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New Perspectives on Non-Invasive Cerebellar Stimulation for Social and Affective Functions in Children and Adolescents

Pasca, Ludovica; Romaniello, Romina; Borgatti, Renato; Ciricugno, Andrea
Cerebellar dysfunction affects socio-affective abilities beyond motor control. Recent studies suggest that non-invasive cerebellar neurostimulation can modulate social cognition networks, offering potential therapeutic benefits for children with autism, ADHD, and mood disorders. However, its application in pediatrics remains largely unexplored. This review summarizes emerging pediatric research on cerebellar transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We discuss their mechanisms, potential benefits, and safety considerations, highlighting preliminary findings that suggest feasibility and effectiveness. Ethical concerns and technical challenges related to pediatric neuroanatomy and stimulation parameters are also addressed. While early results are promising, further clinical trials and neurophysiological studies are essential to optimize protocols and confirm long-term efficacy. Advancing our understanding of cerebellar involvement in socio-affective functions could lead to innovative rehabilitation strategies for neurodevelopmental disorders.
PMCID:12033187
PMID: 40285968
ISSN: 1473-4230
CID: 5964882

Disparities in cigarette smoking and the health of marginalized populations in the U.S.: a simulation analysis

Levy, Douglas E; Lee, Stephanie S; Qian, Yiqi; Shebl, Fatma M; Goldberg, Sydney L; Mulroy, Nora M; Anderson, Nicola K; Hyle, Emily P; Becker, Jessica E; Reddy, Krishna P
INTRODUCTION/BACKGROUND:People with low socioeconomic status (SES) or serious psychological distress (SPD) in the U.S. face ongoing and future disparities in tobacco smoking. We sought to estimate how smoking disparities contribute to disparities in life expectancy and aggregate life-years in these marginalized subpopulations. METHODS:We used the Simulation of Tobacco and Nicotine Outcomes and Policy (STOP) microsimulation model to project life expectancy as a function of subpopulation (low SES, higher SES, SPD, or non-SPD) and cigarette smoking status. Low SES was defined as having at least one of the following: income below poverty, less than high school education, or Medicaid insurance. Higher SES individuals belonged to none of these categories. SPD was defined as Kessler-6 score ≥ 13; non-SPD was a Kessler-6 score < 13. To project individual life expectancy losses from smoking, we simulated 40-year-olds stratified by gender, subpopulation (by SES or by SPD, with no change), and smoking status (current/never, with no change). To project time to reach 5% cigarette smoking prevalence (U.S.) - reflecting one tobacco "endgame" threshold - in each subpopulation, we simulated the entire subpopulations of people with low SES, higher SES, SPD, and non-SPD, incorporating corresponding distributions of gender, age, and smoking status and accounting for changes in smoking behaviors and secular smoking trends. We then estimated total life-years accumulated under status quo and alternate scenarios in which smoking dynamics in the marginalized subpopulations matched those of their less marginalized counterparts. RESULTS:The model showed that, for individuals with low SES or SPD, smoking is associated with substantial loss of life expectancy (9.8-11.5y). Marginalized subpopulations would reach 5% smoking prevalence 20y (low SES) and 17y (SPD) sooner if smoking trends mirrored their less marginalized counterparts; these differences result in 5.3 million (low SES) and 966,000 (SPD) excess life-years lost over 40y. CONCLUSIONS:Differences in cigarette smoking portend substantial ongoing and future disparities in life expectancy and time to reach 5% smoking prevalence. Reducing tobacco-related disparities in the U.S. will require an explicitly equity-focused vision, and the tobacco endgame will only be truly achieved when it includes all groups.
PMCID:12023394
PMID: 40281457
ISSN: 1471-2458
CID: 5830812

Cultural adaptation of clinic-based pediatric hiv status disclosure intervention with task shifting in Eastern Uganda

Kirabira, Joseph; Nakigudde, Janet; Huang, Keng-Yen; Ashaba, Scholastic; Nambuya, Harriet; Tozan, Yesim; Yang, Lawrence H
BACKGROUND:HIV status disclosure remains a major challenge among children living with perinatally acquired HIV with many taking treatment up to adolescence without knowing their serostatus. This non-disclosure is influenced by factors like fear of the negative consequences of disclosure. Since HIV status disclosure has been found to have good effects including improving treatment adherence and better mental health outcomes, there is a need to design interventions aimed at improving disclosure rates among children living with HIV. This study aims at adapting a clinic-based pediatric HIV status disclosure intervention and tasking shifting from healthcare workers to caregiver peer supporters in Eastern Uganda. METHODS:The adaptation process involved consultations with caregivers, healthcare workers involved in the care of children living with HIV, researchers in this field, intervention developers, and other experts and stakeholders. This was done through conducting FGDs with HCWs, caregivers, and peer supporters and consultations with researchers in the field of HIV. The original intervention manual was translated to Lusoga which is the commonly spoken dialect in this region. Collected qualitative data were analyzed using an inductive approach to develop themes and subthemes. Written informed consent will be obtained from all participants before participation in the study. RESULTS:A total of 28 participants were involved in the FGDs, while two pediatricians and two HIV researchers/specialists were consulted. Six themes were generated in relation to all suggested changes to the original manual which were related to: (1) sociocultural beliefs/norms/perceptions (5 FGDs), (2) boosting caregiver's confidence for disclosure (5FGDs), (3) disclosure mode, environment, and person (4 FGDs), (4) health facility/system related changes (3 FGDs), (5) reorganization/paraphrasing (3FGDs) and (6) age appropriateness (2FGDs). CONCLUSION/CONCLUSIONS:This study emphasized that whereas some aspects of intervention can apply to various contexts, there is a need for cross-cultural adaptation of interventions before being implemented in settings where they were not developed.
PMCID:12008972
PMID: 40253345
ISSN: 1742-6405
CID: 5829282

Beyond depression and anxiety in pediatric primary care: Current insights from the collaborative care model

De Oliveira, Roberta Guimaraes; Carroll, Ian Christopher
Collaborative Care is well accepted as an evidence-based model to manage depression and anxiety in pediatric primary care. However, symptoms of attention-deficit hyperactivity disorder (ADHD), traumatic stress, and grief are common in primary care and can also be identified by pediatricians and treated within this model. Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder with a prevalence of 10.2 %.1 Trauma-spectrum disorders are another cluster of disorders that will often be seen first by the pediatrician, and, potentially, only by the pediatrician. In some urban pediatric centers, the rate of children who have been exposed to traumatic events is as high as 90 %.2 Similarly, symptoms of grief are often first identified by the pediatrician. Considering that the COVID-19 pandemic alone has claimed >760,000 parents, custodial grandparents, and other caregivers to children in the US, the number of children and teenagers affected by trauma and loss overwhelms the mental health care system's capacity. In light of the shortage of child and adolescent psychiatrists in the United States and the increased demand for mental health services, it is essential to broaden the scope of what collaborative care initiatives can accomplish in pediatrics. This paper shares insights from a collaborative care model implemented in a New York City safety net hospital center to illustrate how ADHD, traumatic stress, and grief can be identified and managed in pediatric primary care. Lastly, we will discuss the potential for collaborative care models to increase access to care for immigrant families.
PMID: 40246637
ISSN: 1538-3199
CID: 5828842

Adenosine Makes a Scene

Scharfman, Helen E
PMCID:12003313
PMID: 40256115
ISSN: 1535-7597
CID: 5829892

Attention problems in children born very preterm: evidence from a performance-based measure

Camerota, Marie; Castellanos, Francisco Xavier; Carter, Brian S; Check, Jennifer; Helderman, Jennifer; Hofheimer, Julie A; McGowan, Elisabeth C; Neal, Charles R; Pastyrnak, Steven L; Smith, Lynne M; O'Shea, Thomas Michael; Marsit, Carmen J; Lester, Barry M
BACKGROUND:Children born very preterm (VPT) are at high risk for attention problems. This study's purpose was to describe the Conners Kiddie Continuous Performance Test (K-CPT) assessment in children born VPT, including rates of clinically elevated scores, change over time, and associations between K-CPT scores and parent reported attention problems. METHODS:We studied 305 children from a multi-site study of children born VPT who completed at least one K-CPT assessment at age 5, 6, and/or 7 years. Parent-reported ADHD symptoms and diagnosis were also collected. We calculated K-CPT completion rates, mean scores, and rates of clinically elevated scores at each timepoint. Linear mixed models examined change over time in K-CPT scores. Correlations and generalized linear models investigated associations between K-CPT scores and ADHD symptoms and diagnoses. RESULTS:K-CPT scores showed expected age-related improvements from age 5-7, with significant intra- and inter-individual variability. Up to 1/3 of children had clinically elevated attention problems and another 1/3 had subclinical elevations. K-CPT scores were modestly correlated with parent-rated ADHD symptoms and children with a parent-reported ADHD diagnosis performed worse on nearly all K-CPT metrics. CONCLUSION/CONCLUSIONS:Performance-based measures like the K-CPT can be useful for research and clinical practice in VPT populations. IMPACT/CONCLUSIONS:Attention problems are a specific area of weakness for children born very preterm. Performance-based tests of attention have benefits and drawbacks compared to parent report measures yet are understudied in this population. We examined one performance-based measure (the Conners Kiddie Continuous Performance Test [K-CPT]) in 305 children born very preterm. We observed improving task scores from age 5-7 years with significant intra- and inter-individual variability, a sizable proportion of children with clinically and subclinically elevated scores, and modest associations between K-CPT scores and parent reported attention problems. The K-CPT could be a useful clinical and research tool in this population.
PMID: 40204869
ISSN: 1530-0447
CID: 5823992

Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci

Strom, Nora I; Gerring, Zachary F; Galimberti, Marco; Yu, Dongmei; Halvorsen, Matthew W; Abdellaoui, Abdel; Rodriguez-Fontenla, Cristina; Sealock, Julia M; Bigdeli, Tim; Coleman, Jonathan R; Mahjani, Behrang; Thorp, Jackson G; Bey, Katharina; Burton, Christie L; Luykx, Jurjen J; Zai, Gwyneth; Alemany, Silvia; Andre, Christine; Askland, Kathleen D; Banaj, Nerisa; Barlassina, Cristina; Nissen, Judith Becker; Bienvenu, O Joseph; Black, Donald; Bloch, Michael H; Boberg, Julia; Børte, Sigrid; Bosch, Rosa; Breen, Michael; Brennan, Brian P; Brentani, Helena; Buxbaum, Joseph D; Bybjerg-Grauholm, Jonas; Byrne, Enda M; Cabana-Dominguez, Judit; Camarena, Beatriz; Camarena, Adrian; Cappi, Carolina; Carracedo, Angel; Casas, Miguel; Cavallini, Maria Cristina; Ciullo, Valentina; Cook, Edwin H; Crosby, Jesse; Cullen, Bernadette A; De Schipper, Elles J; Delorme, Richard; Djurovic, Srdjan; Elias, Jason A; Estivill, Xavier; Falkenstein, Martha J; Fundin, Bengt T; Garner, Lauryn; German, Chris; Gironda, Christina; Goes, Fernando S; Grados, Marco A; Grove, Jakob; Guo, Wei; Haavik, Jan; Hagen, Kristen; Harrington, Kelly; Havdahl, Alexandra; Höffler, Kira D; Hounie, Ana G; Hucks, Donald; Hultman, Christina; Janecka, Magdalena; Jenike, Eric; Karlsson, Elinor K; Kelley, Kara; Klawohn, Julia; Krasnow, Janice E; Krebs, Kristi; Lange, Christoph; Lanzagorta, Nuria; Levey, Daniel; Lindblad-Toh, Kerstin; Macciardi, Fabio; Maher, Brion; Mathes, Brittany; McArthur, Evonne; McGregor, Nathaniel; McLaughlin, Nicole C; Meier, Sandra; Miguel, Euripedes C; Mulhern, Maureen; Nestadt, Paul S; Nurmi, Erika L; O'Connell, Kevin S; Osiecki, Lisa; Ousdal, Olga Therese; Palviainen, Teemu; Pedersen, Nancy L; Piras, Fabrizio; Piras, Federica; Potluri, Sriramya; Rabionet, Raquel; Ramirez, Alfredo; Rauch, Scott; Reichenberg, Abraham; Riddle, Mark A; Ripke, Stephan; Rosário, Maria C; Sampaio, Aline S; Schiele, Miriam A; Skogholt, Anne Heidi; Sloofman, Laura G Sloofman G; Smit, Jan; Soler, Artigas María; Thomas, Laurent F; Tifft, Eric; Vallada, Homero; van Kirk, Nathanial; Veenstra-VanderWeele, Jeremy; Vulink, Nienke N; Walker, Christopher P; Wang, Ying; Wendland, Jens R; Winsvold, Bendik S; Yao, Yin; Zhou, Hang; ,; ,; ,; ,; ,; Agrawal, Arpana; Alonso, Pino; Berberich, Götz; Bucholz, Kathleen K; Bulik, Cynthia M; Cath, Danielle; Denys, Damiaan; Eapen, Valsamma; Edenberg, Howard; Falkai, Peter; Fernandez, Thomas V; Fyer, Abby J; Gaziano, J M; Geller, Dan A; Grabe, Hans J; Greenberg, Benjamin D; Hanna, Gregory L; Hickie, Ian B; Hougaard, David M; Kathmann, Norbert; Kennedy, James; Lai, Dongbing; Landén, Mikael; Le Hellard, Stéphanie; Leboyer, Marion; Lochner, Christine; McCracken, James T; Medland, Sarah E; Mortensen, Preben B; Neale, Benjamin M; Nicolini, Humberto; Nordentoft, Merete; Pato, Michele; Pato, Carlos; Pauls, David L; Piacentini, John; Pittenger, Christopher; Posthuma, Danielle; Ramos-Quiroga, Josep Antoni; Rasmussen, Steven A; Richter, Margaret A; Rosenberg, David R; Ruhrmann, Stephan; Samuels, Jack F; Sandin, Sven; Sandor, Paul; Spalletta, Gianfranco; Stein, Dan J; Stewart, S Evelyn; Storch, Eric A; Stranger, Barbara E; Turiel, Maurizio; Werge, Thomas; Andreassen, Ole A; Børglum, Anders D; Walitza, Susanne; Hveem, Kristian; Hansen, Bjarne K; Rück, Christian P; Martin, Nicholas G; Milani, Lili; Mors, Ole; Reichborn-Kjennerud, Ted; Ribasés, Marta; Kvale, Gerd; Mataix-Cols, David; Domschke, Katharina; Grünblatt, Edna; Wagner, Michael; Zwart, John-Anker; Breen, Gerome; Nestadt, Gerald; Kaprio, Jaakko; Arnold, Paul D; Grice, Dorothy E; Knowles, James A; Ask, Helga; Verweij, Karin J; Davis, Lea K; Smit, Dirk J; Crowley, James J; Scharf, Jeremiah M; Stein, Murray B; Gelernter, Joel; Mathews, Carol A; Derks, Eske M; Mattheisen, Manuel
Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.
PMCID:11071577
PMID: 38712091
CID: 5662722

Ambient Air Pollution and Depressed Mood in the National Longitudinal Study of Adolescent to Adult Health (Add Health) Wave IV

Yu, Wuyue; Thurston, George; Shao, Yongzhao; Zhang, Yian; Copeland, William E; Stein, Cheryl R
Depression is a major contributor to the global burden of disease. There is limited understanding of how environmental exposures may contribute to depression etiology. We used Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine associations between low-level ambient air pollution exposure and depressed mood in a generally healthy population of over 10,000 24-32 year olds. Annual mean PM2.5 levels in the 2008-2009 study were close to the current U.S. standard. In fully adjusted quasi-binomial logistic regression models, there were no meaningful associations between IQR increases in air pollutant and change in depressed mood status regardless of specific pollutant or moving average lags. In interaction effects models, an IQR increase in lag day 0-30 PM2.5 resulted in 1.20 (95% CI, 1.02-1.41) times higher likelihood of having depressed mood, but only for persons with chronic lung disease (interaction P=0.04); the association was null for participants without chronic lung disease (OR 0.98, 95% CI, 0.91, 1.05). Our findings suggest that among persons with a lifetime history of chronic lung disease, greater exposure to even low-level PM2.5, PM10, and sulfate may be associated with modest increases in the likelihood of having depressed mood.
PMID: 39191648
ISSN: 1476-6256
CID: 5729702

Biological pathways leading to septo-optic dysplasia: a review

Pasca, Ludovica; Politano, Davide; Morelli, Federica; Garau, Jessica; Signorini, Sabrina; Valente, Enza Maria; Borgatti, Renato; Romaniello, Romina
BACKGROUND:The precise etiology of septo-optic dysplasia (SOD) remains elusive, to date a complex interaction between genetic predisposition and prenatal exposure to environmental factors is believed to come into play. Being SOD such a heterogeneous condition, disruption of many developmental steps in the early forebrain development might occur. The knowledge of genes possibly determining SOD phenotype should be improved, therefore in this review the authors attempt to highlight the genetic pathways and genes related to this clinical condition. MAIN BODY/METHODS:Literature search was conducted and updated in November 2023, using PubMed and Google Scholar to identify primary research articles or case reports with available full text using the following search string "case reports," "humans," "septo-optic dysplasia," "optic nerve hypoplasia," with a recognized genetic diagnosis. Moreover, a review of genetic pathways with an involvement in SOD etiology was conducted. This review thus represents the authors' perspective based on selected literature. The several pathways presented might be already associated to other disease phenotypes and interplay with genes and pathways known to have a role in SOD determination. Those pathways may converge and thus, the implicated genes may function as cascading regulators at multiple levels. CONCLUSION/CONCLUSIONS:The present data suggest that genes other than HESX1, SOX2, SOX3, and OTX2 might be investigated in candidate individuals with a clinical diagnosis of SOD corresponding to the presence of at least two diagnostic criteria, particularly in the presence of additional syndromic anomalies.
PMCID:11969957
PMID: 40181463
ISSN: 1750-1172
CID: 5964912

Bahir Dar Child Development Cross-Sectional Study, Ethiopia: study protocol

Jensen, Sarah K G; Yibeltal, Kalkidan; North, Krysten; Workneh, Firehiwot; Teklehaimanot, Atsede; Abate, Betelhem Haimanot; Fasil, Nebiyou; Melka, Tizita Lemma; Chin, Theresa I; Folger, Lian V; Roy Paladhi, Unmesha; Van Dyk, Fred; Thomason, Moriah E; Grant, Patricia Ellen; Inder, Terrie; Worku, Alemayehu; Berhane, Yemane; Lee, Anne Cc
INTRODUCTION/BACKGROUND:Foundational preacademic skills are crucial for academic success and serve as predictors of socioeconomic status, income and access to healthcare. However, there is a gap in our understanding of neurodevelopmental patterns underlying preacademic skills in children across low-income and middle-income countries (LMICs). It is essential to identify primary global and regional factors that drive children's neurodevelopment in LMICs. This study aims to characterise the typical development of healthy children and factors that influence child development in Bahir Dar, Ethiopia. METHODS AND ANALYSIS/METHODS:The Bahir Dar Child Development Study is a cross-sectional study implemented in two health centres, Shimbit and Abaymado and in Felege Hiwot Comprehensive Specialized Hospital (FHCSH) in Bahir Dar, Amhara, Ethiopia. Healthy children between 6 and 60 months of age will be recruited from the health centres during vaccination visits or via community outreach. Young children aged 6-36 months will complete the Global Scale for Early Development. A battery of paper and tablet-based assessments of neurocognitive outcomes including visual and verbal reasoning, executive functions and school readiness will be completed for children aged 48-60 months. Caregivers will respond to surveys covering sociodemographic information, the child's medical history and nutrition, and psychosocial experiences including parental stress and mental health. During a second visit, participants will undergo a low-field MRI scan using the ultra-low-field point-of-care Hyperfine MRI machine at FHCSH. Analyses will examine relationships between risk and protective factors, brain volumes and neurocognitive/developmental outcomes. ETHICS AND DISSEMINATION/BACKGROUND:The study is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/lRERC/004/2023/Al/05-2024), Mass General Brigham Hospital (2022P002539) and Brown University (STUDY00000474). Findings will be disseminated via local dissemination events, international conferences and publications. TRIAL REGISTERATION NUMBER/BACKGROUND:NCT06648863.
PMCID:11969594
PMID: 40180427
ISSN: 2399-9772
CID: 5819302