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.

BACKGROUND:Sex differences in adolescent mental disorders are well documented, but less is known about how these differences evolve during the transition to adulthood, particularly during the shift from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS), a critical period marked by vulnerability to discontinuity of care. OBJECTIVE:To examine sex-specific differences in psychiatric symptom profiles and clinical trajectories during the CAMHS-AMHS transition using data from the European MILESTONE project, a 2-year longitudinal study. METHODS:A cohort of 1004 adolescents (aged 17-19) in CAMHS was assessed at baseline (T1), 9 months (T2), 15 months (T3) and 24 months (T4). Measures included the Child Behavior Checklist/Adult Behavior Checklist, Health of the Nation Outcome Scales for Children and Adolescents, and the Specific Level of Functioning Scale. Multilevel modelling included sex, diagnosis and time point as covariates, testing three-way interactions for differential trajectories. FINDINGS/RESULTS:Males showed higher symptom severity and impairment across measures, particularly in anxiety/somatic/trauma, eating disorder/obsessive-compulsive disorder (ED/OCD) and schizophrenia. Females exhibited better functioning. Significant sex differences emerged in internalising symptoms (eg, anxiety/somatic/trauma, autism spectrum disorder (ASD)), externalising symptoms (eg, attention deficit hyperactivity disorder (ADHD)), overall psychopathology (eg, ADHD, personality disorder/conduct disorder/substance use disorder) and functioning (eg, ED/OCD, schizophrenia spectrum disorder). CONCLUSIONS:Sex-related differences in symptom severity, diagnosis and functioning persist across the CAMHS-AMHS transition, with males generally more impaired and females showing better adaptive outcomes. CLINICAL IMPLICATIONS/CONCLUSIONS:Identifying sex-specific trajectories can enhance personalised transitional care, reduce misdiagnosis and guide targeted interventions-especially for under-recognised presentations such as ADHD/ASD in females and ED in males. TRIAL REGISTRATION NUMBER/BACKGROUND:ISRCTN83240263.

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.

OBJECTIVE/UNASSIGNED:Gender-diverse individuals often face a burden of poor mental health. This study examined whether gender-diverse experiences were associated with higher levels of loneliness in adolescents, over and above depression and anxiety, and how family environmental factors, including maladaptive parenting, being bullied by a sibling at home (victimization), and bullying a sibling at home (perpetration), moderate the associations between gender-diverse and loneliness experiences among 4,424 adolescents in a population-based cohort. METHOD/UNASSIGNED:This cross-sectional study was embedded in Generation R, a multiethnic population-based cohort from fetal life onward. Adolescents with information on self-reported or parent-reported gender diversity and loneliness at ages 13 to 15 years were included. RESULTS/UNASSIGNED:s > .10). CONCLUSION/UNASSIGNED:Gender diversity is associated with higher levels of loneliness in adolescents. Being a target of bullying modified the association of gender diversity with loneliness experiences, suggesting that gender-diverse adolescents who are bullied by siblings experience particularly higher levels of loneliness.

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.

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/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.