Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11432
Characterizing the spectrum of irritability in preadolescence: Dimensional and pragmatic applications
OBJECTIVES/OBJECTIVE:Characterize the dimensional spectrum of preadolescent (PA) irritability, a robust transdiagnostic vulnerability marker, using the youth version of the Multidimensional Assessment Profiles Temper Loss (MAPS-TL-Youth) scale including common and with developmentally specific items. Based on this, derive and validate a clinically optimized irritability screener to flag psychopathology risk in preadolescents. METHODS:The normal:abnormal irritability spectrum was modeled using MAPS-TL-Youth data from the Multidimensional Assessment of Preschoolers Study (MAPS) Study PA wave (n = 340) via item response theory. Both cross-cutting core items from the MAPS scales and developmentally specific items were used to generate this dimension. Stepwise logistic regression was then used to optimize MAPS-TL-Youth irritability items in relation to Kiddie Schedule of Affective Disorders and Schizophrenia impairment to generate a clinically optimized irritability screener. Receiver operator characteristic analysis identified the irritability threshold for the screener. For the first time, youth self-report of their own irritability on the MAPS-TL was also modeled via the MAPS-TL-Youth-Self-Report (MAPS-TL-Youth-SR). RESULTS:Irritability was unidimensional and ranged from mild and common to severe and rare behaviors. Developmentally specific items allowed detection of more severe irritability. Items for the screener were identified in relation to concurrent impairment. These included low frustration tolerance and pathognomonic severe behaviors. The clinically optimized screener demonstrated very good sensitively (87%) and specificity (81%) in regard to concurrent irritability-related DSM disorders. Modeling of the MAPS-TL-Youth-SR yielded similar results. CONCLUSION/CONCLUSIONS:Characterizing the normal: abnormal spectrum of irritability in preadolescence advances application of Research Domain Criteria methods to this developmental period. This foundational work yielded two developmentally specified tools for irritability characterization in preadolescence: a nuanced dimensional scale to precisely characterize the full normal-abnormal irritability spectrum, and a pragmatic, clinically optimized screener suitable for real world use. Future application in mechanistic and clinical studies will be important for establishing validity and incremental utility.
PMCID:10654812
PMID: 37800620
ISSN: 1557-0657
CID: 5756392
Interferon ɛ restricts Zika virus infection in the female reproductive tract
Interferon ɛ (IFNɛ) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections. Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNɛ contributes to protection against ZIKV infection in vivo is unknown. In this study, we show that IFNɛ plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNɛ was expressed not only by epithelial cells in the FRT but also by immune and stromal cells at baseline or after exposure to viruses or specific Toll-like receptor (TLR) agonists. IFNɛ-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal but not subcutaneous ZIKV infection. IFNɛ deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNɛ protected Ifnɛ-/-
PMID: 37954158
ISSN: 2752-6542
CID: 5976802
Maternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease
Down syndrome (DS) is a genetic disorder caused by triplication of human chromosome 21. In addition to intellectual disability, DS is defined by a premature aging phenotype and Alzheimer's disease (AD) neuropathology, including septohippocampal circuit vulnerability and degeneration of basal forebrain cholinergic neurons (BFCNs). The Ts65Dn mouse model recapitulates key aspects of DS/AD pathology, namely age-associated atrophy of BFCNs and cognitive decline in septohippocampal-dependent behavioral tasks. We investigated whether maternal choline supplementation (MCS), a well-tolerated treatment modality, protects vulnerable BFCNs from age- and genotype-associated degeneration in trisomic offspring. We also examined the effect of trisomy, and MCS, on GABAergic basal forebrain parvalbumin neurons (BFPNs), an unexplored neuronal population in this DS model. Unbiased stereological analyses of choline acetyltransferase (ChAT)-immunoreactive BFCNs and parvalbumin-immunoreactive BFPNs were conducted using confocal z-stacks of the medial septal nucleus and the vertical limb of the diagonal band (MSN/VDB) in Ts65Dn mice and disomic (2N) littermates at 3-4 and 10-12 months of age. MCS trisomic offspring displayed significant increases in ChAT-immunoreactive neuron number and density compared to unsupplemented counterparts, as well as increases in the area of the MSN/VDB occupied by ChAT-immunoreactive neuropil. MCS also rescued BFPN number and density in Ts65Dn offspring, a novel rescue of a non-cholinergic cell population. Furthermore, MCS prevented age-associated loss of BFCNs and MSN/VDB regional area in 2N offspring, indicating genotype-independent neuroprotective benefits. These findings demonstrate MCS provides neuroprotection of vulnerable BFCNs and non-cholinergic septohippocampal BFPNs, indicating this modality has translational value as an early life therapy for DS, as well as extending benefits to the aging population at large.
PMID: 37890559
ISSN: 1095-953x
CID: 5608002
The Provision and Utilization of Telehealth within Academic Mental Health Clinics in North America during the COVID-19 Pandemic
OBJECTIVE/UNASSIGNED:To document the experience of 14 academic child and adolescent psychiatry programs in transitioning to and managing telehealth services during the COVID-19 pandemic. The goal was to understand how programs adopted and sustained telehealth during the pandemic. Telehealth was defined as services delivered via videoconferencing and telephony. METHOD/UNASSIGNED:In this descriptive study, faculty from 14 programs completed online surveys about the use of both telehealth and in-person services from February 2020 to June 2021. Survey questions addressed telehealth practices (e.g., policies, support resources), monthly service utilization, telehealth modality (videoconferencing vs. telephony), and missed appointments. RESULTS/UNASSIGNED:Programs varied in the proportion of appointments delivered by telehealth prior to the pandemic (February 2020; 0-27%). By May 2020 all programs were providing a majority of visits via telehealth (64-100%). In June 2021, all programs continued to provide services via telehealth (41% to 100%) and reported that they would continue to do so moving forward. Programs addressed many challenges to telehealth provision during the study period, including adding interpreter services, technological support for providers and patients, and formalizing safety and training requirements. CONCLUSION/UNASSIGNED:Academic child and adolescent psychiatry programs provided outpatient services primarily via telehealth throughout the COVID-19 pandemic and reported that they planned to continue utilizing telehealth in combination with in-person services moving forward. Academic programs should therefore address logistical, technological, and financial barriers to the sustained use of telehealth.
PMCID:11364370
PMID: 39220686
ISSN: 2949-7329
CID: 5687602
Developmentally specified characterization of the irritability spectrum at early school age: Implications for pragmatic mental health screening
OBJECTIVES/OBJECTIVE:Developmentally specified measures that identify clinically salient irritability are needed for early school-age youth to meaningfully capture this transdiagnostic risk factor for psychopathology. Thus, the current study modeled the normal:abnormal irritability spectrum and generated a clinically optimized screening tool for this population. METHODS:The irritability spectrum was modeled via the youth version of the Multidimensional Assessment Profile Scales-Temper Loss Scale (MAPS-TL-Youth) in children (n = 474; 6.0-8.9 years) using item response theory (IRT). Both cross-cutting core irritability items from the early childhood version and new developmentally specific items were included. Items uniquely associated with impairment were identified and used to derive a brief, clinically optimized irritability screener. Longitudinal data were then utilized to test the predictive utility of this clinically optimized screener in preadolescence (n = 348; 8.0-12.9 years). RESULTS:Most children exhibit irritability regularly, but daily occurrence was rare. Of the top 10 most severe items from the IRT analyses, 9 were from the developmentally specific items added for the MAPS-TL Youth version. Two items associated with concurrent impairment were identified for the clinically optimized irritability screener ("Become frustrated easily" and "Act irritable"). The MAPS-TL-Youth clinically optimized screener demonstrated good sensitivity (69%) and specificity (84%) in relation to concurrent DSM 5 irritability-related diagnoses. Youth with elevated scores on the screener at early school age (ESA) had more than 7x greater odds of irritability-related psychopathology at pre-adolescence. CONCLUSIONS:The MAPS-TL-Youth characterized the developmental spectrum of irritability at ESA and a clinically optimized screener showed promise at predicting psychopathology risk. Rigorous testing of clinical applications is a critical next step.
PMCID:10654842
PMID: 37712753
ISSN: 1557-0657
CID: 5593622
Trauma-informed care in school-based health centers: A mixed methods study of behavioral health screening and services
An explanatory, parallel mixed method design was used to examine trauma screening and behavioral health service rates in urban school-based health centers (SBHCs) and SBHC personnel's experiences providing culturally responsive, trauma-informed care. Logistic regressions were performed with electronic medical records from N = 4,794 patients ages 12-22 receiving care in a SBHC using trauma screening rates and service use as dependent variables. Quantitative analyses were supplemented with semistructured interviews with medical providers and behavioral health clinicians (N = 9) from eight SBHCs. The overall trauma screening rate across the SBHCs was 69.2%. Screening rates were higher for older and Spanish-speaking youth. The rate of behavioral health use was 32.9%, with higher rates among students screened for trauma at a prior medical visit, recent immigrant, and female youth. This suggests that trauma screening is feasible and facilitates access. Additionally, English-speaking youth were more likely to use behavioral health services than Spanish-speakers. Qualitative analyses suggested a strong sense of mission, collaboration, and beliefs that trauma screening facilitated access to care all facilitated trauma-focused screening. Barriers included staffing shortages and language translation challenges. Analysis also highlighted the importance of culturally responsive practices (e.g., interpreters, culture-specific assessment tools, knowledge of population needs). Mixed methods integrative analysis highlighted the ways in which barriers and facilitators aligned with the overall rates of access to screening and behavioral health care, and factors that helped the SBHCs tailor care to diverse youth. Limitations and implications for practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
PMID: 38127527
ISSN: 2578-4226
CID: 5742932
Neuroscience: Building better cognition through smell [Comment]
Developmental neural activity organizes sensory system development. New evidence in mice suggests postnatal olfactory bulb activity also modulates development of the structure and function of hippocampal-cortical circuits. Reducing cell-specific olfactory bulb output during an infant sensitive period impairs later-life cognition.
PMID: 37875078
ISSN: 1879-0445
CID: 5708342
Interictal spikes in Alzheimer's disease: Preclinical evidence for dominance of the dentate gyrus and cholinergic control by the medial septum
Interictal spikes (IIS) are a common type of abnormal electrical activity in Alzheimer's disease (AD) and preclinical models. The brain regions where IIS are largest are not known but are important because such data would suggest sites that contribute to IIS generation. Because hippocampus and cortex exhibit altered excitability in AD models, we asked which areas dominate the activity during IIS along the cortical-CA1-dentate gyrus (DG) dorso-ventral axis. Because medial septal (MS) cholinergic neurons are overactive when IIS typically occur, we also tested the novel hypothesis that silencing the MS cholinergic neurons selectively would reduce IIS. We used mice that simulate aspects of AD: Tg2576 mice, presenilin 2 (PS2) knockout mice and Ts65Dn mice. To selectively silence MS cholinergic neurons, Tg2576 mice were bred with choline-acetyltransferase (ChAT)-Cre mice and offspring were injected in the MS with AAV encoding inhibitory designer receptors exclusively activated by designer drugs (DREADDs). We recorded local field potentials along the cortical-CA1-DG axis using silicon probes during wakefulness, slow-wave sleep (SWS) and rapid eye movement (REM) sleep. We detected IIS in all transgenic or knockout mice but not age-matched controls. IIS were detectable throughout the cortical-CA1-DG axis and occurred primarily during REM sleep. In all 3 mouse lines, IIS amplitudes were significantly greater in the DG granule cell layer vs. CA1 pyramidal layer or overlying cortex. Current source density analysis showed robust and early current sources in the DG, and additional sources in CA1 and the cortex also. Selective chemogenetic silencing of MS cholinergic neurons significantly reduced IIS rate during REM sleep without affecting the overall duration, number of REM bouts, latency to REM sleep, or theta power during REM. Notably, two control interventions showed no effects. Consistent maximal amplitude and strong current sources of IIS in the DG suggest that the DG is remarkably active during IIS. In addition, selectively reducing MS cholinergic tone, at times when MS is hyperactive, could be a new strategy to reduce IIS in AD.
PMID: 37714307
ISSN: 1095-953x
CID: 5593282
Reduced Cholecystokinin-Expressing Interneuron Input Contributes to Disinhibition of the Hippocampal CA2 Region in a Mouse Model of Temporal Lobe Epilepsy
A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is extensive cell loss in the hippocampal CA1 and CA3 subfields, with a relative sparing of dentate gyrus granule cells and CA2 pyramidal neurons (PNs). A role for CA2 in seizure generation was suggested based on findings of a reduction in CA2 synaptic inhibition (Williamson and Spencer, 1994) and the presence of interictal-like spike activity in CA2 in resected hippocampal tissue from TLE patients (Wittner et al., 2009). We recently found that in the pilocarpine-induced status epilepticus (PILO-SE) mouse model of TLE there was an increase in CA2 intrinsic excitability associated with a loss of CA2 synaptic inhibition. Furthermore, chemogenetic silencing of CA2 significantly reduced seizure frequency, consistent with a role of CA2 in promoting seizure generation and/or propagation (Whitebirch et al., 2022). In the present study, we explored the cellular basis of this inhibitory deficit using immunohistochemical and electrophysiological approaches in PILO-SE male and female mice. We report a widespread decrease in the density of pro-cholecystokinin-immunopositive (CCK+) interneurons and a functional impairment of CCK+ interneuron-mediated inhibition of CA2 PNs. We also found a disruption in the perisomatic perineuronal net in the CA2 stratum pyramidale. Such pathologic alterations may contribute to an enhanced excitation of CA2 PNs and CA2-dependent seizure activity in the PILO-SE mouse model.SIGNIFICANCE STATEMENT Impaired synaptic inhibition in hippocampal circuits has been identified as a key feature that contributes to the emergence and propagation of seizure activity in human patients and animal models of temporal lobe epilepsy (TLE). Among the hippocampal subfields, the CA2 region is particularly resilient to seizure-associated neurodegeneration and has been suggested to play a key role in seizure activity in TLE. Here we report that perisomatic inhibition of CA2 pyramidal neurons mediated by cholecystokinin-expressing interneurons is selectively reduced in acute hippocampal slices from epileptic mice. Parvalbumin-expressing interneurons, in contrast, appear relatively conserved in epileptic mice. These findings advance our understanding of the cellular mechanisms underlying inhibitory disruption in hippocampal circuits in a mouse model of spontaneous recurring seizures.
PMCID:10573827
PMID: 37643861
ISSN: 1529-2401
CID: 5605122
Journal of the American Academy of Child and Adolescent Psychiatry. 2023:62(Supplement 10).DOI: 10.1016/j.jaac.2023.07.143
Racism as Trauma: The Impact of Intergenearational Trauma on Black Youth
ORIGINAL:0017048
ISSN: 0890-8567
CID: 5572032
