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Prenatal and early-life determinants of neurodevelopment: A decade of discoveries and new directions in ABCD

Menu, Iris; Cachia, Arnaud; Thomason, Moriah E
Decades of research on the developmental origins of health and disease highlight how prenatal and perinatal conditions are associated with long-term neurocognitive development. Exposures such as maternal stress, substance use, metabolic disorders, obstetric complications, low birthweight, and preterm birth have been linked to differences in brain, cognition, and mental health. Yet, most prior studies have been limited by small sample sizes, narrow exposure measures, or isolated outcomes. The Adolescent Brain Cognitive Development (ABCD) Study provides an unparalleled opportunity to overcome these limitations with nearly 12,000 children recruited at ages 9-10 across the United States, followed longitudinally with harmonized multimodal MRI, cognitive and behavioral testing, biospecimens, genetic data, and rich environmental measures in a diverse cohort. Retrospective caregiver reports provide key prenatal and perinatal information, which can be prospectively related to neurodevelopmental outcomes across adolescence. This review synthesizes findings from 111 ABCD-based studies published from 2017 to 2026. Results implicate maternal health conditions, substance use, birth outcomes, and cumulative adversity as being associated with variation in brain, cognitive, and behavioral development. Leveraging its size and diversity, ABCD has fostered advanced analytic approaches, such as multimodal integration of imaging and behavioral data, and longitudinal tracking of developmental trajectories, rarely possible elsewhere. While methodological challenges remain, including retrospective reporting and imaging site variability, ABCD offers unique opportunities to clarify pathways of vulnerability and resilience within an observational framework. Insights from this work can inform public health strategies and guide policies to reduce prenatal risks and strengthening early-life environments to optimize developmental outcomes.
PMCID:13234727
PMID: 42202718
ISSN: 1878-9307
CID: 6071204

'Until You Get the Diagnosis You're Forever in Limbo'-Parents' Experiences of Waiting for an Attention-Deficit/Hyperactivity Disorder Assessment With Child and Adolescent Mental Health Services

Hedstrom, Ellen; Kostyrka-Allchorne, Katarzyna; Ballard, Claire; James, Naomi; Wright, Hannah; Daley, David; Glazebrook, Cris; Kreppner, Jana; Cattel, Claire; Gordon, Douglas; Gordon, Natalie; Tuttlebee, Tessa; Sonuga-Barke, Edmund
BACKGROUND:Parents in the United Kingdom seeking an assessment for attention-deficit/hyperactivity disorder (ADHD) for their child experience a significant wait before receiving an appointment with Child and Adolescent Mental Health Services (CAMHS), yet little has been written on how parents experience this period. Through qualitative interviews, we sought to understand how the period of waiting from being accepted onto a service waitlist and receiving a diagnostic assessment impacts parents and their children. METHOD:The study was nested within a large randomised controlled trial. We conducted semi-structured interviews with 41 parents of children aged 5-11 years. 30% of parents had waited between 18 and 24 months on a CAMHS waitlist, with 10% waiting more than 2 years. Reflexive thematic analysis was used to analyse data. RESULTS:At the point of the interview, around 50% of children were still waiting for an initial assessment. Six themes reflecting parents' uncertainty around the assessment process, lack of communication from services, the importance of receiving a diagnosis, difficulty accessing support and the negative impact of waiting on mental health and education, as well as recommendations to improve communication between services and families, emerged. CONCLUSION:Parents recognised the pressures on services to offer timely support; however, their well-being could be substantially improved by more clarity around wait times, as well as more effective signposting and support from services concerning the assessment process. This may help alleviate some of the stressors associated with their child's assessment journey, such as feeling responsible for their child's difficulties and the burden of supporting their educational needs. PATIENT AND PUBLIC CONTRIBUTION:This study was nested within the OPTIMA trial, where PPI panel members provided ongoing support in various aspects of the study, including advising on participant communication, study design and data analysis. All PPI members have lived experience of having a neurodivergent child. For this study, the PPI co-produced the interview schedule and took part in transcript analysis using a thematic framework approach. To acknowledge their contributions, members of the PPI panel are included as co-authors.
PMCID:12848897
PMID: 41603377
ISSN: 1369-7625
CID: 6071055

Fetal Cardiomyopathy in the Contemporary Era: A Multicenter Fetal Heart Society Research Collaborative Study

McBrien, Angela; Burande, Astha; Caluseriu, Oana; Conway, Jennifer; Peyvandi, Shabnam; Bolin, Elijah; Cavallé-Garrido, Tiscar; Chandra, Sue; Cnota, James; Creighton, Sara; Cuneo, Bettina F; Despres, Marlayna; Doan, Tam T; Doucet, J Scott; Freud, Lindsay R; Grenier, Michelle; Hogan, Whitnee; Kaplinski, Michelle; Kavanaugh-McHugh, Ann; Keller, Sam; Kwon, Elena N; Lad, Mrinal; Leslie, Meredith; Majeed, Amara; Mansukhani, Gitanjali; McIntosh, Amanda M; McVadon, Deani; Michelfelder, Erik; Miller, Michelle; Milligan, Caitlin; Montes Gil, Adriana; Moon-Grady, Anita J; Mulla, Neda; Patel, Sheetal R; Pruitt, Cathleen; Qasim, Amna; Rajagopal, Hari G; Ro, Sanghee; Schidlow, David; Scheider, Kristin; Srinivasan, Ranjini; Sutton, Jennifer; Taylor, Carolyn; Trivedi, Mahima K; Mital, Seema; Lipshultz, Steven E; Hornberger, Lisa K
BACKGROUND/UNASSIGNED:Fetal cardiomyopathy is a rare condition, often with an unknown cause and associated with high perinatal mortality. Recent years have seen improvement in fetal cardiac screening, genetic testing, and management. We sought to investigate genetic associations and clinical outcomes of fetal cardiomyopathy in the contemporary era. METHODS/UNASSIGNED:A single-arm (descriptive) retrospective cohort study of fetal cardiomyopathy cases diagnosed from January 2017 to December 2021 at 26 North American centers in the Fetal Heart Society Research Collaborative was undertaken. Cases attributable to maternal diabetes, extra-cardiac conditions, structural heart disease, or arrhythmias were excluded. Genetic testing results, extra-cardiac structural anomalies, and outcomes were collected. Logistic regression was performed to determine prenatal risk factors for death or cardiac transplantation by 1-year of age. Descriptive competing-risk analyses (cumulative incidence functions) and Kaplan-Meier survival estimates were used to describe outcomes. Multivariable logistic regression with 5 prespecified covariates was performed to identify prenatal factors associated with death or cardiac transplantation by 1-year of age. RESULTS/UNASSIGNED:≤0.001) were significantly associated with death or transplant by 1-year of age. CONCLUSIONS/UNASSIGNED:Fetal cardiomyopathy outcomes have improved in the current era, although only half achieve 1-year cardiac transplant-free survival. Genetic testing identifies a cause in one-third of cases. Hydrops at the time of fetal cardiomyopathy diagnosis and a prenatal diagnosis of extra-cardiac structural anomalies remain important risk factors for mortality.
PMID: 42565234
ISSN: 1941-3297
CID: 6070869

Sleep health in black families: bedtime routines and sleep patterns among young children

Chung, Alicia; Stanton-Koko, Monica; Johnson, Willa; Seixas, Azizi; Chung, Debbie; Iruka, Iheoma U; Brotman, Laurie; Huang, Keng-Yen; Jean-Louis, Girardin
INTRODUCTION/UNASSIGNED:Young Black children experience poorer sleep health than children from other racial/ethnic groups. Tailored family-centered interventions are needed to improve sleep health among young Black children. Tailoring requires information about parent perceptions, practices and context. The purpose of this study was to (1) understand the contextual definition of sleep health for Black families; (2) bedtime routines and sleep practices among Black families; and (3) parent preferences that may inform intervention design. METHODS/UNASSIGNED:We engaged 30 Black parents of 3-8-year-old children with mild sleep problems (e.g., child takes >30 min to fall asleep at bedtime) in this study. Parents completed three ratings scales about sleep health practices and child bedtime behavior and a semi-structured interview. Statistical analysis included descriptive statistics and correlations. We used an implementation science rapid qualitative analysis approach to analyze qualitative data from the interviews. RESULTS/UNASSIGNED:The final sample identified as 52% African-American, 14% Jamaican, 10% Haitian, and 26% mixed multi-ethnic groups. Parent mean age was 41 years and child mean age were 5 years old. About 80% of responders were women. About one-third of the sample held a doctoral degree, and half the sample had a bachelor's or Master's degree. Parents answered 56% of sleep knowledge questions accurately (ranging from 32 to 100%) and reported an average of two sleep problems. Parents described healthy sleep as involving flexibility in sleep timing and bedtime routines. More than half of parents reported co-sleeping practices, with reasons ranging from a strategy to address night wakings, to a way to preserve bonding. Later child bedtime (after 9 pm) was associated with bedtime resistance, permissive parenting, and parent stress. Many parents reported that they had poor sleep quality and duration. DISCUSSION/UNASSIGNED:Findings elucidate a range of factors to consider in tailoring sleep health interventions for Black families of young children. These include the common practice of co-sleeping, parents' value for flexibility related to bedtime and bedtime routines, and parents' own challenges with getting enough and good quality sleep. Tailored family-centered interventions will benefit from considering these factors.
PMCID:13449300
PMID: 42569147
ISSN: 2813-2890
CID: 6070882

Infant and maternal mental health in primary care: A guide for pediatricians and residency training programs

De Oliveira, Roberta Guimaraes; George, Gabriella E; Key, Danielle; Tomopoulos, Suzy
Childhood mental health, emotional, and behavioral problems are common and have reached crisis proportions, yet they often go undetected and untreated despite being responsible for significant morbidity and mortality. Approximately 16% of children under 6 years of age have clinically significant mental health difficulties, which require attention in early life1 Early intervention in infant mental health can have a profound impact on a child's future development and well-being. While pediatric primary care is an ideal setting for early detection of mental, emotional, and behavioral symptoms and social determinants of health, until recently, mental health training for pediatric residents was limited to elective experiences that were not standardized nor mandatory. With the recent ACGME addition of a required mental health rotation in pediatric residency curricula, our service assembled a panel of experts in infant mental health to identify the most important curricular elements to include as part of the Pediatrics Mental Health rotation in our safety net hospital. In the Pediatric Mental Health rotation at our institution, one of the four pediatric mental health rotation weeks was dedicated to Infant/Preschool Mental Health (0-6 years old). This manuscript provides background information and resources that can be used by pediatricians, and which can assist in the process of designing curricula for pediatric residents.
PMID: 42557199
ISSN: 1538-3199
CID: 6070835

Large language model applications for real-time clinical mental health assessment: Current potential and future directions

Aafjes-van Doorn, Katie; Ty, Francine Cheng; Hua, Antonia Yuxin; An, Chunlin; Van Meter, Anna
Large language models (LLMs) have shown increasing promise in the mental health field. LLMs are especially well suited to play a role in the labor-intensive, costly process of clinical assessment, as they can interact with a patient or participant directly to conduct a mental health assessment. We conducted a preregistered scoping review to (a) describe the unique capabilities of LLMs for clinical assessment, (b) determine the current state of the field in applying LLMs to directly assess patient/participant mental health (including screening, diagnosis, and monitoring of symptoms), and (c) highlight future research to facilitate the application of LLMs. We included work published in both Chinese and English. Only 10 studies met criteria for direct LLM-based mental health assessment. The evidence base was recent and heterogeneous: Four studies focused primarily on diagnostic interviewing or classification, five on symptom or severity assessment, and one on task-based multimodal depression assessment. Studies varied across text, voice, and multimodal formats, and depression was the dominant target. Across studies, stronger performance tended to be reported in tools that used structured interviewing logic, domain-specific adaptation, and clinically anchored reference standards. However, the evidence base remains small, with many studies employing limited validation procedures, and heavily weighted toward early-stage or nonjournal publications. The limited pace of academic validation means that, at present, LLMs are best understood as emerging assessment-support tools rather than replacements for clinical evaluation. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
PMID: 42545345
ISSN: 2769-755x
CID: 6070794

Neonatal Medical Male Circumcision and Child Autism Diagnosis

McGrath, Monica; Li, Xiuhong; Jacobson, Lisa P; Leventhal, Bennett; Aschner, Judy L; Baker, Brennan; Garcia, Karla Cardoso; Dickerson, Aisha S; Elliott, Amy J; Ganiban, Jody; Goodrich, Amanda; Horton, Daniel B; Jarnecke, Melinda; Keim, Sarah; Lee, Brian K; Lynch, Courtney D; Klebanoff, Mark; Mutaru, Abdul-Manaf; Nguyen, Ruby H N; Schmidt, Rebecca J; Shin, Hyeong-Moo; Shuffrey, Lauren C; Slaughter, Jonathan L; Stroustrup, Annemarie; Zhu, Zhaozhong; Tobian, Aaron A R; Grabowski, M Kate; ,
IMPORTANCE/UNASSIGNED:Public concern and speculation have emerged around a possible link between neonatal male circumcision (NMC) and autism spectrum disorder (ASD). Evidence is limited and inconsistent. OBJECTIVE/UNASSIGNED:To examine associations between NMC and child ASD and autism-related traits and behaviors. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This prospective cohort study was conducted among cohort sites participating in the Environmental Influences on Child Health Outcomes (ECHO) Cohort between February 2003 and September 2025. Statistical analyses were conducted from November 2025 to February 2026. The analysis included male, singleton children with data on NMC status and child ASD. EXPOSURE/UNASSIGNED:NMC status within 28 days of birth at a medical facility. MAIN OUTCOMES AND MEASURES/UNASSIGNED:ASD diagnosis was based on parent report of diagnosis by a medical professional or documentation of criterion standard clinical assessments. Social Responsiveness Scale (SRS-2) T-scores assessed the presence and distribution of autism traits, and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) Autism Spectrum Problems subscale T-scores from the Child Behavior Checklist (CBCL) 1.5/5 assessed the occurrence of child autism-related behaviors. RESULTS/UNASSIGNED:The sample included 2771 male children from 14 ECHO sites, of whom 1840 (66%) were circumcised before hospital discharge, and 192 (7%) had an autism diagnosis. Among 1840 circumcised males, 108 (6%) had autism, compared with 84 of 931 uncircumcised males (9%). Mean (SD) age at autism diagnosis was 3.8 (2.2) years. Among circumcised males, 31 (4%) were administered acetaminophen during the procedure, and 128 (7%) within the 30 days after birth. After adjusting for confounders, there was no association between NMC and ASD diagnosis (odds ratio [OR], 0.83; 95% CI, 0.59-1.17). After stratification by region, preterm birth, and neonatal intensive care unit admission, an inverse or no association was observed between NMC and ASD diagnosis. Adjusted analyses showed no associations between NMC and SRS-2 continuous (β = -0.62; 95% CI, -1.46 to 0.22) or binary (OR, 0.75; 95% CI, 0.48-1.15) T-scores. Similarly, no associations were observed between NMC and CBCL 1.5/5 continuous (β = 0.01; 95% CI, -0.54 to 0.56) or binary (OR, 1.30; 95% CI, 0.75-2.26) T-scores. Overall, inverse or no associations were observed across all strata for SRS-2 and CBCL 1.5/5 outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cohort study yielded no evidence that NMC was associated with ASD risk, whether assessed by parent report of medical professional diagnosis or validated instruments measuring autism-related traits and behavior. These findings may provide reassurance for families who are considering or have elected NMC for their child.
PMCID:13434970
PMID: 42545713
ISSN: 2168-6211
CID: 6070797

A longitudinal resource for mapping interindividual variation in the aging connectome

MacKay-Brandt, Anna; Gazes, Yunglin; Garcia-Barnett, Daniel; Grebe, Lauren A; Ripley, Olivia; Gan, Kai Xuan; Trautman, Kristin D; Kramer, Melissa; Breland, Melissa M; Tobe, Russell; Franco, Alexandre R; Gabbay, Vilma; Milham, Michael; Colcombe, Stan J
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.
PMCID:13424306
PMID: 42532989
ISSN: 2052-4463
CID: 6070468

Loneliness and Bullying by Siblings in Gender-Diverse Adolescents: Results From the Population-Based Generation R Study

Xerxa, Yllza; Ghassabian, Akhgar; Hillegers, Manon H J; Agulleiro, Luis Martinez; Jansen, Pauline W; Busa, Samantha; Castellanos, Francisco Xavier; White, Tonya
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.
PMCID:13420606
PMID: 42534685
ISSN: 2949-7329
CID: 6070474

The manifestation of trauma in infants and toddlers: Understanding early health impacts and the importance of trauma informed care in pediatrics

George, Gabriella E; Riley, Kristen; Shernoff, Elisa; Garcia, Kathryn; Key, Danielle; Schufreider, Charles
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.
PMID: 42538178
ISSN: 1538-3199
CID: 6070491