Faculty Bibliography

BACKGROUND:The association between adversity and psychopathology in adolescents and adults is characterized by equifinality. These associations, however, have not been assessed during early childhood when psychopathology first emerges. Defining adversity using both dimensional and cumulative risk approaches, we examined whether specific types of adversity are differentially associated with psychopathology in preschool-aged children. METHODS:Measures of threat, deprivation, and total adversities (i.e., cumulative risk) were calculated based on parent-reported information for 755 2- to 5-year old children recruited from pediatric primary care clinics. Logistic regression was used to estimate cross-sectional associations between type of adversity and anxiety, depression, ADHD, and behavioral disorder diagnoses. RESULTS:Threat and cumulative risk exhibited independent associations with psychopathology. Threat was strongly related to behavioral disorders. Cumulative risk was consistently related to all psychopathologies. CONCLUSIONS:Using mutually adjusted models, we identified differential associations between threat and psychopathology outcomes in preschool-aged children. This selectivity may reflect different pathways through which adversity increases the risk for psychopathology during this developmentally important period. As has been observed at other ages, a cumulative risk approach also effectively identified the cumulative impact of all forms of adversity on most forms of psychopathology during early childhood.

OBJECTIVE:Evaluating the impact of the Inversion Time (TI) on regional perfusion estimation in a pediatric cohort using Arterial Spin Labeling (ASL). MATERIALS AND METHODS/METHODS:Pulsed ASL (PASL) was acquired at 3 T both at TI 1500 ms and 2020 ms from twelve MRI-negative patients (age range 9-17 years). A volume of interest (VOIs) and a voxel-wise approach were employed to evaluate subject-specific TI-dependent Cerebral Blood Flow (CBF) differences, and grey matter CBF Z-score differences. A visual evaluation was also performed. RESULTS:CBF was higher for TI 1500 ms in the proximal territories of the arteries (PTAs) (e.g. insular cortex and basal ganglia - P < 0.01 and P < 0.05 from the VOI analysis, respectively), and for TI 2020 ms in the distal territories of the arteries (DTAs), including the watershed areas (e.g. posterior parietal and occipital cortex - P < 0.001 and P < 0.01 from the VOI analysis, respectively). Similar differences were also evident when analyzing patient-specific CBF Z-scores and at a visual inspection. CONCLUSIONS:TI influences ASL perfusion estimates with a region-dependent effect. The presence of intraluminal arterial signal in PTAs and the longer arterial transit time in the DTAs (including watershed areas) may account for the TI-dependent differences. Watershed areas exhibiting a lower perfusion signal at short TIs (~ 1500 ms) should not be misinterpreted as focal hypoperfused areas.

OBJECTIVE:To model children's mental health policy making dynamics and simulate the impacts of knowledge broker interventions. DATA SOURCES/METHODS:Primary data from surveys (n = 221) and interviews (n = 64) conducted in 2019-2021 with mental health agency (MHA) officials in state agencies. STUDY DESIGN/METHODS:A prototype agent-based model (ABM) was developed using the PARTE (Properties, Actions, Rules, Time, Environment) framework and informed through primary data collection. In each simulation, a policy is randomly generated (salience weights: cost, contextual alignment, and strength of evidence) and discussed among agents. Agents are MHA officials and heterogenous in their properties (policy making power and network influence) and policy preferences (based on salience weights). Knowledge broker interventions add agents to the MHA social network who primarily focus on the policy's research evidence. DATA COLLECTION/EXTRACTION METHODS/METHODS:A sequential explanatory mixed method approach was used. Descriptive and regression analyses were used for the survey data and directed content analysis was used to code interview data. Triangulated results informed ABM development. In the ABM, policy makers with various degrees of decision influence interact in a scale-free network before and after knowledge broker interventions. Over time, each decides to support or oppose a policy proposal based on policy salience weights and their own properties and interactions. The main outcome is an agency-level decision based on policy maker support. Each intervention and baseline simulation runs 250 times across 50 timesteps. PRINCIPAL FINDINGS/RESULTS:Surveys and interviews revealed that barriers to research use could be addressed by knowledge brokers. Simulations indicated that policy decision outcomes varied by policy making context within agencies. CONCLUSIONS:This is the first application of ABM to evidence-informed mental health policy making focusing. Results suggest that the presence of knowledge brokers can: (1) influence consensus formation in MHAs, (2) accelerate policy decisions, and (3) increase the likelihood of evidence-informed policy adoption.

We developed a "gut-brain-axis questionnaire" (GBAQ) to obtain standardized person-specific "review of systems" data for microbiome-gut-brain-axis studies. Individual items were compared to PANSS symptom measures using dimensional, transdiagnostic and traditional categorical approaches.

PURPOSE: The prognosis for SHH-medulloblastoma (MB) patients with Li-Fraumeni syndrome (LFS) is poor. Due to lack of comprehensive data for these patients, it is challenging to establish effective therapeutic recommendations. We here describe the largest retrospective cohort of pediatric LFS SHH-MB patients to date and their clinical outcomes.
PATIENTS AND METHODS: N=31 patients with LFS SHH-MB were included in this retrospective multicenter study. TP53 variant type, clinical parameters including treatment modalities, event-free survival (EFS) and overall survival (OS), as well as recurrence patterns and incidence of secondary neoplasms, were evaluated.
RESULT(S): All LFS-MBs were classified as SHH subgroup, in 30/31 cases based on DNA methylation analysis. The majority of constitutional TP53 variants (72%) represented missense variants, and all except two truncating variants were located within the DNA-binding domain. 54% were large cell anaplastic, 69% gross totally resected and 81% had M0 status. The 2-(y)ear and 5-(y)ear EFS were 26% and 8,8%, respectively, and 2y- and 5y-OS 40% and 12%. Patients who received post-operative radiotherapy (RT) followed by chemotherapy (CT) showed significantly better outcomes (2y-EFS:43%) compared to patients who received CT before RT (30%) (p<0.05). The 2y-EFS and 2y-OS were similar when treated with protocols including high-dose chemotherapy (EFS:22%, OS:44%) compared to patients treated with maintenance-type chemotherapy (EFS:31%, OS:45%). Recurrence occurred in 73.3% of cases independent of resection or M-status, typically within the radiation field (75% of RT-treated patients). Secondary malignancies developed in 12.5% and were cause of death in all affected patients.
CONCLUSION(S): Patients with LFS-MBs have a dismal prognosis. This retrospective study suggests that upfront RT may increase EFS, while intensive therapeutic approaches including high-dose chemotherapy did not translate into increased survival of this patient group. To improve outcomes of LFS-MB patients, prospective collection of clinical data and development of treatment guidelines are required

Anxiety has been associated with reliance on reactive (stimulus-driven/reflexive) control strategies in response to conflict. However, this conclusion rests primarily on indirect evidence. Few studies utilize tasks that dissociate the use of reactive ('just in time') vs. proactive (anticipatory/preparatory) cognitive control strategies in response to conflict, and none examine children diagnosed with anxiety. The current study utilizes the AX-CPT, which dissociates these two types of cognitive control, to examine cognitive control in youth (ages 8-18) with and without an anxiety diagnosis (n = 56). Results illustrate that planful behavior, consistent with using a proactive strategy, varies by both age and anxiety symptoms. Young children (ages 8-12 years) with high anxiety exhibit significantly less planful behavior than similarly-aged children with low anxiety. These findings highlight the importance of considering how maturation influences relations between anxiety and performance on cognitive-control tasks and have implications for understanding the pathophysiology of anxiety in children.

OBJECTIVE/UNASSIGNED:Autism spectrum disorder (ASD) is heritable, and younger siblings of ASD probands are at higher likelihood of developing ASD themselves. Prospective MRI studies of siblings report that atypical brain development precedes ASD diagnosis, although the link between brain maturation and genetic factors is unclear. Given that familial recurrence of ASD is predicted by higher levels of ASD traits in the proband, the authors investigated associations between proband ASD traits and brain development among younger siblings. METHODS/UNASSIGNED:In a sample of 384 proband-sibling pairs (89 pairs concordant for ASD), the authors examined associations between proband ASD traits and sibling brain development at 6, 12, and 24 months in key MRI phenotypes: total cerebral volume, cortical surface area, extra-axial cerebrospinal fluid, occipital cortical surface area, and splenium white matter microstructure. Results from primary analyses led the authors to implement a data-driven approach using functional connectivity MRI at 6 months. RESULTS/UNASSIGNED:Greater levels of proband ASD traits were associated with larger total cerebral volume and surface area and larger surface area and reduced white matter integrity in components of the visual system in siblings who developed ASD. This aligned with weaker functional connectivity between several networks and the visual system among all siblings during infancy. CONCLUSIONS/UNASSIGNED:The findings provide evidence that specific early brain MRI phenotypes of ASD reflect quantitative variation in familial ASD traits. Multimodal anatomical and functional convergence on cortical regions, fiber pathways, and functional networks involved in visual processing suggest that inherited liability has a role in shaping the prodromal development of visual circuitry in ASD.

Child welfare (CW) agencies are charged with ensuring children's safety; when children live with families impacted by intimate partner violence (IPV), this task can be complex. To better understand how U.S. CW agencies identify and make decisions about child maltreatment (CM) in the presence of IPV, this mixed-methods study used national data (N = 248,654) to investigate whether IPV was more likely to be documented as co-occurring with certain types of CM. This study also explored the intersection of IPV and CM using 19 semi-structured interviews with child welfare stakeholders to gain insight into the mechanisms underpinning reporting processes. Multinomial logistical regression showed that after controlling for other risk factors, children living in a household with IPV were more likely to be determined to be physically abused and emotionally maltreated than neglected, and less likely to be determined to be sexually abused than neglected, compared with children who did not live in a household with IPV. Those children were also more likely to be determined to be emotionally maltreated than physically abused, and less likely to be determined to be sexually abused than physically abused, compared with children who did not live in a household with IPV (all results, p < .0001). Qualitative results revealed IPV and children's exposure to IPV may be categorized as different types of CM by CW agencies and staff, and that this categorization can vary by agency and staff level. Participants also described challenges to addressing IPV within CW systems. Findings suggest national CW data may obscure when IPV and CM co-occur versus when a given type of CM is serving as a proxy for the presence of or children's exposure to IPV, presenting challenges to interpreting child welfare data. Recommendations are presented to improve CW data accuracy and ensure the safety of children and families impacted by IPV.

SUMMARY/CONCLUSIONS:Poor research integrity is increasingly recognised as a serious problem in science. We outline some evidence for this claim and introduce the Royal College of Psychiatrists (RCPsych) journals' Research Integrity Group, which has been created to address this problem.