Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11432
Research Agenda in Childhood Impairing Emotional Outbursts: A Report of the AACAP Presidential Taskforce on Emotional Dysregulation
OBJECTIVE/UNASSIGNED: The research agenda is presented here. METHOD/UNASSIGNED:The Taskforce specifically focused on aggressive behaviors and emotions associated with outbursts. The development of a research agenda took place over 2 years of examination of the current needs in the literature, with contributions from experts in the field. This work dovetailed with the efforts from the Congress on Pediatric Irritability and Dysregulation, which had been meeting since 2015 to advance research into the measurement, pathophysiology, and treatment of emotion regulation problems in youth. We concentrated on the central questions concerning the measurement of outbursts, key questions linking outbursts to other psychopathologies, and how behavior in outbursts is separable from typical behavior. RESULTS/UNASSIGNED:A description of the qualitative data gathering process is provided here, along with the following: recommendations in the research areas of measurement; pathophysiology; delineating outbursts from other psychopathologies; exploring the cultural, social, and interpersonal aspects of outbursts; understanding the prevention and treatment of outbursts; and exploring how outbursts manifest and are treated based on setting. Specific examples of research opportunities and future directions are provided. CONCLUSION/UNASSIGNED:A call is made to funding agencies to examine the spaces within their strategic plans that will allow for engagement in critical efforts to improve the lives of children and adolescents with severe emotional outbursts-some of the most impaired individuals presenting for care in child and adolescent psychiatry.
PMCID:11914913
PMID: 40109494
ISSN: 2949-7329
CID: 5813502
Journal of the American Academy of Child and Adolescent Psychiatry. 2025:64(3):329-345.DOI: 10.1016/j.jaac.2024.10.015
Umbrella Review and Meta-Analysis: The Efficacy of Nonpharmacological Interventions for Sleep Disturbances in Children and Adolescents
OBJECTIVE:We conducted an umbrella review of systematic reviews (SRs), with or without meta-analysis (MA), of randomized controlled trials (RCTs) assessing nonpharmacological sleep interventions for children and adolescents across various clinical populations. METHOD/METHODS:We searched multiple electronic databases up to January 24, 2024. Meta-analyzable data from RCTs in the retrieved SRs/MAs were pooled using Metaumbrella. Primary outcomes were subjective/objective child sleep parameters. Additional outcomes included child health/functioning and parental sleep/health. The quality of the MAs/SRs was assessed with Assessment of Multiple Systematic Reviews (AMSTAR-2), and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS:We included 93 SRs/MAs covering 393 RCTs, with 25 (17%, 39%, and 30%: high, moderate, and low quality) providing data for quantitative synthesis. Behavioral interventions, usually multicomponent including parent training, psychoeducation, and/or specific sleep therapy/strategies, showed beneficial effects on night waking, sleep duration, overall sleep disturbance, mood/depression, and maternal sleep quality (standardized mean difference [SMD] = 0.10-0.80) in participants with sleep problems without a formal sleep disorder diagnosis. For those with a formal diagnosis (mainly insomnia), benefits were found for night waking, sleep efficiency (subjective/actigraphically measured), and sleep onset latency (mean SMD = 0.49-0.97). Those with attention-deficit/hyperactivity disorder (ADHD) improved in bedtime resistance, night waking, parasomnias, sleep anxiety, ADHD symptoms, sleep disturbance, and quality of life (mean SMD = 0.18-0.49). For those with autism, sleep disturbance improved (mean SMD = 0.70). However, all findings were of low to very low certainty of evidence. CONCLUSION/CONCLUSIONS:Among nonpharmacological interventions for sleep difficulties in youth, only behavioral interventions are supported by meta-analytic evidence, yet with small-to-moderate effect sizes and limited certainty of evidence. STUDY PREREGISTRATION INFORMATION/UNASSIGNED:The efficacy and tolerability of nonpharmacological interventions for sleep problems in children and adolescents: protocol for an umbrella review of systematic reviews and meta-analyses of randomised controlled trials. https://osf.io; j9qna/.
PMID: 39608635
ISSN: 1527-5418
CID: 5781702
Genomics yields biological and phenotypic insights into bipolar disorder
Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
PMID: 39843750
ISSN: 1476-4687
CID: 5778012
Early White Matter Microstructure Alterations in Infants with Down Syndrome
IMPORTANCE/UNASSIGNED:Down syndrome, resulting from trisomy 21, is the most prevalent chromosomal disorder and a leading cause of intellectual disability. Despite its significant impact on brain development, research on the white matter microstructure in infants with Down syndrome remains limited. OBJECTIVE/UNASSIGNED:To investigate early white matter microstructure in infants with Down syndrome using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). DESIGN/UNASSIGNED:Infants were recruited and scanned between March 2019 and May 2024 as participants in prospective studies conducted by the Infant Brain Imaging Study (IBIS) Network. Data were analyzed in October 2024. SETTING/UNASSIGNED:Data collection occurred at five research centers in Minnesota, Missouri, North Carolina, Pennsylvania, and Washington. PARTICIPANTS/UNASSIGNED:Down syndrome and control infants were scanned at 6 months of age. Control infants had no Down syndrome diagnosis and either had a typically developing older sibling or, if they had an older sibling with autism, were confirmed not to meet clinical best estimate criteria for an autism diagnosis. EXPOSURE/UNASSIGNED:Diagnosis of Down syndrome. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The outcome of interest was white matter microstructure quantified using DTI and NODDI measures. RESULTS/UNASSIGNED:A total of 49 Down syndrome (28 [57.14%] female) and 37 control (18 [48.65%] female) infants were included. Infants with Down syndrome showed significant reductions in fractional anisotropy and neurite density index across multiple association tracts, particularly in the inferior fronto-occipital fasciculus and superior longitudinal fasciculus II, consistent with reduced structural integrity and neurite density. These tracts also demonstrated increased radial diffusivity, suggesting delayed myelination. The inferior fronto-occipital fasciculus and uncinate fasciculus exhibited increased neurite dispersion and fanning in Down syndrome infants, reflected by elevated orientation dispersion index. Notably, the optic tracts in Down syndrome infants exhibited a distinct pattern of elevated fractional anisotropy and axial diffusivity, and lower radial diffusivity and orientation dispersion index, suggesting an early maturation of these pathways. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This first characterization of white matter microstructure in Down syndrome infants reveals widespread white matter developmental delays. These findings provide new insights into the early neurodevelopment of Down syndrome and may inform early therapeutic interventions.
PMCID:11888504
PMID: 40061339
CID: 5820462
Intersect between brain mechanisms of conditioned threat, active avoidance, and reward
Active avoidance is a core behavior for human coping, and its excess is common across psychiatric diseases. The decision to actively avoid a threat is influenced by cost and reward. Yet, threat, avoidance, and reward have been studied in silos. We discuss behavioral and brain circuits of active avoidance and the interactions with fear and threat. In addition, we present a neural toggle switch model enabling fear-to-anxiety transition and approaching reward vs. avoiding harm decision. To fully comprehend how threat, active avoidance, and reward intersect, it is paramount to develop one shared experimental approach across phenomena and behaviors, which will ultimately allow us to better understand human behavior and pathology.
PMCID:11864974
PMID: 40011644
ISSN: 2731-9121
CID: 5801092
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
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
Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury in Mice
PMCID:11860106
PMID: 40006049
ISSN: 1424-8247
CID: 5800842
DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders
BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. It is likely that gene-disruptive BCL11B variants and missense variants affecting zinc-binding cysteine and histidine residues cause mild to moderate neurodevelopmental delay with increased propensity for behavioral and dental anomalies, allergies and asthma, and reduced type 2 innate lymphoid cells. Missense variants within C2H2-ZnF DNA-contacting α helices cause highly variable clinical presentations ranging from multisystem anomalies with demise in the first years of life to late-onset, hyperkinetic movement disorder with poor fine motor skills. Those not in direct DNA contact cause a milder phenotype through reduced, target-specific transcriptional activity. However, missense variants affecting C2H2-ZnFs, DNA binding, and "specificity residues" impair BCL11B transcriptional activity in a target-specific, dominant-negative manner along with aberrant regulation of alternative DNA targets, resulting in more severe and unpredictable clinical outcomes. Taken together, we suggest that the phenotypic severity and variability is largely dependent on the DNA-binding affinity and specificity of altered BCL11B proteins.
PMID: 39798569
ISSN: 1537-6605
CID: 5775812
Monosodium glutamate: A hidden risk factor for obesity?
Monosodium glutamate (MSG) has become one of the most widely used food additives in the global food supply. Although it has been classified for decades as a food ingredient that is generally recognized as safe, concerns about the health impacts of chronic MSG use, especially its potential effect on weight, are still ongoing. This comprehensive review summarizes the available human and animal evidence, highlighting potential mechanisms linking MSG use to weight gain or obesity, and discusses challenges and future research directions. Because of MSG intake worldwide as well as hidden MSG in food labeling, there is a pressing need for a mechanistic understanding of the health impacts of MSG use especially on weight. To generate robust scientific evidence and to clarify public concerns, rigorous mechanistic studies and randomized controlled clinical trials are warranted.
PMID: 39914377
ISSN: 1467-789x
CID: 5784272
