Faculty Bibliography
Searched for:
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11622
Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder
Obsessive-compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D1 and D2 type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index.
PMID: 40360802
ISSN: 1546-1718
CID: 5844232
Breaking the Cycle: Predicting Agitation Crises in Child and Adolescent Inpatient Psychiatry
This study examined biopsychosocial factors associated with the use of intramuscular (IM) agitation emergency medication in child and adolescent psychiatric inpatients. A retrospective review of 1,101 patients hospitalized between June 2018-November 2021 at an urban teaching hospital identified predictors of IM medication use through linear regression analysis. Among these patients, 196 received IM medication during their stay. Female sex was associated with a lower likelihood of receiving IM treatment, while factors such as prior involvement with child protective services, a history of violence, previous psychiatric hospitalizations, and use of multiple home psychiatric medications increased the likelihood. Agitation episodes pose risks to both patients and staff, underscoring the importance of early identification and intervention. Understanding these risk factors may guide proactive strategies to reduce the frequency and severity of agitation and limit reliance on emergency pharmacological interventions. Further research is needed to refine predictive models and explore non-pharmacological management approaches.
PMID: 40377832
ISSN: 1573-3327
CID: 5844742
Increased excitability of dentate gyrus mossy cells occurs early in life in the Tg2576 model of Alzheimer's disease
BACKGROUND:Hyperexcitability in Alzheimer's disease (AD) is proposed to emerge early and contribute to disease progression. The dentate gyrus (DG) and its primary cell type, granule cells (GCs) are implicated in hyperexcitability in AD. Hence, we hypothesized that mossy cells (MCs), important regulators of GC excitability, contribute to early hyperexcitability in AD. Indeed, MCs and GCs are linked to hyperexcitability in epilepsy. METHODS:Using the Tg2576 model of AD and WT mice (~ 1 month-old), we compared MCs and GCs electrophysiologically and morphologically, assessed the activity marker c-Fos, Aβ expression and a hippocampal- and MC-dependent memory task that is impaired at 3-4 months of age in Tg2576 mice. RESULTS:Tg2576 MCs had increased spontaneous excitatory events (sEPSP/Cs) and decreased spontaneous inhibitory currents (sIPSCs), increasing the excitation/inhibition ratio. Additionally, Tg2576 MC intrinsic excitability was enhanced. Consistent with in vitro results, Tg2576 MCs showed enhanced c-Fos protein expression. Tg2576 MCs had increased intracellular Aβ expression, suggesting a reason for increased excitability. GCs showed increased excitatory and inhibitory input without changes in intrinsic properties, consistent with effects of increased MC activity. In support, increased GC activity was normalized by an antagonist of MC input to GCs. Also in support, Tg2576 MC axons showed sprouting to the area of GC dendrites. These effects occurred before an impairment in the memory task, suggesting they are extremely early alterations. CONCLUSIONS:Alterations in Tg2576 MCs and GCs early in life suggest an early role for MCs in increased GC excitability. MCs may be a novel target to intervene in AD pathophysiology at early stages.
PMCID:12079945
PMID: 40375112
ISSN: 1758-9193
CID: 5844672
Understanding the development of a functional brain circuit: reward processing as an illustration
Aberrant reward processing is common in psychiatric disorders that begin during development. However, our understanding of the early reward system is limited, due to few studies assessing reward engagement across development. Moreover, the interpretation of these findings is based primarily on our understanding of the adult reward system. Here, we argue that approaches to early reward processing must be re-framed within the context of developmental transitions. This alternate perspective takes into account unique, age-specific brain network functions that promote adaptive behaviors as environmental demands change from infancy through childhood. We survey the literature on developing reward systems and ask the following critical questions: (1) how are rewarding stimuli defined for infants and children? (2) do adult-defined neural reward circuits also support early reward behavior? and (3) how can early circuit perturbation impact infant and adult circuit function? Altogether, we argue that this developmental niche-centered framework is needed for conceptually and theoretically approaching developmental research questions, including but also extending beyond the scope of reward. Finally, this framework can help us understand how disturbance in developmental processes may ultimately manifest as pathology.
PMCID:11832941
PMID: 39962048
ISSN: 2158-3188
CID: 5843022
Complications After Maternal Traumatic Brain Injury During Pregnancy: A Systematic Review
IMPORTANCE/UNASSIGNED:General trauma is the leading cause of nonobstetric maternal morbidity and mortality, affecting approximately 8% of all pregnancies. Pregnant women with traumatic brain injury (TBI) face high morbidity and mortality rates, requiring complex management due to physiological changes, teratogenic risks of treatments, and the need for fetal monitoring. OBJECTIVES/UNASSIGNED:To assess the consequences of TBI during pregnancy on maternal and fetal outcomes and to evaluate management strategies to inform clinical decision-making. EVIDENCE REVIEW/UNASSIGNED:A systematic literature search was conducted on January 12, 2024, in PubMed, Web of Science, and PsycInfo to identify articles published in English, German, or Spanish between January 1, 1990, and December 31, 2023, that included at least 1 pregnant individual with TBI. Peer-reviewed, human-based studies with original data on maternal and fetal outcomes were included. Reviews, meta-analyses, and nonhuman studies were excluded. Two independent reviewers screened abstracts and full-text articles. Study characteristics, pregnancy outcomes (maternal and fetal), management methods, and authors' conclusions were extracted. Risk of bias was assessed by 2 reviewers, with interrater agreement measured using Cohen κ. Disagreements were resolved through discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. FINDINGS/UNASSIGNED:This systematic review included 16 articles involving a total of 4112 individuals (mean maternal age, 26.9 years; range, 16-47 years) who experienced TBI during pregnancy (mean gestational age at injury, 24 weeks; range, 3-38 weeks). The articles comprised 10 case reports, 2 case series, and 4 cohort studies. Motor vehicle crashes were the most common cause of injury, reported in 12 articles. The average Glasgow Coma Scale score ranged from 3 to 15 across all individuals. Conservative management was reported in 7 case patients, whereas surgery was performed in 6 case patients. Maternal outcomes ranged from functional recovery to severe cognitive impairment, and fetal outcomes varied from stable to severe adverse outcomes, including stillbirth and death. Risk of bias assessment indicated moderate to good methodological validity overall, but most articles demonstrated poor quality of evidence. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this review, no definitive association between TBI during pregnancy and maternal or fetal outcomes was found owing to conflicting findings, poor to moderate study quality, and limited evidence. Although some articles suggested increased risks such as placental abruption and cesarean delivery, the findings remained inconclusive. The findings of this review underscore the need for high-quality research, standardized reporting, and rigorous methodology to improve data reliability. Future research should focus on developing consensus-driven, multidisciplinary management strategies to improve maternal and fetal outcomes.
PMCID:11833521
PMID: 39960671
ISSN: 2574-3805
CID: 5843002
Reporting and Representation of Race and Ethnicity in Clinical Trials of Pharmacotherapy for Mental Disorders: A Meta-Analysis
IMPORTANCE/UNASSIGNED:Representation of race and ethnicity in randomized clinical trials (RCTs) is critical for understanding treatment efficacy across populations with different racial and ethnic backgrounds. OBJECTIVE/UNASSIGNED:To examine race and ethnicity representation and reporting across RCTs of pharmacotherapies for mental disorders. DATA SOURCES/UNASSIGNED:PubMed (Medline), Embase (Ovid), APA PsycInfo, and Web of Science were searched until March 1, 2024, to retrieve network meta-analyses including RCTs of pharmacotherapies for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision mental disorders. STUDY SELECTION/UNASSIGNED:RCTs that recruited people of any age with a diagnosis of a mental disorder and that tested the efficacy of any pharmacologic intervention vs any control arm. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Random-effects logit-transformed proportion meta-analyses were used to estimate prevalence rates of race and ethnicity groups and their temporal trends across RCTs and to compare US RCT prevalence rates with US Census data. The Preferred Reporting Items for Overviews of Reviews was used to report our review. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Reporting of data and percentages of race and ethnicity. The year of publication, type of RCT, geographic location, age group, and sample size were also included. There were no deviations that occurred from the original protocol. RESULTS/UNASSIGNED:Data were obtained from 1683 RCTs (375 120 participants in total). Of these, 1363 (91.7% of participants) included participants aged 18 years or older; 680 RCTs (36.0% of participants) were from the US, 404 (17.1% of participants) were from Europe, and 293 (29.9% of participants) were from multiple geographic locations. Race and ethnicity were reported in 39.2% of RCTs; reporting was the highest in US-based RCTs (58.7%) and lowest in Central and South America (8.7%) and Asia and the Middle East (12.4%). Among participants, 2.7% (95% CI, 2.1%-3.5%) self-reported as Asian, 9.0% (95% CI, 8.1%-10.0%) as Black, 11.0% (95% CI, 9.1%-13.3%) as Hispanic among White, 80.2% (95% CI, 78.8%-81.5%) as White including Hispanic, and 5.8% (95% CI, 5.2%-6.4%) as other race or ethnicity, multiracial, or multiethnic. There was more frequent reporting of race and ethnicity in US RCTs (log odds increased by 0.066 each year) and less frequent reporting in non-US RCTs (log odds increased by 0.023 each year). Studies reporting race and ethnicity did not generally include larger sample sizes (mean sample size, 263.7 [95% CI, 15.0-860.3] participants) compared with those not reporting such data (mean sample size, 196.6 [95% CI, 12.0-601.3] participants), albeit not in all locations. In US RCTs, adults in the other or multiracial and multiethnic category were historically overrepresented, while adults in Asian, Black, Hispanic among White, and White including Hispanic categories were underrepresented; Asian, Black, and Hispanic among White children and adolescents are still currently underrepresented. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of this meta-analysis suggest that differences in reporting race and ethnicity across geographic locations and underrepresentation of certain racial and ethnic groups in US-based RCTs highlight the need for international guidelines to ensure equitable recruitment and reporting in clinical trials.
PMCID:12060014
PMID: 40332916
ISSN: 2168-6238
CID: 5839222
Autophagy Suppresses CCL2 to Preserve Appetite and Prevent Lethal Cachexia
UNLABELLED:restored food intake, suppressed cachexia and rescued lethality of autophagy-deficient mice. To test if appetite suppression by CCL2 was responsible for lethal cachexia we performed single nucleus RNA sequencing of the hypothalamus, the center of appetite control in the brain. Notably, we found that autophagy deficiency was specifically toxic to PMCH and HCRT neurons that produce orexigenic neuropeptides that promote food intake, which was rescued by deficiency in CCL2. Finally, the restoration of food intake via leptin deficiency prevented lethal cachexia in autophagy-deficient mice. Our findings demonstrate a novel mechanism where autophagy prevents induction of a cachexia factor, CCL2, which damages neurons that maintain appetite, the destruction of which may be central to degenerative wasting conditions. KEY POINTS OF PAPER/UNASSIGNED:1) Autophagy-deficient mice have reduced food intake, systemic inflammation, and cachexia2) CCL2, but not GDF15 or CXCL10, induces lethal cachexia caused by autophagy defect3) Autophagy-deficient mice have CCL2-dependent destruction of appetite-promoting neurons in the hypothalamus4) Leptin deficiency restores appetite and rescues lethal cachexia in autophagy-deficient mice5) Autophagy-deficient mice die from cachexia mediated by appetite loss6) Degenerative conditions due to impaired autophagy are caused by the inflammatory response to the damage7) Targeting CCL2 may be a viable approach to prevent degenerative wasting disorders.
PMCID:11888218
PMID: 40060612
ISSN: 2692-8205
CID: 5840732
Functional connectivity between the visual and salience networks and autistic social features at school-age
BACKGROUND:Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD. METHODS:Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was used to screen for associations between network-level functional connectivity and six behaviors of interest in a data-driven manner: social affect, restricted and repetitive behavior (RRB), generalized anxiety, inattention, motor coordination, and matrix reasoning. RESULTS:Functional connectivity between the visual and salience networks was significantly associated with social affect symptoms at school-age after accounting for all other behaviors. Results indicated that stronger connectivity was associated with higher social affect scores. No other behaviors were robustly associated with functional connectivity, though trends were observed between visual-salience connectivity and RRBs. CONCLUSIONS:Connectivity between the visual and salience networks may play an important role in social affect symptom variability among children with ASD and those with genetic liability for ASD. These findings align with and extend earlier reports in this sample of the central role of the visual system during infancy in ASD.
PMCID:12036130
PMID: 40295911
ISSN: 1866-1955
CID: 5838612
Improved Access to Behavioral Health Care for Patients in a Large New York City Behavioral Health Clinic by the Transition to Telemedicine
OBJECTIVE/UNASSIGNED:To examine the transition to telemental health within the behavioral health program of a large federally qualified health center, The Family Health Centers at NYU Langone, in the 3 months following the onset of the COVID-19 pandemic-specifically impacts on show rates and access to care. METHODS/UNASSIGNED:Demographic and clinical information for all scheduled visits was collected for two time periods: the telemental health period, March 16, 2020-July 16, 2020 (46,878 visits, 5,183 patients), and a comparison period, March 15, 2019-July 16, 2019 (47,335 visits, 5,190 patients). Data collected included modality, appointments scheduled/completed/cancelled/no-showed, age, gender, race, language, and diagnosis. Generalized estimating equations with a compound symmetry correlation structure and logit link were used for analysis. RESULTS/UNASSIGNED:= 0.01), which was eliminated by implementation of telemental health. CONCLUSIONS/UNASSIGNED:This study supports the use telemental health to increase access for all patients, including those from under-represented, lower socioeconomic status backgrounds.
PMCID:12040568
PMID: 40308563
ISSN: 2692-4366
CID: 5834012
Prenatal Superstorm Sandy stress and postnatal affectionless control as a conjoint risk for child psychopathology
The current study investigates the conjoint effect of prenatal Superstorm Sandy stress (SS) and postnatal parenting, as measured by affectionless control (AC), in determining the risk of early childhood psychopathology. The study included 154 children (45.5% males) longitudinally tracked from ages 2-5 years. Maternal AC was assessed using the Parental Bonding Instrument. The prevalence of child diagnostic outcomes (DSM-IV anxiety disorders, phobias, and disruptive behavior disorders) was ascertained by trained clinical interviewers using maternal responses to the Preschool Age Psychiatric Assessment. Children were stratified into four groups by SS and AC status to identify synergistic effects on psychopathology exceeding the risks expected in an additive model. Children exposed to both SS and AC had over 5-fold increased risk of any anxiety disorder, a 12-fold increased risk for disruptive behavior disorders, and a nearly 5-fold increased risk of any disorder relative to the reference group of children with neither exposure. The risks of anxiety, disruptive behavior, and any disorders were synergistically greater than the sum of independent effects of the two stressors, as evident in the synergy index. Evaluation of synergistically increased risks for childhood disorders will help to identify high-risk children, which in turn could inform design of multi-level interventions to mitigate child psychopathology.
PMCID:12043322
PMID: 40308331
ISSN: 1062-1024
CID: 5833992
