Faculty Bibliography
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school:SOM
Department/Unit:Child and Adolescent Psychiatry
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11268
Raynaud Syndrome Associated with Medication for Attention-Deficit/Hyperactivity Disorder: A Systematic Review
BACKGROUND:Raynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature. The aim of this review is to evaluate the evidence in the published literature for Raynaud syndrome associated with medication for ADHD. METHODS:We systematically searched PubMed and Embase from inception to 12 June 2024 for articles published in English describing cases of RS in individuals treated with stimulant medication, atomoxetine, guanfacine or clonidine. Identified cases were assessed against the Naranjo Adverse Drug Reaction Scale criteria to determine the probability of a causal relationship with the medication. RESULTS:The initial search identified 197 articles. A total of 61 cases were identified from 15 case reports, 5 case series, 1 retrospective case-control study, and 1 retrospective cohort study. No randomised, controlled studies were identified. Implicated medications included methylphenidate, (dex)amfetamine and, more rarely, atomoxetine. Most cases were mild and resolved within weeks of discontinuation, dose reduction or switch to an alternative medication. A few cases associated with systemic disease were reported, leading to ulceration, gangrene and the need for amputation or revascularisation in some individuals. Assessment of 28 cases using the Naranjo criteria suggested a 'possible' causative role of ADHD medication in 13 cases, a 'probable' role in 13 cases and a 'definite' role in two cases. CONCLUSIONS:Due to the uncontrolled nature of all but one of the available studies, a causal relationship between medication for ADHD and RS could not be determined reliably. However, in view of the possibility of severe sequelae, albeit in rare cases, routine monitoring for signs of RS is recommended in individuals treated with CNS stimulants or atomoxetine, especially when initiating treatment or increasing the dose. Large database studies in which individuals act as their own controls should be conducted to clarify any association between treatment with these medications and RS, controlling for confounding factors.
PMID: 39875750
ISSN: 1179-1934
CID: 5780812
The Utilization of Navigation and Emerging Technologies With Endoscopic Spine Surgery: A Narrative Review
Endoscopic spine surgery (ESS) is growing in popularity worldwide. An expanding body of literature demonstrates rapid functional recovery with reduced morbidity compared to open techniques. Both full endoscopic spine surgery, or uniportal endoscopy, and unilateral biportal endoscopy (UBE) can be employed in conjunction with various navigation and enabling technologies for assistance with localization of anatomic orientation and assessment of the intraoperative target spinal pathology. This review article describes various navigation technologies in ESS, including 2-dimensional (2D) fluoroscopic imaging, 2D fluoroscopic navigation, 3-dimensional C-arm navigation, augmented reality, and spinal robotics. Employment of enabling navigation and emerging technology with the registration of patient-specific anatomy enables clear delineation of anatomic landmarks and facilitation of a successful procedure. Additionally, avoidance of common pitfalls during use of navigation systems in ESS is discussed in this review.
PMCID:12010863
PMID: 40211520
ISSN: 2586-6583
CID: 5866262
Scoping Review and Clinical Guidance: Disparities in the Care of Youth With Agitation or Aggression in the Emergency Department
OBJECTIVE/UNASSIGNED:This scoping review aims to summarize the current state of research literature on disparities in the care of youth with agitation or aggression in the emergency department (ED), including referral, assessment, diagnosis, use of pharmacologic interventions, and use of restraint and seclusion. METHOD/UNASSIGNED:This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) extension for scoping reviews searching PubMed and PsycINFO databases (May 1, 2013 through May 5, 2023) for studies that reported disparities in the care of youth with agitation or aggression in the pediatric ED. RESULTS/UNASSIGNED:Disparities in the care of youth with agitation or aggression in the ED have been documented for race, sex, age, developmental status, and insurance status. There are no data available on disparities in ED-based care of youth with agitation or aggression based on gender identity and/or presentation, sexual orientation, socioeconomic status (SES), systems involvement (including child welfare, foster care, juvenile justice), or language proficiency. CONCLUSION/UNASSIGNED:Although there are some data on disparities in the care of youth with agitation or aggression the ED documented for race, sex, age, developmental status, and insurance status, further work in this area is needed. Actionable steps to address mental health disparities in the pediatric ED are discussed. STUDY PREREGISTRATION INFORMATION/UNASSIGNED:Disparities in the Care of Youth with Agitation or Aggression in the Emergency Department: A Scoping Review and Clinical Guidance; https://osf.io/eg7tk. DIVERSITY & INCLUSION STATEMENT/UNASSIGNED:One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
PMCID:11914914
PMID: 40109489
ISSN: 2949-7329
CID: 5813492
Journal of the American Academy of Child and Adolescent Psychiatry. 2025:64(3):309-311.DOI: 10.1016/j.jaac.2024.07.931
Reflections on Best Practices for Evidence Synthesis in Youth Mental Health for Low- and Middle-Income Countries [Letter]
We read with interest the paper "Meta-analysis: The Effectiveness of Youth Psychotherapy Interventions in Low- and Middle-Income Countries" by Venturo-Conerly et al. (2023).1 The paper presents results on the effectiveness of youth psychotherapies in low- and middle-income countries (LMICs) from a systematic review and meta-analysis using rigorous, highly regarded methods. The authors should be commended for taking on this important subject. However, we feel that the paper needs to be situated in the backdrop of a few concerns that we believe are important for LMIC geographies. In our reply, we mainly focus on the finding that interventions developed in high-income countries (HIC) were more effective if not adapted to local conditions, suggesting that non-culturally adapted interventions had better outcomes than culturally adapted ones. This, as the authors note, seems counterintuitive.
PMID: 39577489
ISSN: 1527-5418
CID: 5758952
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
Familial confounding in the associations between maternal health and autism
Evidence suggests that maternal health in pregnancy is associated with autism in the offspring. However, most diagnoses in pregnant women have not been examined, and the role of familial confounding remains unknown. Our cohort included all children born in Denmark between 1998 and 2015 (n = 1,131,899) and their parents. We fitted Cox proportional hazard regression models to estimate the likelihood of autism associated with each maternal prenatal ICD-10 diagnosis, accounting for disease chronicity and comorbidity, familial correlations and sociodemographic factors. We examined the evidence for familial confounding using discordant sibling and paternal negative control designs. Among the 1,131,899 individuals in our sample, 18,374 (1.6%) were diagnosed with autism by the end of follow-up. Across 236 maternal diagnoses we tested (prevalence ≥0.1%), 30 were significantly associated with autism after accounting for sociodemographic factors, disorder chronicity and comorbidity, and correction for multiple testing. This included obstetric, cardiometabolic and psychiatric disorders (for example, diabetes in pregnancy (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08-1.31) and depression (HR 1.49, 95% CI 1.27-1.75)), previously shown to be associated with autism. Family-based analyses provided strong evidence for familial confounding in most of the observed associations. Our findings indicate pervasive associations between maternal health in pregnancy and offspring autism and underscore that these associations are largely attributable to familial confounding.
PMID: 39891002
ISSN: 1546-170x
CID: 5781342
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
Journal of the American Academy of Child and Adolescent Psychiatry. 2025:64(3):346-361.DOI: 10.1016/j.jaac.2024.05.023
Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life
OBJECTIVE:We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to understand whether this effect differs between stimulants and nonstimulants. METHOD/METHODS:February 2023 (https://med-adhd.org/), we identified randomized controlled trials (RCTs) of ADHD medications for individuals aged 6 years or more with a diagnosis of ADHD based on the DSM (from third to fifth editions) or the International Classification of Diseases (ICD; ninth or tenth revision), reporting data on QoL (measured with a validated scale). The risk of bias for each RCTs was assessed using the Cochrane Risk of Bias tool 2. Multilevel meta-analytic models were conducted with R 4.3.1. RESULTS:We included 17 RCTs (5,388 participants in total; 56% randomized to active medication) in the meta-analyses. We found that amphetamines (Hedge's g = 0.51, 95% CI = 0.08, 0.94), methylphenidate (0.38; 0.23, 0.54), and atomoxetine (0.30; 0.19, 0.40) were significantly more efficacious than placebo in improving QoL in people with ADHD, with moderate effect size. For atomoxetine, these effects were not moderated by the length of intervention, and did not differ between children/adolescents and adults. CONCLUSION/CONCLUSIONS:In addition to being efficacious in reducing ADHD core symptom severity, both stimulant and nonstimulant medications are efficacious in improving QoL in people with ADHD, albeit with lower effect sizes. Future research should explore whether, and to what degree, combining pharmacological and nonpharmacological interventions is likely to further improve QoL in people with ADHD. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:From a prior dataset of a network meta-analysis, 17 randomized controlled trials (RCTs) were included in a meta-analysis to investigate if attention-deficit/hyperactivity disorder (ADHD) medication improves quality of life (QoL) in people with ADHD. The analysis showed that medications such as amphetamines, methylphenidate, and atomoxetine improved QoL compared to placebo, with moderate effect sizes. This study underscores the importance of ADHD medications, both stimulants and nonstimulants, not only in alleviating core ADHD symptoms but also in enhancing overall QoL for individuals with ADHD. STUDY PREREGISTRATION INFORMATION/UNASSIGNED:Effects of pharmacological treatment for ADHD on quality of life: a systematic review and meta-analysis; https://osf.io/; qvgps.
PMID: 38823477
ISSN: 1527-5418
CID: 5809572
A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research
INTRODUCTION/UNASSIGNED:Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes. METHODS/UNASSIGNED:To better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents. RESULTS/UNASSIGNED:While these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research. CONCLUSIONS/UNASSIGNED:Ideally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.
PMCID:12060849
PMID: 40351554
ISSN: 2831-4433
CID: 5843892
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
