Faculty Bibliography

Individuals with Down syndrome (DS) are at risk for early-onset Alzheimer's disease (AD), marked by neurodegeneration in hippocampal and basal forebrain circuits. Early-life interventions offer therapeutic potential, including maternal choline supplementation (MCS). MCS improves cognitive outcomes and neuroplasticity in rodent models of neurodevelopmental and neurodegenerative disorders, yet cell-type specific molecular effects remain unknown. We investigated the effect of MCS upon the onset of septohippocampal degeneration at 6 months of age in the Ts65Dn mouse model of DS/AD. Using laser capture microdissection and single population RNA-sequencing, transcriptomic changes were profiled within hippocampal CA1 and CA3 pyramidal neurons and dentate gyrus granule cells comparing trisomic and disomic offspring. Bioinformatic analysis revealed MCS-mediated downregulation of apoptotic pathways and upregulation of cognition-related functions across all populations, alongside cell-specific responses. These findings highlight MCS as a promising strategy for modulating disease-relevant pathways in a hippocampal cell-type-specific manner during early neurodegeneration in DS/AD.

Exposure to trauma is common and frequently overlooked in behaviorally dysregulated youth. Common trauma-related symptoms, such as exaggerated startle responses, dissociative episodes, and irritability, may resemble behavioral dysregulation. These responses may not be recognized as being related to trauma. As a result, traumatized young people are often misdiagnosed and treated with antipsychotics. Trauma-informed care in health care settings, which includes systematic screening, staff training, trauma skills groups, and ongoing monitoring, is one way of addressing the effects of trauma and ensuring that young people receive access to the evidence-based care they deserve.

Trauma exposure in children and adolescents is a significant public health concern due to its profound impact on mental health and development. This study explores the complexities of trauma in youth, including the differentiation between trauma exposure and posttraumatic stress disorder, and the long-term effects of adverse childhood experiences. The study discusses the risks and benefits of polypharmacy in treating complex trauma and comorbid conditions in youth. Given the current gaps in research, the study emphasizes the need for comprehensive, individualized treatment plans that integrate psychotherapy, pharmacologic interventions, and psychosocial support to foster resilience and improve outcomes for trauma-exposed youth.

OBJECTIVE:Childhood inhibited temperament (cIT) is associated with an increased risk for developing internalizing psychopathology. Neurobiological characteristics identified by structural magnetic resonance imaging (MRI) may elucidate the neural substrates for cIT, but studies are scarce and often focus on particular regions of interest. Moreover, current findings lack replication. This pre-registered analysis from the ENIGMA-Anxiety Working Group examined structural brain characteristics associated with cIT using a comprehensive whole-brain approach. METHOD/METHODS:Temperament assessments (behavioral observations, parental/teacher reports or self-reports on cIT before age 13) and MRI-data (age at scan: 6-25 years) from international research sites (Europe, North America, South America) were pooled for mega-analysis. Following image processing and quality control, associations between cIT and brain structure were examined in 3,803 participants. Subcortical volumes, cortical thickness and surface area (main analyses) and detailed subcortical characteristics (e.g. subnuclei, subfields, partial volume effects; exploratory analyses) were considered. RESULTS:= 0.029) in youth with parental/teacher reports on cIT-levels. Exploratory analyses revealed findings in hippocampus, putamen and caudate, but most did not survive statistical correction for multiple testing. CONCLUSION/CONCLUSIONS:This mega-analysis found no consistent associations between cIT and regional brain structure, although the role of parietal regions warrants further investigation. Future studies should consider brain function in cIT, preferably using longitudinal designs.

Currently, the identification of individuals experiencing suicidal thoughts and behaviours (STBs) rely predominantly on self-report. Previous research on children and young people highlighted an association between difficulties in arousal regulation (reflected, for example, in reduced heart rate variability and altered electrodermal activity patterns) and STBs, but this has not been meta-analytically explored in adults. This systematic review and meta-analysis aimed to quantify the association between STBs and markers of autonomic functioning/regulation in adults. Based on a pre-registered protocol (PROSPERO CRD42024596886), we searched PubMed/MEDLINE, Embase, PsycINFO and Web of Science until 2^nd August 2025 for empirical studies assessing the association between measures of autonomic functioning and/or regulation and STBs in adults. Quality of cross-sectional and cohort studies was assessed through the Newcastle-Ottawa Scale. Pooled effect sizes (Hedge's g) were estimated with random-effects meta-analytic models in R. Out of 2,726 articles screened, 40 studies were included in the systematic review, and 22 in the meta-analyses (6,290 individuals, 28% with STBs). We found reduced heart rate variability in adults with STBs (g = -0.2469, p = 0.0069) but no significant associations between electrodermal activity patterns and STBs (g = -0.2563, p = 0.3953). Our results highlight the connection between reduced cardiac regulation and STBs, providing a rationale for further exploration of cardiac regulation as a potential objective marker for assessing and monitoring STBs in adults. Further research is warranted to understand how these markers can be used in clinical practice to assess and support the management of suicide risk in adults.

OBJECTIVE:To identify optimal strategies to integrate early relational health (ERH) programs in pediatric primary care (PPC) and to describe the development of a best practices toolkit to provide guidance and useful tools that clinicians can use to navigate this process. METHODS:A two-phased approach to develop, assess, and refine a best practices toolkit for the integration of multiple ERH programs in PPC through a modified Delphi process. Phase One included identification and assessment around barriers to ERH program integration and strategies to address them through surveys and focus groups of PPC clinics nationwide. Phase Two then utilized the identified barriers and strategies from Phase One to create a toolkit of best practices on integrating ERH programs in PPC that included two rounds of revision for a final version. RESULTS:126 PPC personnel from 44 clinics nationwide completed the Phase One survey, with respondents reporting many notable strengths and challenges to ERH program integration. 18 survey participants also participated in follow-up focus groups, which reiterated the strengths and challenges found in the surveys. An initial toolkit was then drafted, and experts provided qualitative, free-response feedback around clarity and presentation. Further improvement was made to create the final toolkit, which was rated highly useful and important, though slightly less feasible, by practitioners using formal feedback questions. CONCLUSION/CONCLUSIONS:This study employed a modified Delphi process to create a consensus-based best practices toolkit for integrating multiple ERH programs in PPC to help meet the heterogeneous needs of families to promote optimal child development.

OBJECTIVE/UNASSIGNED:Assessing suicide risk among children is complex, in part due to their developmental differences in identifying, recalling, and verbally describing internal states, alongside cultural differences in how distress is experienced. This study aimed to identify expressions of distress around suicide ideation or attempts through body mapping, a qualitative technique that facilitates both visual and verbal expressions. METHOD/UNASSIGNED: = 16). Children completed the Childhood Suicide Ideation Interview, which included semi-structured questions about their suicide ideation and/or attempt and a body mapping activity, where children illustrated and described their thoughts, feelings, body sensations, and social connections surrounding their suicidal crisis on a printed body silhouette. RESULTS/UNASSIGNED:Analyses conducted with Anthropac yielded 94 expressions of distress. The congruence in overall experiences across children was low (24%), yet specific somatic experiences like "shaking" (70%), "pain" (43%), and "dizziness" (39%) were prevalent. Other frequent experiences included "sad" (48%), "passive suicide ideation" (43%), and "thoughts about family" (39%). CONCLUSIONS/UNASSIGNED:Body mapping was a valuable tool for uncovering unique expressions of distress among ethnoracially diverse children. Somatic expressions, often overlooked in risk assessments, were prominent. Ours and similar studies have the potential to inform the design of culturally and developmentally responsive risk assessment tools and safety planning protocols.