Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11461
Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci
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
Biological pathways leading to septo-optic dysplasia: a review
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
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
Journal of the American Academy of Child and Adolescent Psychiatry. 2025:64(4):414-415.DOI: 10.1016/j.jaac.2024.09.007
Dr. Cortese et al. Reply [Letter]
Commenting on our systematic review and meta-analysis on the reporting and representation of race/ethnicity in randomized controlled trials ADHD, Jurek and Leaune thoughtfully highlighted important legal barriers that hinder the reporting of race/ethnicity data in research in some countries, focusing on France as an example. They concluded that this situation calls for a tangible action to change the status quo. Looking ahead, the question is: how should this action be implemented effectively? Given the antiracist journey that JAACAP is proudly undertaking, AACAP and JAACAP are in an ideal position to take on the challenge highlighted by Jurek and Leaune.
PMID: 39326515
ISSN: 1527-5418
CID: 5766502
Child & adolescent psychiatric clinics of North America. 2025:34(2):215-234.DOI: 10.1016/j.chc.2024.07.006
Dyadic Assessment of Caregivers and Infants, Toddlers, and Preschoolers in Clinical Practice
Dyadic assessment is an essential component of understanding a young child's mental health, providing critical information about the contexts within which they live and develop. This article describes how to observe the behaviors of a child and caregiver together, either by systematically reviewing key domains of the dyadic interaction or by using a formal observation procedure. Though challenged by issues of training and time to complete them, cultural responsiveness, and the balance of making them both naturalistic and feasible, dyadic assessments are indispensable. They can provide a foundation and jumping-off point for therapy and healing.
PMID: 40044264
ISSN: 1558-0490
CID: 5809762
Child & adolescent psychiatric clinics of North America. 2025:34(2):291-310.DOI: 10.1016/j.chc.2024.08.005
Therapeutic Interventions for Trauma-exposed Infants, Young Children, and Their Caregivers
Trauma-focused psychotherapies for infants, toddlers, and preschoolers comprise a unique subset of child trauma interventions. Given the developmental age range in question, certain characteristics of these therapies differ significantly from those for older children. This study reviews evidence-based, trauma-focused treatments for young children and their caregivers, followed by evidence-based treatments for trauma-vulnerable families with very young children that do not target trauma directly but rather reinforce attachment-related protective factors such as parental sensitivity and reflective functioning. Directions for further research are discussed.
PMID: 40044268
ISSN: 1558-0490
CID: 5809772
Prenatal Superstorm Sandy stress and postnatal affectionless control as a conjoint risk for child psychopathology
The current study investigates the conjoint effect of prenatal Superstorm Sandy stress (SS) and postnatal parenting, as measured by affectionless control (AC), in determining the risk of early childhood psychopathology. The study included 154 children (45.5% males) longitudinally tracked from ages 2-5 years. Maternal AC was assessed using the Parental Bonding Instrument. The prevalence of child diagnostic outcomes (DSM-IV anxiety disorders, phobias, and disruptive behavior disorders) was ascertained by trained clinical interviewers using maternal responses to the Preschool Age Psychiatric Assessment. Children were stratified into four groups by SS and AC status to identify synergistic effects on psychopathology exceeding the risks expected in an additive model. Children exposed to both SS and AC had over 5-fold increased risk of any anxiety disorder, a 12-fold increased risk for disruptive behavior disorders, and a nearly 5-fold increased risk of any disorder relative to the reference group of children with neither exposure. The risks of anxiety, disruptive behavior, and any disorders were synergistically greater than the sum of independent effects of the two stressors, as evident in the synergy index. Evaluation of synergistically increased risks for childhood disorders will help to identify high-risk children, which in turn could inform design of multi-level interventions to mitigate child psychopathology.
PMCID:12043322
PMID: 40308331
ISSN: 1062-1024
CID: 5833992
Statistical properties of functional connectivity MRI enrichment analysis in school-age autism research
Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations. However, there has not yet been a rigorous examination of the statistical properties of enrichment analysis when applied to fcMRI data. Establishing power for fcMRI enrichment analysis will be important for future neuropsychiatric and cognitive neuroscience study designs that plan to include this method. Here, we use realistic simulation methods, which mimic the covariance structure of fcMRI data, to examine the false positive rate and statistical power of one technique for enrichment analysis, over-representation analysis. We find it can attain high power even for moderate effects and sample sizes, and it strongly outperforms univariate analysis. The false positive rate associated with permutation testing is robust.
PMCID:11914990
PMID: 40022940
ISSN: 1878-9307
CID: 5814092
Associations Between Exercise Training, Physical Activity, Sedentary Behaviour and Mortality: An Umbrella Review of Meta-Analyses
BACKGROUND:Numerous studies support the association of exercise training, physical activity (PA) and sedentary behaviour (SB) with both mortality and morbidity outcomes. The results across studies have been inconsistent, and no umbrella reviews have yet been conducted on this topic. METHODS:We conducted an umbrella review of meta-analyses of observational studies by screening articles in PubMed/MEDLINE, EMBASE and Web of Science databases from inception to 30 April 2024. Quality appraisal of each included meta-analysis was done using the AMSTAR 2 tool, with evidence certainty evaluated based on statistical significance, study size, heterogeneity, small-study effects, prediction intervals (PI) and potential biases. RESULTS:Frothy-eight meta-analyses were included (AMSTAR 2 ratings: high 25, moderate 10, low 2 and critically low 11). No evidence was highly suggestive or convincing. Suggestive evidence linked any PA and SB to lower and higher risks of all-cause, cardiovascular and cancer mortality. Suggestive evidence indicated a significant association between self-reported and device-measured total PA (equivalent odds ratio [eOR] 0.78 [0.70-0.86] and eHR = 0.50 [0.38-0.65], respectively), self-reported leisure time PA (eHR = 0.73 [0.66-0.80]), device-measured daily steps (eHR = 0.44 [0.35-0.56]) and aerobic plus resistance training (eHR = 0.60 [0.56-0.64]) with lower all-cause mortality. Weak evidence supported links between self-reported and device-measured SB and higher mortality (eHR = 1.3 [1.22-1.38] and eHR = 2.16 [1.09-4.28], respectively). Suggestive evidence was noted for the association between self-reported leisure time PA (eHR = 0.74 [0.69-0.80]) and resistance training (eHR = 0.82 [0.81-0.84]) with cardiovascular mortality. Suggestive evidence was also found for the association between self-reported leisure time PA (eHR = 0.87 [0.83-0.91]) with cancer mortality. Associations between self-reported running time and mortality from all causes, cardiovascular diseases (CVD) and cancer did not reach statistical significance nor did the association between low skeletal muscle mass and all-cause mortality. Meta-regression analyses showed that physical activity reduces mortality risk, with age reducing the protective effects against all-cause, CVD and cancer mortality. We also found that combined exercise training (aerobic plus resistance) most effectively reduces all-cause and CVD mortality. CONCLUSIONS:Converging evidence supports that physical activity and sedentary behaviour are associated with lower and higher rates of all-cause, cardiovascular and cancer mortality. More high-quality prospective studies are needed for a better understanding of the associations between running time and also TV-viewing time and health-related outcomes.
PMCID:11880915
PMID: 40042073
ISSN: 2190-6009
CID: 5809732
Large-scale evidence of a general disease ('d') factor accounting for both mental and physical health disorders in different age groups
BACKGROUND:It is unknown whether there is a general factor that accounts for the propensity for both physical and mental conditions in different age groups and how it is associated with lifestyle and well-being. METHODS:factor, lifestyles, and well-being was further explored. RESULTS:factor scores significantly correlated with lifestyle and well-being, suggesting healthier lifestyles were associated with a reduced likelihood of physical and mental health comorbidities, which in turn improved well-being. CONCLUSIONS:Contrary to the traditional dichotomy between mental and physical conditions, our study showed a general factor underlying the comorbidity across mental and physical diseases, related to lifestyle and well-being. Our results inform the conceptualization of mental and physical illness as well as future research assessing risk and pathways of disease transmission, intervention, and prevention. Our results also provide a strong rationale for a systematic screening for mental disorders in individuals with physical conditions and vice versa, and for integrated services addressing multimorbidity.
PMID: 40066566
ISSN: 1469-8978
CID: 5808292
