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Cross-sectional and Longitudinal Associations of Anxiety and Irritability With Adolescents' Neural Responses to Cognitive Conflict

Cardinale, Elise M; Bezek, Jessica; Morales, Santiago; Filippi, Courtney; Smith, Ashley R; Haller, Simone; Valadez, Emilio A; Harrewijn, Anita; Phillips, Dominique; Chronis-Tuscano, Andrea; Brotman, Melissa A; Fox, Nathan A; Pine, Daniel S; Leibenluft, Ellen; Kircanski, Katharina
BACKGROUND:Psychiatric symptoms are commonly comorbid in childhood. The ability to disentangle unique and shared correlates of comorbid symptoms facilitates personalized medicine. Cognitive control is implicated broadly in psychopathology, including in pediatric disorders characterized by anxiety and irritability. To disentangle cognitive control correlates of anxiety versus irritability, the current study leveraged both cross-sectional and longitudinal data from early childhood into adolescence. METHODS:For this study, 89 participants were recruited from a large longitudinal research study on early-life temperament to investigate associations of developmental trajectories of anxiety and irritability symptoms (from ages 2 to 15) as well as associations of anxiety and irritability symptoms measured cross-sectionally at age 15 with neural substrates of conflict and error processing assessed at age 15 using the flanker task. RESULTS:Results of whole-brain multivariate linear models revealed that anxiety at age 15 was uniquely associated with decreased neural response to conflict across multiple regions implicated in attentional control and conflict adaptation. Conversely, irritability at age 15 was uniquely associated with increased neural response to conflict in regions implicated in response inhibition. Developmental trajectories of anxiety and irritability interacted in relation to neural responses to both error and conflict. CONCLUSIONS:Our findings suggest that neural correlates of conflict processing may relate uniquely to anxiety and irritability. Continued cross-symptom research on the neural correlates of cognitive control could stimulate advances in individualized treatment for anxiety and irritability during child and adolescent development.
PMID: 35358745
ISSN: 2451-9030
CID: 5364812

Children's and adolescents' rising animal-source food intakes in 1990-2018 were impacted by age, region, parental education and urbanicity

Miller, V; Webb, P; Cudhea, F; Zhang, J; Reedy, J; Shi, P; Erndt-Marino, J; Coates, J; Micha, R; Mozaffarian, D; Bas, M; Ali, J H; Abumweis, S; Krishnan, A; Misra, P; Hwalla, N C; Janakiram, C; Liputo, N I; Musaiger, A; Pourfarzi, F; Alam, I; DeRidder, K; Termote, C; Memon, A; Turrini, A; Lupotto, E; Piccinelli, R; Sette, S; Anzid, K; Vossenaar, M; Mazumdar, P; Rached, I; Rovirosa, A; Zapata, M E; Asayehu, T T; Oduor, F; Boedecker, J; Aluso, L; Ortiz-Ulloa, J; Meenakshi, J V; Castro, M; Grosso, G; Waskiewicz, A; Khan, U S; Thanopoulou, A; Malekzadeh, R; Calleja, N; Ocke, M; Etemad, Z; Nsour, M A; Waswa, L M; Nurk, E; Arsenault, J; Lopez-Jaramillo, P; Sibai, A M; Damasceno, A; Arambepola, C; Lopes, C; Severo, M; Lunet, N; Torres, D; Tapanainen, H; Lindstrom, J; Virtanen, S; Palacios, C; Roos, E; Agdeppa, I A; Desnacido, J; Capanzana, M; Misra, A; Khouw, I; Ng, S A; Delgado, E G; Caballero, M; Otero, J; Lee, H -J; Koksal, E; Guessous, I; Lachat, C; De, Henauw S; Rahbar, A R; Tedstone, A; Naska, A; Mathee, A; Ling, A; Tedla, B; Hopping, B; Ginnela, B; Leclercq, C; Duante, C; Haerpfer, C; Hotz, C; Pitsavos, C; Rehm, C; van, Oosterhout C; Cerdena, C; Bradshaw, D; Trichopoulos, D; Gauci, D; Fernando, D; Sygnowska, E; Vartiainen, E; Farzadfar, F; Zajkas, G; Swan, G; Ma, G; Pekcan, G; Ibrahim, H M; Sinkko, H; Barbieri, H E; Sioen, I; Myhre, J; Gaspoz, J -M; Odenkirk, J; Bundhamcharoen, K; Nelis, K; Zarina, K; Biro, L; Johansson, L; Steingrimsdottir, L; Riley, L; Yap, M; Inoue, M; Szabo, M; Ovaskainen, M -L; Lee, M -S; Chan, M F; Cowan, M; Kandiah, M; Kally, O; Jonsdottir, O; Palmer, P; Vollenweider, P; Orfanos, P; Asciak, R; Templeton, R; Don, R; Yaakub, R; Selamat, R; Yusof, S; Al-Zenki, S; Hung, S -Y; Beer-Borst, S; Wu, S; Lukito, W; Hadden, W; Becker, W; Cao, X; Ma, Y; Lai, Y; Hjdaud, Z; Ali, J; Gravel, R; Tao, T; Veerman, J L; Chiplonkar, S; Arici, M; Ngoan, L T; Panagiotakos, D; Li, Y; Trichopoulou, A; Barengo, N; Khadilkar, A; Ekbote, V; Mohammadifard, N; Kovalskys, I; Laxmaiah, A; Rachakulla, H; Rajkumar, H; Meshram, I; Avula, L; Arlappa, N; Hemalatha, R; lacoviello, L; Bonaccio, M; Costanzo, S; Martin-Prevel, Y; Castetbon, K; Jitnarin, N; Hsieh, Y -T; Olivares, S; Tejeda, G; Hadziomeragic, A; de, Moura Souza A; Pan, W -H; Huybrechts, I; de, Brauw A; Moursi, M; Maghroun, M; Zeba, A N; Sarrafzadegan, N; Keinan-Boker, L; Goldsmith, R; Shimony, T; Jordan, I; Mastiholi, S C; Mwangi, M; Kombe, Y; Bukania, Z; Alissa, E; Al-Daghri, N; Sabico, S; Gulliford, M; Diba, T S; Oh, K; Kweon, S; Park, S; Cho, Y; Al-Hooti, S; Luangphaxay, C; Douangvichit, D; Siengsounthone, L; Marques-Vidal, P; Rybak, C; Luke, A; Piaseu, N; Rojroongwasinkul, N; Sundram, K; Baykova, D; Abedi, P; Sandjaja, S; Fadzil, F; Bukhary, N B I; Bovet, P; Chen, Y; Sawada, N; Tsugane, S; Rangelova, L; Petrova, S; Duleva, V; Lindroos, A K; Sipinen, J P; Moraeus, L; Bergman, P; Siamusantu, W; Szponar, L; Chang, H -Y; Sekiyama, M; Le, Nguyen Bao K; Nagalla, B; Polasa, K; Boindala, S; El, Ati J; Silva, I R; Dommarco, J R; Barquera, S; Ramirez, S R; Illescas-Zarate, D; Sanchez-Romero, L M; Ikeda, N; Zaghloul, S; Houshiar-rad, A; Mohammadi-Nasrabadi, F; Abdollahi, M; Chuah, K -A; Mahdy, Z A; Eldridge, A; Ding, E L; Kruger, H; Henjum, S; Fernandez, A; Suarez-Ortegon, M F; Hamad, N A; Janska, V; Tayyem, R; Mirmiran, P; Kelishadi, R; Lemming, E W; Richter, A; Mensink, G; Wieler, L; Hoffman, D; Salanave, B; Kim, C -I; Kuriyan-Raj, R; Swaminathan, S; Garriguet, D; Dastgiri, S; Vaask, S; Karupaiah, T; Zohoori, F V; Esteghamati, A; Hashemian, M; Noshad, S; Mwaniki, E; Yakes-Jimenez, E; Chileshe, J; Mwanza, S; Marques, L L; Preston, A M; Aguero, S D; Oleas, M; Posada, L; Ochoa, A; Shamsuddin, K; Shariff, Z M; Jan, Bin Jan Mohamed H; Manan, W; Nicolau, A; Tudorie, C; Poh, B K; Abbott, P; Pakseresht, M; Sharma, S; Strand, T; Alexy, U; Nothlings, U; Carmikle, J; Brown, K; Koster, J; Waidyatilaka, I; Lanerolle, P; Jayawardena, R; Long, J M; Hambidge, K M; Krebs, N F; Haque, A; Keding, G B; Korkalo, L; Erkkola, M; Freese, R; Eleraky, L; Stuetz, W; Thorsdottir, I; Gunnarsdottir, I; Serra-Majem, L; Moy, F M; Anderson, S; Jeewon, R; Zugravu, C A; Adair, L; Ng, S W; Skeaff, S; Marchioni, D; Fisberg, R; Henry, C; Ersino, G; Zello, G; Meyer, A; Elmadfa, I; Mitchell, C; Balfour, D; Geleijnse, J M; Manary, M; El-kour, T; Nikiema, L; Mirzaei, M; Hakeem, R
Animal-source foods (ASF) provide nutrition for children and adolescents' physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world's child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15-19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.
Copyright
EMBASE:2022707858
ISSN: 2662-1355
CID: 5515632

Annual Research Review: Perspectives on progress in ADHD science - from characterization to cause

Sonuga-Barke, Edmund J S; Becker, Stephen P; Bölte, Sven; Castellanos, Francisco Xavier; Franke, Barbara; Newcorn, Jeffrey H; Nigg, Joel T; Rohde, Luis Augusto; Simonoff, Emily
The science of attention-deficit/hyperactivity disorder (ADHD) is motivated by a translational goal - the discovery and exploitation of knowledge about the nature of ADHD to the benefit of those individuals whose lives it affects. Over the past fifty years, scientific research has made enormous strides in characterizing the ADHD condition and in understanding its correlates and causes. However, the translation of these scientific insights into clinical benefits has been limited. In this review, we provide a selective and focused survey of the scientific field of ADHD, providing our personal perspectives on what constitutes the scientific consensus, important new leads to be highlighted, and the key outstanding questions to be addressed going forward. We cover two broad domains - clinical characterization and, risk factors, causal processes and neuro-biological pathways. Part one focuses on the developmental course of ADHD, co-occurring characteristics and conditions, and the functional impact of living with ADHD - including impairment, quality of life, and stigma. In part two, we explore genetic and environmental influences and putative mediating brain processes. In the final section, we reflect on the future of the ADHD construct in the light of cross-cutting scientific themes and recent conceptual reformulations that cast ADHD traits as part of a broader spectrum of neurodivergence.
PMID: 36220605
ISSN: 1469-7610
CID: 5360952

The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications

Cortese, Samuele; McGinn, Katherine; Højlund, Mikkel; Apter, Alan; Arango, Celso; Baeza, Immaculada; Banaschewski, Tobias; Buitelaar, Jan; Castro-Fornieles, Josefina; Coghill, David; Cohen, David; Grünblatt, Edna; Hoekstra, Pieter J; James, Anthony; Jeppesen, Pia; Nagy, Péter; Pagsberg, Anne Katrine; Parellada, Mara; Persico, Antonio M; Purper-Ouakil, Diane; Roessner, Veit; Santosh, Paramala; Simonoff, Emily; Stevanovic, Dejan; Stringaris, Argyris; Vitiello, Benedetto; Walitza, Susanne; Weizman, Abraham; Wohlfarth, Tamar; Wong, Ian C K; Zalsman, Gil; Zuddas, Alessandro; Moreno, Carmen; Solmi, Marco; Correll, Christoph U
We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.
PMID: 37001575
ISSN: 1873-7528
CID: 5463482

Identification and treatment of individuals with attention-deficit/hyperactivity disorder and substance use disorder: An expert consensus statement

Young, Susan; Abbasian, Cyrus; Al-Attar, Zainab; Branney, Polly; Colley, Bill; Cortese, Samuele; Cubbin, Sally; Deeley, Quinton; Gudjonsson, Gisli Hannes; Hill, Peter; Hollingdale, Jack; Jenden, Steve; Johnson, Joe; Judge, Deborah; Lewis, Alexandra; Mason, Peter; Mukherjee, Raja; Nutt, David; Roberts, Jane; Robinson, Fiona; Woodhouse, Emma; Cocallis, Kelly
Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with substance use (SU) and/or substance use disorder (SUD). Individuals with concurrent ADHD and SU/SUD can have complex presentations that may complicate diagnosis and treatment. This can be further complicated by the context in which services are delivered. Also, when working with young people and adults with co-existing ADHD and SU/SUD, there is uncertainty among healthcare practitioners on how best to meet their needs. In February 2022, the United Kingdom ADHD Partnership hosted a meeting attended by multidisciplinary experts to address these issues. Following presentations providing attendees with an overview of the literature, group discussions were held synthesizing research evidence and clinical experience. Topics included: (1) A review of substances and reasons for use/misuse; (2) identification, assessment and treatment of illicit SU/SUD in young people and adults with ADHD presenting in community services; and (3) identification, assessment and treatment of ADHD in adults presenting in SU/SUD community and inpatient services. Dis-cussions highlighted inter-service barriers and fragmentation of care. It was concluded that a multimodal and multi-agency approach is needed. The consensus group generated a table of practice recommendations providing guidance on: identification and assessment; pharmacological and psychological treatment; and multi-agency interventions.
PMCID:10075023
PMID: 37033892
ISSN: 2220-3206
CID: 5470512

Barriers and Facilitators to Father's Engagement in a Depression and Alcohol Use Intervention in Kenya: Father, Family, and Community Factors

Giusto, Ali; Jaguga, Florence; Pereira-Sanchez, Victor; Rono, Wilter; Triplett, Noah; Rukh-E-Qamar, Hani; Parker, Mattea; Wainberg, Milton L
In Kenya, there is a treatment gap for depression and alcohol use that is especially large for fathers, which has consequences for families. While treatments exist, there are challenges to implementation. This study aimed to understand barriers and facilitators to implementing a treatment for fathers' depression and alcohol use in Eldoret, Kenya. Guided by the Consolidated Framework for Implementation Research and the Integrated Sustainability Framework, we conducted 18 key informant interviews and 7 focus group discussions (31 total participants) with stakeholders in Eldoret (hospital leaders, policy makers, mental health providers, community leaders, fathers, lay providers, and patients previously engaged in treatment). Interviews were analyzed using the framework method; themes were matrixed by framework domains. Participants identified barriers and facilitators, and opportunities for implementation, in the following domains: innovation, outer setting, inner setting, individual, sustainability, and characteristics of systems. Barriers included a lack of resources, stigma, masculine norms, cost of services, and alcohol dependence. Facilitators included community buy-in, family support, providers with lived experience, government support, and relevant treatment content. Findings will inform implementation strategy development for an intervention for fathers with depression and alcohol use, and family problems with local relevance and scalable potential.
PMCID:10048967
PMID: 36981739
ISSN: 1660-4601
CID: 5463252

Telehealth Treatment of Behavior Problems in Young Children With Developmental Delay: A Randomized Clinical Trial

Bagner, Daniel M; Berkovits, Michelle D; Coxe, Stefany; Frech, Natalie; Garcia, Dainelys; Golik, Alexandra; Heflin, Brynna H; Heymann, Perrine; Javadi, Natalie; Sanchez, Amanda L; Wilson, Maria K; Comer, Jonathan S
IMPORTANCE:Early behavior problems in children with developmental delay (DD) are prevalent and impairing, but service barriers persist. Controlled studies examining telehealth approaches are limited, particularly for children with DD. OBJECTIVE:To evaluate the efficacy of a telehealth parenting intervention for behavior problems in young children with DD. DESIGN, SETTING, AND PARTICIPANTS:A randomized clinical trial was conducted from March 17, 2016, to December 15, 2020, in which children with DD and externalizing behavior problems were recruited from early intervention and randomly assigned to a telehealth parenting intervention or control group and evaluated through a 12-month follow-up. Most children were from ethnic or racial minoritized backgrounds. Over one-half of children were in extreme poverty or low income-need ratio categories. INTERVENTIONS:Internet-delivered parent-child interaction therapy (iPCIT), which leverages videoconferencing to provide live coaching of home-based caregiver-child interactions. Families received 20 weeks of iPCIT (provided in English or in Spanish) or referrals as usual (RAU). MAIN OUTCOMES AND MEASURES:Observational and caregiver-report measures of child and caregiver behaviors and caregiving stress were examined at preintervention, midtreatment, and postintervention and at 6- and 12-month follow-ups. RESULTS:The sample included a total of 150 children (mean [SD] age, 36.2 [1.0] months; 111 male children [74%]) and their caregivers with 75 each randomly assigned to iPCIT or RAU groups. Children receiving iPCIT relative to RAU displayed significantly lower levels of externalizing problems (postintervention Cohen d = 0.48; 6-month Cohen d = 0.49; 12-month Cohen d = 0.50) and significantly higher levels of compliance to caregiver direction after treatment. Of those children with data at postintervention, greater clinically significant change was observed at postintervention for children in the iPCIT group (50 [74%]) than for those in the RAU group (30 [42%]), which was maintained at the 6-month but not the 12-month follow-up. iPCIT did not outperform RAU in reducing caregiving stress, but caregivers receiving iPCIT, relative to RAU, showed steeper increases in proportion of observed positive parenting skills (postintervention odds ratio [OR], 1.10; 95% CI, 0.53-2.21; 6-month OR, 1.31; 95% CI, 0.61-2.55; 12-month OR, 1.64; 95% CI, 0.70-3.07) and sharper decreases in proportion of observed controlling/critical behaviors (postintervention OR, 1.40; 95% CI, 0.61-1.52; 6-month OR, 1.72; 95% CI, 0.58-1.46; 12-month OR, 2.23; 95% CI, 0.53-1.37). After treatment, iPCIT caregivers also self-reported steeper decreases in harsh and inconsistent discipline than did than RAU caregivers (postintervention Cohen d = 0.24; 6-month Cohen d = 0.26; 12-month Cohen d = 0.27). CONCLUSIONS AND RELEVANCE:Results of this randomized clinical trial provide evidence that a telehealth-delivered parenting intervention with real-time therapist coaching led to significant and maintained improvements for young children with DD and their caregivers. Findings underscore the promise of telehealth formats for expanding scope and reach of care for underserved families. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03260816.
PMID: 36622653
ISSN: 2168-6211
CID: 5761132

Robust tests for scatter separability beyond Gaussianity

Kim, Seungkyu; Park, Seongoh; Lim, Johan; Lee, Sang Han
Separability (a Kronecker product) of a scatter matrix is one of favorable structures when multivariate heavy-tailed data are collected in a matrix form, due to its parsimonious representation. However, little attempt has been made to test separability beyond Gaussianity. In this paper, we present nonparametric separability tests that can be applied to a larger class of multivariate distributions not only including elliptical distributions but also generalized elliptical distributions and transelliptical distributions. The proposed test statistic exploits robustness of Tyler's M (or Kendall's tau) estimator and a likelihood function of a scaled variable. Since its distribution is hard to specify, we approximate the p-value using a permutation procedure, whose unbiasedness is obtained from the permutation invariance of multivariate paired data. Our simulation study demonstrates the efficacy of our method against other alternatives, and we apply it to rhesus monkey data and corpus callosum data.
SCOPUS:85140138309
ISSN: 0167-9473
CID: 5350452

Protracted development of motor cortex constrains rich interpretations of infant cognition

Blumberg, Mark S; Adolph, Karen E
Cognition in preverbal human infants must be inferred from overt motor behaviors such as gaze shifts, head turns, or reaching for objects. However, infant mammals - including human infants - show protracted postnatal development of cortical motor outflow. Cortical control of eye, face, head, and limb movements is absent at birth and slowly emerges over the first postnatal year and beyond. Accordingly, the neonatal cortex in humans cannot generate the motor behaviors routinely used to support inferences about infants' cognitive abilities, and thus claims of developmental continuity between infant and adult cognition are suspect. Recognition of the protracted development of motor cortex should temper rich interpretations of infant cognition and motivate more serious consideration of the role of subcortical mechanisms in early cognitive development.
PMCID:9957955
PMID: 36681607
ISSN: 1879-307x
CID: 5457142

Xylazine in the Opioid Epidemic: A Systematic Review of Case Reports and Clinical Implications

Ayub, Shahana; Parnia, Shanli; Poddar, Karuna; Bachu, Anil K; Sullivan, Amanda; Khan, Ali M; Ahmed, Saeed; Jain, Lakshit
INTRODUCTION AND OBJECTIVES/OBJECTIVE:The opioid overdose epidemic is exacerbated by the emergence of Xylazine as an illicit drug adulterant. Xylazine, a veterinary sedative, can potentiate opioid effects while also causing toxic and potentially fatal side effects. This systematic review aims to assess the impact of Xylazine use and overdoses within the opioid epidemic context. METHOD/METHODS:A systematic search was conducted following PRISMA guidelines to identify relevant case reports, and case series related to Xylazine use. A comprehensive literature search included databases like Web of Science, PubMed, Embase, and Google Scholar, utilizing keywords and Medical Subject Headings (MeSH) terms related to Xylazine. Thirty-four articles met the inclusion criteria for this review. RESULTS:Intravenous (IV) administration was a common route for Xylazine use among various methods, including subcutaneous (SC), intramuscular (IM), and inhalation, with overall doses ranging from 40 mg to 4300 mg. The average dose in fatal cases was 1,200 mg, compared to 525 mg in non-fatal cases. Concurrent administration of other drugs, primarily opioids, occurred in 28 cases (47.5%). Intoxication was identified as a notable concern in 32 out of 34 studies, and treatments varied, with the majority experiencing positive outcomes. Withdrawal symptoms were documented in one case study, but the low number of cases with withdrawal symptoms may be attributed to factors such as a limited number of cases or individual variation. Naloxone was administered in eight cases (13.6%), and all patients recovered, although it should not be misconstrued as an antidote for Xylazine intoxication. Of the 59 cases, 21 (35.6%) resulted in fatal outcomes, with 17 involving Xylazine use in conjunction with other drugs. The IV route was a common factor in six out of the 21 fatal cases (28.6%). CONCLUSION/CONCLUSIONS:This review highlights the clinical challenges associated with Xylazine use and its co-administration with other substances, particularly opioids. Intoxication was identified as a major concern, and treatments varied across the studies, including supportive care, naloxone, and other medications. Further research is needed to explore the epidemiology and clinical implications of Xylazine use. Understanding the motivations and circumstances leading to Xylazine use, as well as its effects on users, is essential for developing effective psychosocial support and treatment interventions to address this public health crisis.
PMCID:10063250
PMID: 37009344
ISSN: 2168-8184
CID: 5449322