%]; p <0.0001). Switching to UST had a higher rate and odds of resolution (29 [73%] vs. 24 [34%]; p <0.0001; odds ratio [OR] = 19.7, 95% confidence interval [CI]: 5.6, 69.5; p <0.0001) and combined remission (21 [52%] vs. 22 [31%]; p = 0.03; OR = 8.5, 95% CI: 2.5, 28.4; p = 0.0005] vs. continuing anti-TNF at 6 months. CONCLUSIONS:Children who switched to UST after anti-TNF induced skin reactions were more likely to have improved outcomes than those who continued anti-TNF therapy. Future studies are needed to determine immune mechanisms of anti-TNF induced skin reactions and treatment response.

Groundbreaking insights into the origins of the human mind have been garnered through the study of eye movements in preverbal subjects who are unable to explain their thought processes. Developmental research has largely relied on in-lab testing with trained experimenters. This constraint provides a narrow window into infant cognition and impedes large-scale data collection in families from diverse socioeconomic, geographic, and cultural backgrounds. Here we introduce a new open-source methodology for automatically analyzing infant eye-tracking data collected on personal devices in the home. Using algorithms from computer vision, machine learning, and ecological psychology, we develop an online webcam-linked eye tracker (OWLET) that provides robust estimation of infants' point of gaze from smartphone and webcam recordings of infant assessments in the home. We validate OWLET in a large sample of 7-month-old infants (N = 127) tested remotely, using an established visual attention task. We show that this new method reliably estimates infants' point-of-gaze across a variety of contexts, including testing on both computers and mobile devices, and exhibits excellent external validity with parental-report measures of attention. Our platform fills a significant gap in current tools available for rapid online data collection and large-scale assessments of cognitive processes in infants. Remote assessment addresses the need for greater diversity and accessibility in human studies and may support the ecological validity of behavioral experiments. This constitutes a critical and timely advance in a core domain of developmental research and in psychological science more broadly.

The Brain Imaging Data Structure (BIDS) is a specification accompanied by a software ecosystem that was designed to create reproducible and automated workflows for processing neuroimaging data. BIDS Apps flexibly build workflows based on the metadata detected in a dataset. However, even BIDS valid metadata can include incorrect values or omissions that result in inconsistent processing across sessions. Additionally, in large-scale, heterogeneous neuroimaging datasets, hidden variability in metadata is difficult to detect and classify. To address these challenges, we created a Python-based software package titled "Curation of BIDS" (CuBIDS), which provides an intuitive workflow that helps users validate and manage the curation of their neuroimaging datasets. CuBIDS includes a robust implementation of BIDS validation that scales to large samples and incorporates DataLad--a version control software package for data--as an optional dependency to ensure reproducibility and provenance tracking throughout the entire curation process. CuBIDS provides tools to help users perform quality control on their images' metadata and identify unique combinations of imaging parameters. Users can then execute BIDS Apps on a subset of participants that represent the full range of acquisition parameters that are present, accelerating pipeline testing on large datasets.

OBJECTIVES/OBJECTIVE:We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation. DESIGN/METHODS:Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial. SETTING/METHODS:Five U.S. medical centers. PATIENTS/METHODS:Adults inpatients with severe COVID-19 disease and hyperinflammation. INTERVENTIONS/METHODS:Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo. MEASUREMENTS AND MAIN RESULTS/RESULTS:The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival ,frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively). CONCLUSIONS:Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

Maternal-fetal attachment (MFA), a woman's relationship with and affiliative behaviors toward her unborn child, has been linked to near-term infant physical and developmental outcomes. However, further longitudinal research is needed to understand whether the impact of MFA extends past the earliest years of life. The current study explored relationships between MFA and child socioemotional competence and behavior problems at age 3 and whether parenting stress mediated the association between MFA and child outcomes. Data were collected from 221 primarily Black/African-American mothers who completed a scale of MFA during pregnancy. Mothers reported on parenting stress at infant age 7 months and reported on child socioemotional competence and problem behaviors at child age 3 years. In path analyses, MFA was directly associated with child socioemotional competence at age 3 years, but an indirect association between MFA and socioemotional competence via parenting stress was not significant. We also observed a significant indirect association between lower MFA and child internalizing behavior problems via parenting stress that was related to maternal dissatisfaction regarding interactions with her child. Findings suggest that assessing MFA may serve as a means to identify dyads who would benefit from support to promote individual health outcomes.

OBJECTIVE:Racism is a public health crisis impacting children's mental health, yet mental health service systems are insufficiently focused on addressing racism. Moreover, a focus on interpersonal racism and on individual coping with the impacts of racism has been prioritized over addressing structural racism at the level of the service system and associated institutions. In this paper, we examine strategies to address structural racism via policies impacting children's mental health services. METHOD/METHODS:First, we identify and analyze federal and state policies focused on racism and mental health equity. Second, we evaluate areas of focus in these policies and discuss the evidence base informing their implementation. Finally, we provide recommendations for what states, counties, cities, and mental health systems can do to promote antiracist evidence-based practices in children's mental health. RESULTS:Our analysis highlights gaps and opportunities in the evidence base for policy implementation strategies including: mental health services for youth of color, interventions addressing interpersonal racism and bias in the mental health service system, interventions addressing structural racism, changes to provider licensure and license renewal, and development of the community health workforce. CONCLUSION/CONCLUSIONS:Recommendations are provided both within and across systems to catalyze broader systems transformation.