Faculty Bibliography

Trajectories of age-related neurocognitive decline are nonuniform, and are impacted by numerous environmental and physiological factors. Earlier life phases set the stage for later life neurocognitive function, with midlife marking a critical transition characterized by increasing variability in cognitive, affective, and physiological functioning. Despite its importance, this turbulent period remains underrepresented in open neuroimaging data resources. To address this gap, the Nathan Kline Institute - Rockland Sample (NKI-RS) created 'Mapping Interindividual Variation in the Aging Connectome' (MIVAC), an openly shared, multimodal dataset designed to map brain aging trajectories beginning in midlife and assess the influence of key modifiable factors linked to dementia prevention such as cardiorespiratory fitness, sleep, and mood. This longitudinal investigation includes 348 community-ascertained participants aged 38 to 71 years at baseline, with 219 participants completing 3 annual timepoints. Data collection incorporated deep phenotyping, including detailed assessment of cognitive, behavioral, medical, and cardiorespiratory fitness domains, to compliment multimodal neuroimaging (resting-state fMRI, diffusion MRI, morphometric MRI, and arterial spin labeling) and biospecimen collection. The protocol harmonizes with prior NKI-RS sub studies, enabling lifespan cross-sectional or longitudinal questions, while incorporating age-specific considerations for cognitive and neural aging. The full dataset is openly available.

Traumatic experiences in early childhood trauma are increasingly recognized as a major public health concern, with infants and toddlers particularly vulnerable because of their rapidly developing brains. Repeated or prolonged exposure to trauma is shown to disrupt neurodevelopment, particularly in brain regions responsible for emotion regulation, executive functioning, stress-response processing, and memory. While it is well established that early childhood trauma negatively impacts social, emotional, and cognitive development, growing evidence demonstrates that early trauma also contributes to long term physical health challenges. In young children, trauma frequently manifests through physiological and bodily symptoms due to their limited capacity to communicate psychological distress. As a result, trauma may present as heightened arousal, somatic issues, sleep disturbances, and feeding difficulties. These concerns are commonly encountered in pediatric healthcare settings, though they may be overlooked or misattributed because of their overlap with other medical conditions. Early childhood represents a critical time for identification and intervention. Pediatric providers are uniquely positioned to identify these early physiological signs of trauma in young children because of their frequent touch points with families. A greater understanding of the manifestations of early trauma in health is needed to improve diagnostic accuracy and promote early intervention. In this paper, we review the effects of early trauma on the physical health of infants and toddlers, highlighting the critical role of pediatric providers in early identification and the integration of trauma-informed care within pediatric settings.

This study examines for whom and how Organizational Skills Training-Tier 2 (OST-T2, Nissley-Tsiopinis et al., 2024) works for students in grades 3 to 5 with organization, time management, and planning (OTMP) difficulties. The study: (1) investigates subgroup differences for the effect of OST-T2 on student homework and academic performance at post-intervention (about 14 weeks), short-term (about 22 weeks) and long-term follow-up (about 55 weeks); and (2) examines whether improvements in student OTMP skills at 14 weeks mediate the effect of OST-T2 on academic and homework performance at 22 weeks. The study used a cluster-randomized design with 22 schools; 182 students in moderation analyses and 133 in mediation analyses. Subgroup-defining variables were: (a) likely diagnosis of ADHD, (b) caregiver-reported child anxiety, (c) severity of baseline OTMP and homework problems, and (d) family socioeconomic level. Findings suggested that OST-T2 is more effective among children with higher anxiety levels as reported by caregivers. The difference in change scores between the high and low anxiety groups on the caregiver-rated metric of OTMP and homework problems was -0.76 (Cohen's d) at post-treatment (95% CI = -0.12, -1.21, p = .021), -0.66 at 22 weeks (95% CI = -0.08, -1.09, p = .017), and - 0.55 at 55 weeks (95% CI = -0.07, -1.03, p = .026). The analyses generally did not detect subgroup effects based on ADHD diagnostic status and families differing in socioeconomic levels. Results also suggested improvements in OTMP skills in response to OST-T2 are likely to signal downstream impact on student homework performance; estimated average causal mediation effect was -0.66 (95% CI = -1.27, -0.19, p < .001), whereas the average direct effect was only -0.07. Additional longitudinal research with larger samples on predefined subgroups is needed.

INTRODUCTION/BACKGROUND:Serotonin (5-hydroxytryptamine [5-HT]) plays an important role in early development, and fetal 5-HT has been reported to arise from placental and maternal sources. Previous human studies have established an association between maternal 5-HT levels and neurodevelopmental outcomes in populations with autism. In this study, we analyze umbilical cord blood and placental 5-HT levels at birth to further investigate the relationship of gestational 5-HT levels with birth outcomes and offspring cognitive development. METHODS:Participants were enrolled in the Safe Passage Study conducted by the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network. Infant cord blood and placental samples were collected postdelivery, and 5-HT levels were measured using high-performance liquid chromatography-fluorometric analysis. The Mullen Scales of Early Learning (MSEL) assessed child development at 12 months. Associations between 5-HT levels and birth outcomes or developmental outcomes were assessed using linear regression models. RESULTS:No significant association was found between cord blood (n = 418) and placental (n = 89) 5-HT levels. Preterm birth was associated with lower cord blood 5-HT levels, and increasing gestational age among full-term infants was associated with higher cord blood 5-HT levels. Cord blood 5-HT was significantly associated with the Mullen Scales of Early Learning Composite Score, and follow-up analyses revealed a significant association between cord blood 5-HT and fine motor skills. No association was found between placental 5-HT and the Mullen composite score. CONCLUSION/CONCLUSIONS:To our knowledge, this study is the first to evaluate the relationship between placental 5-HT levels and cord blood 5-HT levels at birth. The lack of association suggests that cord blood 5-HT levels are likely to be a better index of fetal 5-HT exposure. Associations between cord blood 5-HT and child cognitive development are consistent with previous studies showing an association between maternal 5-HT levels and neurodevelopmental trajectories. Further research is needed to better characterize these relationships and to elucidate the distinct contributions of maternal, placental, and fetal 5-HT sources across developmental time points.

OBJECTIVE/BACKGROUND/OBJECTIVE:Attention-Deficit/Hyperactivity Disorder (ADHD) is common in children. Many children with ADHD have chronic insomnia, which is associated with negative outcomes for the child and family and can worsen ADHD symptoms. Behavioural sleep interventions can be effective for children with ADHD and are the recommended first-line approach to management. However, many parents/carers may not have access to, or struggle to implement, interventions in practice. This study explored parents/carers views and experiences of: 1) behavioural sleep management strategies, 2) help-seeking for managing sleep problems and 3) perceptions about a potential digital sleep guide for managing sleep problems. PATIENTS/METHODS/METHODS:A qualitative study using semi-structured interviews of parents/carers of children with ADHD/ADHD traits and chronic insomnia symptoms (CIS). Participants were recruited via social media and purposively sampled for diverse characteristics. Interviews were conducted by telephone/videocall, recorded and transcribed verbatim. Data were analysed using inductive thematic analysis. RESULTS:Eighteen parents/carers took part; two themes and six subthemes were developed. Despite valuing behavioural sleep strategies, parents/carers noted many challenges to engaging with them, including perceiving these strategies to be both ineffective for children with ADHD and not easy to implement in the real world. They described that tiredness, exhaustion, ADHD symptoms and challenging behaviour make parent engagement with strategies difficult. Parents/carers welcomed digital support in principle, particularly because they perceived health professional support to be lacking. However, they noted that digital interventions must address their key support needs regarding flexibility, realistic expectations and a pragmatic approach, as well as comradeship, support and testimonials from other parents/carers. CONCLUSION/CONCLUSIONS:Tailored but flexible support and reassurance are necessary for parents/carers of children with ADHD and CIS. Digital support must validate parent/carer experiences and include experiences from other parents/carers.

OBJECTIVE/UNASSIGNED:Obsessive-compulsive disorder (OCD) is one of the common mental disorders globally. However, there are limited studies on the prevalence of OCD and four other disorders categorized under obsessive-compulsive and related disorders, namely, hoarding disorder, excoriation disorder, body dysmorphic disorder, and trichotillomania. The authors sought to fill the epidemiological gap in the literature. METHODS/UNASSIGNED:criteria, were included. A Bayesian hierarchical linear mixed model was used to estimate the lifetime prevalence of OCD at the global, regional, and national levels, with estimates reported with 95% credible intervals. The authors examined the association between OCD prevalence and the Socio-demographic Index (SDI), and estimated age-specific point prevalence of OCD. RESULTS/UNASSIGNED:criteria. Lifetime prevalence of OCD was negatively correlated with SDI, indicating lower prevalence estimates in countries with higher SDI. The age-specific prevalence of OCD increased sharply in the teen years and peaked in the late 20s to early 30s. Point prevalence ranged across studies from 0.98% to 5.81% for hoarding disorder, from 2.33% to 7.68% for excoriation disorder, from 0.44% to 15.21% for body dysmorphic disorder, and from 0.0% to 2.12% for trichotillomania. CONCLUSIONS/UNASSIGNED:This study estimated the global prevalence of OCD according to diagnostic criteria, underscoring the role of diagnostic definitions in shaping epidemiological understanding.

AIMS/UNASSIGNED:Proximal junctional kyphosis (PJK) remains a major complication after surgery for adult spinal deformity (ASD). While postoperative alignment is a recognized modifiable risk factor, objective methods for selecting the upper instrumented vertebra (UIV), a key modifiable factor, are lacking. We aimed to determine whether preoperative sagittal alignment, specifically cervicothoracic alignment, predicts the risk of PJK, and whether this risk can be mitigated by UIV selection, focusing on factors available at the time of surgical planning. METHODS/UNASSIGNED:From a multicentre, prospective ASD registry, we identified patients who had undergone fusion to the sacrum or pelvis and had an upper (T1-T5) or lower thoracic (T9-L1) UIV, with a two-year or more radiological follow-up, excluding those with a previous fusion over more than four levels. The primary outcome was PJK within two years. Multivariable logistic regression modelled the risk of PJK by UIV region, preoperative C2-T9 pelvic angle (PA), age, sex, and pelvic incidence, testing for interaction between UIV region and C2-T9 PA. Adjusted absolute risk reduction (ARR) and number needed to be exposed (NNEB) were calculated. Multivariable linear regression estimated two-year patient-reported outcome measures, adjusting for baseline scores, age, UIV, and PJK. RESULTS/UNASSIGNED:A total of 627 patients across 20 centres were included (median age 66 years (IQR 59 to 70); 483 (77%) female). The UIV was lower thoracic in 380 (61%) and upper thoracic in 247 (39%) patients. PJK occurred in 149 (39%) lower thoracic and 38 (15%) upper thoracic UIV patients. There was a significant interaction (p = 0.028) between preoperative C2-T9 PA and UIV region. At a preoperative C2-T9 PA of 14° (cohort median), an upper thoracic UIV had an adjusted ARR of 36% and NNEB was 2.8. Females had an adjusted odds ratio of 1.62 (95% CI 1.03 to 2.59; p = 0.042) for PJK. CONCLUSION/UNASSIGNED:Worse preoperative sagittal malalignment, measured by C2-T9 PA, was associated with a higher risk of PJK and depended on UIV region. An upper thoracic UIV in patients with high preoperative C2-T9 PA may reduce PJK.

OBJECTIVE:To evaluate cannabidiol (CBD) in pediatric patients with autism spectrum disorder (ASD), fluent verbal language and an estimated full-scale IQ of 80 or above. BACKGROUND:Preliminary evidence suggests CBD may ameliorate challenges associated with ASD. Whether CBD benefits pediatric ASD without accompanying intellectual or language impairment remains unknown. METHODS:, 100 mg/mL) at 3, 6, or 9 mg/kg/day using a Bayesian optimal interval dosing design. The primary endpoint was the CBD dose associated with the highest response rate (i.e., Clinical Global Impression Scale-Improvement [CGI-I] score = 1 or 2) on a target symptom domain designated individually based on informant report, standardized scales, and clinical observation. Secondary endpoints were effect sizes of changes from baseline in measures assessing ASD core and associated symptoms, and global functioning. Adverse events (AEs) were assessed weekly. Plasma CBD levels and clinical labs were obtained at the final visit. RESULTS:= 1.36, 95% CI [0.78-1.93]).Of 222 reported AEs, 27 unique AEs were considered treatment-related. Most AEs (93%) were mild and expected (82%); none was severe. The most frequent related AEs were increased salivation (30%), increased sleep duration (39%), sleepiness/sedation (26%), increased dream activity (35%), and polyuria (22%). Vital signs, physical exams, weight, liver function tests, and complete blood counts were unaffected. CBD plasma levels did not correlate with response. CONCLUSIONS:In this preliminary study, CBD was well tolerated; AEs were mild-moderate. Mean SRS2-T and subscores decreased significantly with large effect sizes, shifting from the severe to the moderate range. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier NCT03900923.