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Department/Unit:Child and Adolescent Psychiatry

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Gaze-Speech Coordination During Narration in Autism Spectrum Disorder and First-Degree Relatives

Xing, Jiayin; Lau, Joseph C Y; Nayar, Kritika; Landau, Emily; Kumareswaran, Mitra; Grabowecky, Marcia; Losh, Molly
PMCID:12839432
PMID: 41594827
ISSN: 2076-3425
CID: 6003272

Devaluation of response-produced safety signals reveals circuits for goal-directed versus habitual avoidance in dorsal striatum

Sears, Robert M; Andrade, Erika C; Samels, Shanna B; Laughlin, Lindsay C; Moloney, Danielle M; Wilson, Donald A; Alwood, Matthew R; Moscarello, Justin M; Cain, Christopher K
Active avoidance responses (ARs) are instrumental behaviors that prevent harm. Adaptive ARs may contribute to active coping, whereas maladaptive avoidance habits are implicated in anxiety and obsessive-compulsive disorders. The AR learning mechanism has remained elusive, as successful avoidance trials produce no obvious reinforcer. We used a novel outcome-devaluation procedure in rats to show that ARs are positively reinforced by response-produced feedback cues that develop into safety signals during training. Males were sensitive to feedback devaluation after moderate training, but not overtraining, consistent with a transition from goal-directed to habitual avoidance. Using chemogenetics and feedback devaluation, we also show that goal-directed vs. habitual ARs depend on dorsomedial vs. dorsolateral striatum, suggesting a significant overlap between the mechanisms of avoidance and rewarded instrumental behavior. Females were insensitive to feedbackdevaluation due to a remarkable context-dependence of counterconditioning. However, degrading the contingency between avoidance and feedback suggests that both sexes rely on safety signals to perform goal-directed ARs.
PMID: 41663373
ISSN: 2041-1723
CID: 6001832

A Mixed-Methods Pilot Study on Clinicians' Attitudes and Utilization of Complementary and Integrative Health Services for Patient Care at an Academic Medical Center

Millon, Emma M; Shang, Andrea; Bass, Benjamin; Pena, Giselle S; Alendy, Fariza; Zavotsky, Kathleen E; Delmore, Barbara; DeMarco, Kathleen A
PMID: 41467974
ISSN: 2768-3613
CID: 6001122

A double-blind, placebo-controlled, multi-crossover trial of treatment with a chemokine antagonist for knee osteoarthritis pain

Edwards, Robert R; Tarpey, Thaddeus; Ashburn, Michael; Baer, Caitlin; Campbell, Allison; Dworkin, Robert H; Gaspard, Gabrielle; Flynn, Martina; Hade, Erinn; Jain, Nitin; Judge, Heidi; Kamp, Cornelia; Li, Yi; Meropol, Sharon; Petkova, Eva; Philip, Annie; Przkora, Rene; Rathmell, James P; Robinson-Papp, Jessica; Samuels, Jonathan; Sehgal, Nalini; Sienty, Jackie; Stacey, Brett; Wallace, Mark; Wasan, Ajay D; Wise, Barton; Yu, Chang; Fava, Maurizio; Troxel, Andrea B
Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.
PMID: 41468282
ISSN: 1872-6623
CID: 6001132

The International Guideline for the Definition, Classification, Diagnosis and Management of Urticaria

Zuberbier, T; Abdul Hameed Ansari, Z; Abdul Latiff, A H; Abuzakouk, M M; Agcaoili-De Jesus, M S; Agondi, R C; Al-Ahmad, M; Alangari, A A; Alhameli, H; Alonso Bello, C D; Alshareef, S; Al-Tamemi, S; Altrichter, S; Al Wahshi, H; Aquilina, S; Araújo, M; Arnaout, R; Asero, R; Ballmer-Weber, B; Bangert, C; Bauer, A; Ben-Shoshan, M; Bernstein, J; Bindslev-Jensen, C; Bizjak, M; Boccon-Gibod, I; Bonnekoh, H; Bouillet, L; Brockow, K; Brzoza, Z; Bulatović Ćalasan, M; Bulkhi, A; Buttgereit, T; Bygum, A; Caballero, T; Calderon, O; Campos, R; Cancian, M; Carne, E; Castor, M A; Cerecedo, I; Çetinarslan, T; Cherrez-Ojeda, I; Chkhikvadze, N; Chong-Neto, H J; Choo, K; Christoff, G; Chu, C-Y; Ciupka, K; Conlon, N; Costa, C; Craig, T; Criado, P; Danilycheva, I; Darlenski, R; De Arruda Chaves, E; de Montjoye, L; Doutre, M S; Du-Thanh, A; Ebo, D; Elkhalifa, S; Elmariah, S; El-Shanawany, T; Ensina, L F; Ertaş, R; Fachini Jardim Criado, R; Ferrer, M; Ferrucci, S; Fok, J S; Fomina, D; Fonacier, L; Fouda, G; Francescantonio, I; Fukunaga, A; Galvan Calle, C A; Garcia, E; Gáspár, K; Gelincik, A; Geng, S; Godse, K; Gonçalo, M; Gotua, M; Grattan, C; Grosber, M; Guidos Fogelbach, G; Guilarte, M; Guillod, R; Hamelmann, E; Hawkes, J; Hayama, K; Heuer, R; Hide, M; Hoetzenecker, W; Inomata, N; Kang, H-R; Kaplan, A; Kapp, A; Karam, M; Kasperska-Zajac, A; Katelaris, C H; Kessel, A; Khoshkhui, M; Kim, B; Kinaciyan, T; Kocatürk, E; Kolacinska-Flont, M; Kolkhir, P; Konstantinou, G N; Kosnik, M; Krasowska, D; Kulthanan, K; Kumaran, M S; Kuprys-Lipinska, I; Labrador, M; Larco, J I; Larenas-Linnemann, D; Latysheva, E; Lazaridou, E; Li, P H; Lima, H; Lippert, U; Magerl, M; Makris, M; Alves Marcelino, J; Marzano, A V; Medina, I; Meshkova, R; Micallef, D; Mohammed Ali, R; Mortz, C G; Munoz, M; Oude Elberink, H N G; Nakonechna, A; Nasr, I; Nast, A; Netchiporouk, E; Nettis, E; Nieto, S; Ogueta Canales, I; Okas, T-L; Orfali, R L; Özkaya, E; Parisi, C; Pennitz, A; Pawankar, R; Pereira, M P; Peter, J; Petkova, E; Pigatto, P D; Podder, I; Popov, T; Porebski, G; Pyatilova, P; Ramon, G D; Ratti Sisa, H A; Recto, M; Ress, K; Ridge, K; Riedl, M; Ritchie, C; Rosario Filho, N; Rosmaninho, I; Rudenko, M; Rukhadze, M; Rutkowski, K; Sabato, V; Sahiner, U M; Saini, S; Saleh Al Sabbagh, F; Salman, A; Salvo, F; Sanchez, J; Santucci, A; Schliemann, S; Schmid-Grendelmeier, P; Sekerel, B E; Serpa, F; Sheikh, F; Sheikh, J; Shendi, H; Siebenhaar, F; Sonomjamts, M; Soria, A; Sousa Pinto, B; Staevska, M; Staubach, P; Stephan, M; Stevanovic, K; Stingeni, L; Stobiecki, M; Su Küçük, Ö; Sussman, G; Szegedi, A; Takahagi, S; Tanaka, A; Teovska Mitrevska, N; Thomsen, S F; Toubi, E; Tsatsou, F; Turk, M; Vadasz, Z; Valerieva, A; Valle, S; Doorn, M V; Veleiro Perez, B; Vera Ayala, C E; Vestergaard, C; Vieira, R J; Maruta, C W; Wedi, B; Werner, R N; Yap, E W Y; Xepapadaki, P; Xiang, Y; Ye, Y-M; Yong, P; Yosipovitch, G; Zalewska-Janowska, A Z J; Zeyen, C; Zhao, Z; Metz, M; Giménez-Arnau, A M
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
PMID: 41649409
ISSN: 1398-9995
CID: 6000592

Associations of neighborhood deprivation and household income during pregnancy on child externalizing and internalizing problems

Hu, Yunzhe; Collazo Vargas, Julianna I; Hockett, Christine; Ziegler, Katherine; Brito, Natalie H; Akbaryan, Anahid; Costello, Lauren A; Elliott, Amy J; Fifer, William P; Morales, Santiago; Shuffrey, Lauren C
Socioeconomic disadvantage has been established as a key risk factor for adverse child behavioral outcomes. Understanding how individual components of socioeconomic status (SES) interact with each other can elucidate protective factors and inform interventions and policies to promote positive developmental outcomes. This study examined the interactive effects of prenatal household income and neighborhood deprivation on child externalizing and internalizing problems (N = 793; M
PMCID:12888081
PMID: 41645600
ISSN: 1469-2198
CID: 6000512

Tolerance and Tachyphylaxis to Medications for Attention-Deficit/Hyperactivity Disorder (ADHD): A Systematic Review of Empirical Studies

Smith, Christopher; Walker, Hollie; Parlatini, Valeria; Cortese, Samuele
BACKGROUND AND OBJECTIVE/OBJECTIVE:Individuals with attention-deficit/hyperactivity disorder, their families and clinicians may report worsening symptoms despite compliant use of medication, suggesting potential tolerance, but evidence remains conflicting. Some studies have also suggested tachyphylaxis, or acute tolerance, though research is limited. We conducted the first systematic review of empirical studies focussing on tolerance/tachyphylaxis to attention-deficit/hyperactivity disorder medication to clarify their potential clinical relevance. METHODS:As registered on PROSPERO (CRD42024594759), we searched PubMed, OVID (including PsychInfo and MEDLINE) and Web of Knowledge up to 1 September, 2024, and assessed the risk of bias using National Institutes of Health quality assessment tools. RESULTS:The identified 17 studies were either interventional or observational, and varied greatly in design and duration. Four investigated tachyphylaxis, nine tolerance to the subjective and behavioural effects, and four tolerance to cardiovascular effects. We found preliminary evidence of tachyphylaxis to the affective or behavioural effects of stimulants, as well as tolerance to the subjective effects of d-amphetamine, such as drug liking and excitation, in neurotypical volunteers in the short term. Conversely, there was little or no evidence for tolerance to the therapeutic or cardiovascular effects of attention-deficit/hyperactivity disorder medication in clinical settings in the longer term. Quality was rated as low in most studies because of small sample sizes and methodological limitations. CONCLUSIONS:Overall, these results do not support the hypothesis that tolerance commonly develops to the therapeutic effects of attention-deficit/hyperactivity disorder medication, although robustly designed longitudinal studies are needed to provide more conclusive evidence. Clinicians may consider other potential explanations for reduced therapeutic effects over time, including natural fluctuations of symptoms, limited compliance, life events and co-occurrent mental health conditions.
PMID: 41627718
ISSN: 1179-1934
CID: 5999562

Intrauterine SARS-CoV-2 Exposure and Infant Neurodevelopment through 18 Months of Age: Findings from the RECOVER Pregnancy Study

Flaherman, Valerie J; Reeder, Harrison T; Martin-Herz, Susanne P; Gallagher, Richard; Cohen, Alison K; Brown, Heather-Elizabeth; Clifton, Rebecca G; Fischbein, Nicole; Foulkes, Andrea S; Jacoby, Vanessa L; Jain, Nita; Beamon, Carmen J; Bahtiyar, Mert Ozan; Chang, Ann; Costantine, Maged M; Irving, Angelique Cruz; Gibson, Kelly S; Hoffman, M Camille; Hoffman, Matthew K; Hughes, Brenna L; Katz, Stuart D; Laleau, Victoria; Mendez-Figueroa, Hector; Monteiro, Jonathan; Okumura, Megumi; Pacheco, Luis D; Palomares, Kristy T S; Parry, Samuel; Plunkett, Beth A; Reddy, Uma M; Rouse, Dwight J; Saade, George R; Sandoval, Grecio J; Simhan, Hyagriv N; Skupski, Daniel W; Sowles, Amber; Thorp, John M; Tita, Alan T N; Weiner, Steven J; Wiegand, Samantha; Yee, Lynn M; Gross, Rachel S; Metz, Torri D; ,
OBJECTIVE:To assess associations between exposure to intrauterine SARS-CoV-2 and subsequent child neurodevelopment in a large, diverse cohort with confirmation of maternal SARS-CoV-2 status. STUDY DESIGN/METHODS:edition (ASQ-3) and at 18 months with the ASQ Social-Emotional (ASQ-SE) and the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). We compared exposed and unexposed infants' ASQ-3 total and subdomain scores, ASQ-SE and M-CHAT-R scores, and proportions meeting published referral thresholds, using multivariable linear and logistic regression. RESULTS:Among 1179 participants enrolled, 1008 (85.5%) had exposure, with 806 (80.0%) exposed during Omicron predominance. Of those with known timing, 349 (41.4%) and 295 (35.0%) were exposed in the second and third trimesters of pregnancy respectively. Exposure was not associated with differences in ASQ-3 (adjusted difference: -0.61, 95% CI: -10.03, 8.81) or ASQ-3 subdomains at 12 months, ASQ-SE at 18 months (adjusted difference: 0.19, 95% CI: -4.02, 4.41), or M-CHAT-R scores. Findings were similar for proportions meeting referral thresholds, and when stratified by variant or by trimester. CONCLUSIONS:In this multicenter cohort largely exposed since Omicron and in second or third trimester, intrauterine SARS-CoV-2 exposure was not associated with neurodevelopmental screening outcomes through 18 months of age. Further assessments of the impact of intrauterine SARS-CoV-2 on neurodevelopment beyond 18 months of age are needed.
PMID: 41565007
ISSN: 1097-6833
CID: 5988452

Two axes of white matter development

Luo, Audrey C; Meisler, Steven L; Sydnor, Valerie J; Alexander-Bloch, Aaron; Bagautdinova, Joëlle; Barch, Deanna M; Bassett, Dani S; Davatzikos, Christos; Franco, Alexandre R; Goldsmith, Jeff; Gur, Raquel E; Gur, Ruben C; Hu, Fengling; Jaskir, Marc; Kiar, Gregory; Keller, Arielle S; Larsen, Bart; Mackey, Allyson P; Milham, Michael P; Roalf, David R; Shafiei, Golia; Shinohara, Russell T; Somerville, Leah H; Weinstein, Sarah M; Yeatman, Jason D; Cieslak, Matthew; Rokem, Ariel; Satterthwaite, Theodore D
Despite decades of neuroimaging research, how white matter develops along the length of major tracts in humans remains unknown. Here, we identify fundamental patterns of white matter maturation by examining developmental variation along major, long-range cortico-cortical tracts in youth ages 5-23 years using diffusion MRI from three large-scale, cross-sectional datasets (total N = 2716). Across datasets, we delineate two replicable axes of human white matter development. First, we find a deep-to-superficial axis, in which superficial tract regions near the cortical surface exhibit greater age-related change than deep tract regions. Second, we demonstrate that the development of superficial tract regions aligns with the cortical hierarchy defined by the sensorimotor-association axis, with tract ends adjacent to sensorimotor cortices maturing earlier than those adjacent to association cortices. These results reveal developmental variation along tracts that conventional tract-average analyses have previously obscured, challenging the implicit assumption that white matter tracts mature uniformly along their length. Such developmental variation along tracts may have functional implications, including mitigating ephaptic coupling in densely packed deep tract regions and tuning neural synchrony through hierarchical development in superficial tract regions - ultimately refining neural transmission in youth.
PMID: 41578121
ISSN: 2041-1723
CID: 5988952

External trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial

Conti, Aldo Alberto; Bozhilova, Natali; Eraydin, Irem Ece; Stringer, Dominic; Johansson, Lena; Marhenke, Robert; Bilbow, Andrea; El Masri, Sahid; Hyde, Joshua; Giaroli, Giovanni; Liang, Holan; Fiori, Federico; Mehta, Mitul Ashok; Santosh, Paramala; Carter, Ben; Cortese, Samuele; Rubia, Katya
External trigeminal nerve stimulation (TNS) received US Food and Drug Administration clearance in 2019 as the first device-based, non-pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), based on a small pilot sham-controlled randomized controlled trial (RCT) that reported symptom improvement in 62 children with ADHD. Here we conducted a confirmatory multicenter, double-blind, randomized, sham-controlled, parallel-group, phase 2b RCT to investigate short-term and long-term efficacy (6 months) of real versus sham TNS in 150 children and adolescents with ADHD. Participants were randomized to receive real TNS (n = 75, mean age (s.d.) = 12.6 (2.8) years) or sham TNS (n = 75, mean age (s.d.) = 12.6 (2.8) years) nightly for approximately 9 hours for 4 weeks. Bilateral stimulation targeted V1 trigeminal branches using battery-powered electrodes applied to the forehead. Sham TNS delivered 30 seconds of stimulation per hour at lower frequency and pulse width. Intention-to-treat analysis showed no significant differential treatment effects on ADHD symptoms (primary outcome) (estimated adjusted mean difference = 0.83; 95% confidence interval: -2.47 to 4.13; P = 0.622; Cohen's d = 0.09). No serious adverse events were reported, and side effects did not differ between groups. In conclusion, TNS is a safe intervention but does not demonstrate clinical efficacy for pediatric ADHD. Trial registration: ISRCTN82129325 .
PMID: 41545587
ISSN: 1546-170x
CID: 5986792