Faculty Bibliography

Parental reflective functioning (PRF) refers to a parent's ability to understand their own and their child's mental states and connect them to behaviors. This longitudinal study evaluated (1) associations among prenatal PRF, using the Pregnancy Interview, demographics, prenatal maternal depressive symptoms, and maternal-fetal attachment and (2) whether prenatal PRF predicted parenting quality assessed during unstructured and challenging mother-child interaction tasks beyond infancy, after controlling for cumulative risk. Data were collected in an urban community sample of women in the midwestern US. Prenatal PRF was positively associated with maternal educational attainment and negatively associated with cumulative demographic risk, but not with depressive symptoms or maternal-fetal attachment. Controlling for cumulative risk, hierarchical regressions showed that prenatal PRF was the sole significant predictor of positive parenting at 36 months, observed during a challenging teaching task but not during free play. Prenatal PRF did not predict negative parenting. These patterns persisted when analyses were repeated within a subsample of Black mothers, with PRF again being the sole significant predictor of positive parenting. Further attention to cultural variations in PRF and parenting in future research is warranted.

Household chaos has been shown to be an important predictor across multiple domains of children's development, with both direct associations and indirect associations through changes in parenting practices. Yet, little is known about these associations among immigrant families. Data from the Children, Community, and Caregivers (C3) Study of the larger Together Growing Strong place-based initiative among predominantly Chinese and Latine immigrant families in the Sunset Park neighborhood of Brooklyn, New York were used to examine cross-sectional associations between household chaos and child behavior and receptive vocabulary at child ages 4 and 6 (N = 187). The STROBE checklist for cross-sectional research was adhered to. Linear regression models were used to examine unique contributions of variables, as well as structural equation modeling to examine mediation through parenting stress. As a supplemental exploratory analysis, differences in associations between household chaos and child behavior and language by race/ethnicity were further examined. There were significant positive associations between household chaos and parental reports of children's problem behavior (β = 0.21, 95% CI [0.07-0.35]) and significant negative associations between household chaos and direct assessments of children's receptive vocabulary (β=-0.21, 95% CI [-0.37 - -0.04]). Further, there were indirect associations of household chaos through parenting stress for child problem behavior only (β = 0.11, 95% CI [0.05-0.17]). The results for the main linear regression models and mediation models were primarily driven by Chinese families. Implications for predictors of child development in immigrant populations and the enduring salience of household chaos are discussed.

Individuals with Alzheimer's disease (AD) have an increased incidence of seizures, which worsen cognitive decline. Using a transgenic mouse model of AD neuropathology that exhibits spontaneous seizures, we previously found that seizure activity stimulates and accelerates depletion of the hippocampal neural stem cell (NSC) pool, which was associated with deficits in neurogenesis-dependent spatial discrimination. However, the precise molecular mechanisms that drive seizure-induced activation and depletion of NSCs are unclear. Here, using mice of both sexes, we performed RNA-sequencing on the hippocampal dentate gyrus and identified differentially-expressed regulators of neurogenesis in the Wnt signaling pathway that regulates many aspects of cell proliferation. We found that the expression of sFRP3, a Wnt signaling inhibitor, is altered in a seizure-dependent manner and might be regulated by ΔFosB, a seizure-induced transcription factor. Increasing sFRP3 expression prevented NSC depletion and improved spatial discrimination, suggesting that the loss of sFRP3 might mediate seizure-driven impairment in cognition in AD model mice, and perhaps also in AD.Significance statement There is increased incidence of seizures in individuals with Alzheimer's disease (AD), but it is unclear how seizures contribute to cognitive decline. Here, we uncover a molecular mechanism by which seizures in AD induce expression of a long-lasting transcription factor in the hippocampal dentate gyrus that suppresses expression of sFRP3, an inhibitor of neural stem cell division, accelerating the depletion of a finite pool of neural stem cells and dysregulating adult hippocampal neurogenesis. We found that restoring sFRP3 expression prevents accelerated use and depletion of neural stem cells and improves performance in an adult neurogenesis-dependent cognitive task. Our findings have implications for AD, epilepsy, and other neurological disorders that are accompanied by seizures.

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in N = 166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in low motion whole-brain intrinsic functional connectivity (iFC) and dimensional measures of autism and ADHD symptoms indexed by clinician-based observation and parent interview, respectively. Additionally, we explored their linked gene expression patterns in silico. Whole-brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes primarily on the left hemisphere: the middle frontal gyrus of the frontoparietal network and the posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD ratings. Results from secondary segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC for autism symptom severity across diagnoses. No statistically significant brain-behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to: (i) have greater rate of variance in autism and ADHD, and (ii) be involved in neuron projections, suggesting shared genetic mechanisms for this specific brain-clinical phenotype. These findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically-defined and observation-based phenomena to shared presentations at the macroscale circuit- and genomic-levels across diagnoses.

Our objective was to examine the role of structural racism and economic disadvantage in perinatal health inequities using the Environmental influences on Child Health Outcomes Cohort. Participants' addresses were linked to area-level measures of life expectancy, education, unemployment, health insurance, jail rate, segregation, and housing cost burden. We created absolute measures to represent economic disadvantage and relative measures comparing values for Black or Latinx people to White people in the same area to represent structural racism. We used quantile G-computation to estimate the effects of a one-quartile increase in all exposures simultaneously on fetal growth and gestational age measures. A one-quartile increase in economic disadvantage was associated with a reduction in birthweight [(-25.65 grams, 95% CI (-45.83, -5.48)], but not gestational age [-0.02 weeks, 95% CI (-0.13, 0.09)]. With a one-quartile increase in Latinx-White structural racism, we observed reductions in birthweight [-80.83, 95% CI (-143.42, -18.23)) among Latinx participants. A one-quartile increase in Black-White structural racism was weakly associated with lower birthweight among Black participants [-15.70, 95% CI (-82.89, 51.48)] but was associated with higher birthweight among White participants [57.47, 95% CI (13.26, 101.67)]. Our findings suggest co-occurring forms of structural inequity likely influence racialized disparities in fetal growth outcomes.

The transition from Child and Adolescent (CAMHS) to Adult Mental Health Services (AMHS) can be challenging. Drawing on the sample of the European MILESTONE project, we explored changes in clinical profiles and treatment outcomes in adolescents transitioning to AMHS over two years, focusing on different pharmacological treatment patterns. The sample (N = 690; mean age: 17.7 years; SD = 0.29) was categorised into three groups based on medication patterns: continuous (Group 1), intermittent (Group 2), and never medicated (Group 3). Participants underwent four evaluations over two years using tools measuring psychopathology and functioning, including the Health of the Nation Outcome Scale for Child and Adolescents (HoNOSCA) and ASEBA Battery. We employed repeated-measures models to analyse clinical rating changes and a two-way mixed ANOVA to assess interaction between time and groups. Group 3 had significantly lower mean HoNOSCA ratings than Groups 1 and 2 (p < 0.001), indicating better mental health. By the last time point (T4), the factors associated with a reduced risk of severe illness included an improvement in the risk of suicide attempts (p = 0.038), enhanced everyday functional skills (p = 0.008), higher quality of life (p = 0.001), and being male (p = 0.020). The ASEBA Battery showed Group 1 had more internalising symptoms, while Group 2 had more externalising symptoms than Group 3. During the transition from CAMHS to AMHS, continuous medication was associated with higher symptom severity than intermittent or no pharmacological treatment. This may reflect either a more severe initial symptomatology requiring sustained pharmacotherapy or a medication-related paradox, whereby symptoms persist or intensify owing to treatment resistance or side effects. TRIAL REGISTRATION: "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

In this Personal View, we address key questions to support evidence-based prevention and management of psychotic symptoms that might occur during ADHD pharmacotherapy. We begin by examining evidence showing a significantly increased occurrence of psychotic disorders in individuals with ADHD, independent of ADHD medications (pooled relative risk, odds ratio, or hazard ratio=4·74, 95% CI 4·11-5·46). We then examine whether ADHD medications play a causal role, noting that current evidence does not support such a causal link, at least for methylphenidate. We explore how vulnerability to psychosis varies across individuals with ADHD. Regarding the different steps involved in prescribing ADHD medications, we discuss the importance of balancing potential risks-such as emergence of psychotic symptoms-against the demonstrated benefits of pharmacological treatment for ADHD. Next, we present strategies for screening individuals for vulnerability to psychosis before initiating ADHD medication. We then offer guidance on the clinical management of psychotic symptoms that might arise during ADHD pharmacotherapy, including considerations of dosage and medication type. Finally, we identify key research priorities in this area. Overall, this paper provides an empirical framework, grounded in evidence and clinical practice, to guide the next steps in the field.