Faculty Bibliography

INTRODUCTION/BACKGROUND:Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM. METHODS:Case-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer MRI) were assessed. RESULTS:Participants included 11 individuals with FRDA (4 female), median age 27y (IQR 23, 39), BMI 26.9kg/m2 (24.1, 29.4), and 24 controls (11 female), 29y (26, 39), 24.4kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA (91 vs. 83mg/dL (5.0 vs. 4.6mmol/L), p<0.05). Individuals with FRDA had lower insulin sensitivity (WBISI 2.8 vs. 5.3, p<0.01), higher post-prandial insulin secretion (insulin secretory rate iAUC 30-180 minutes, 24,652 vs. 17,858, p<0.05), and more suppressed post-prandial endogenous glucose production (-0.9% vs. 26.9% of fasting EGP, p<0.05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different. CONCLUSIONS:Lower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory, and when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.

The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.4% female) in the Millennium Cohort Study (N = 10,647). Survey weights were used to account for attrition. At each timepoint, past month alcohol use frequency was self-reported, parents and cohort members reported internalizing/externalizing symptoms using the Strengths and Difficulties Questionnaire. We controlled for alcohol expectancies, sex, and four cumulative risk indices (perinatal risk, early childhood adverse parenting, longitudinal parent-level risk occurrence, and persistent household socioeconomic deprivation). More frequent past month alcohol use at age 11 predicted increased internalizing symptoms at age 14 (β = 0.06; p =.01). More frequent past month alcohol use at age 14 predicted increased externalizing symptoms at age 17 (β = 0.11; p <.001). Increased internalizing symptoms consistently predicted reduced alcohol use at the next timepoint throughout the study period (11 years: β= -0.04; p =.03; 14 years: β= -0.09; p <.001). Increased externalizing symptoms at age 11 predicted increased alcohol consumption at age 14 (β = 0.06; p =.004). Frequent adolescent alcohol consumption represents a significant risk for subsequent mental health difficulties. Externalizing symptoms and alcohol use frequency appear to exacerbate one another. Internalizing symptoms may reduce the risk of frequent alcohol consumption. Incorporating routine alcohol screening into adolescent mental health treatment settings could reduce the risk of comorbid externalizing and alcohol use disorders.

Sleep has been found to be essential to physical and mental health. Sexual and gender minority (SGM; e.g., lesbian, gay, bisexual, transgender, nonbinary) individuals experience significant health disparities, and emerging research indicates that this includes disparities in sleep health. However, the current literature on sleep health in this population has not previously been rigorously reviewed. This scoping review provides a comprehensive overview and synthesis of the current literature on SGM sleep health in the United States. Following established scoping review methodology, we systematically searched PubMed, CINAHL, PsycINFO, LGBTQ + Source, and Scopus; 76 studies met inclusion criteria. Included studies indicated significant sleep disparities exist for SGM people, particularly sexual minority women and gender minority people. Social determinants of health, including bullying and discrimination, were associated with worse sleep health. Included studies were heterogeneous and had methodological weaknesses, leaving opportunities for future research. Overall, findings point to the need for more rigorous research to advance understanding of sleep health across SGM subgroups and inform interventions to improve sleep health among SGM people, given the known negative impact of poor sleep on overall health.

Part I of this systematic review summarized the state-of-the-art of pediatric psychopharmacology for Autism Spectrum Disorder (ASD), a severe and lifelong neurodevelopmental disorder. The purpose of this Part II follow-up article is to provide a systematic overview of the experimental psychopharmacology of ASD. To this aim, we have first identified in the Clinicaltrials.gov website all the 157 pharmacological and nutraceutical compounds which have been experimentally tested in children and adolescents with ASD using the randomized placebo-controlled trial (RCT) design. After excluding 24 drugs already presented in Part I, a systematic review spanning each of the remaining 133 compounds was registered on Prospero (ID: CRD42023476555), performed on PubMed (August 8, 2024), and completed with EBSCO, PsycINFO (psychology and psychiatry literature) and the Cochrane Database of Systematic reviews, yielding a total of 115 published RCTs, including 57 trials for 23 pharmacological compounds and 48 trials for 17 nutraceuticals/supplements. Melatonin and oxytocin were not included, because recent systematic reviews have been already published for both these compounds. RCTs of drugs with the strongest foundation in preclinical research, namely arbaclofen, balovaptan and bumetanide have all failed to reach their primary end-points, although efforts to target specific patient subgroups do warrant further investigation. For the vast majority of compounds, including cannabidiol, vasopressin, and probiotics, insufficient evidence of efficacy and safety is available. However, a small subset of compounds, including N-acetylcysteine, folinic acid, l-carnitine, coenzyme Q10, sulforaphane, and metformin may already be considered, with due caution, for clinical use, because there is promising evidence of efficacy and a high safety profile. For several other compounds, such as secretin, efficacy can be confidently excluded, and/or the data discourage undertaking new RCTs. Part I and Part II summarize "drug-based" information, which will be ultimately merged to provide clinicians with a "symptom-based" consensus statement in a conclusive Part III, with the overarching aim to foster evidence-based clinical practices and to organize new strategies for future clinical trials.

PURPOSE/OBJECTIVE:Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems. METHODS: Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.5-18 years by surveys. We examined mean differences in CBCL Total Problems and DSM-oriented subscale scores by autism diagnosis and by child sex. Analyses using logistic regression were conducted to examine whether autism was associated with higher CBCL scores. We further examined if these relationships differed by child age category (< 6 years, 6-11 years, 12 + years). The relationships between SRS score and CBCL total and subscale scores were examined using quantile regression models, with analyses adjusted for child sex and age. RESULTS: In ECHO, 553 youth were reported by a parent to have a clinician diagnosis of autism spectrum disorder (ASD) (432 [78%] boys and 121 [22%] girls). Youth on the spectrum had higher mean CBCL raw scores on Total Problems and all DSM-oriented subscales compared to those not on the spectrum (all p < 0.0001). Analyses adjusted for sex and stratified by age group indicated that higher odds of autism diagnosis were associated with total, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scales in the top 30% of the CBCL score distribution. Autistic girls were more likely to have parent-reported depression and anxiety compared to autistic boys. In quantile regression analyses, we observed evidence of stronger associations between SRS and CBCL for those in higher quantiles of CBCL total problems scale score (beta representing 1-unit change in SRS associated with 1-unit increase in CBCL total problems scale score), among children in the 70-90th percentile (β = 1.60, p < 0.01), or top 10th percentile (β = 2.43, p < 0.01) of the CBCL total problems scale score distribution. Similar findings were seen for the DSM-oriented depression, anxiety, and ADHD subscales. CONCLUSION/CONCLUSIONS: Results from this large national sample suggest increased behavioral and emotional problems among autistic children compared to non-autistic children throughout early life. Among children on the spectrum this may warrant increased monitoring for co-occurring behavioral and emotional problems.

Individual differences in how the brain responds to novelty are present from infancy. A common method of studying novelty processing is through event-related potentials (ERPs). While ERPs possess millisecond precision, spatial resolution remains poor, especially in infancy. This study aimed to balance spatial and temporal precision by combining ERP data with functional magnetic resonance imaging (fMRI) data. Twenty-nine infants (15 female) underwent resting-state fMRI (M

BACKGROUND:Children's social-emotional development and mental well-being are critical to adult mental health. However, little is known about the mechanisms or factors that contribute to poor child mental health in low- and middle-income countries. Given the lack of child mental health research to guide interventions or social-emotional learning programs and policy planning, the present study aimed to address these knowledge gaps by examining the psychopathology mechanism involved in the development of childhood mental health problems. METHODS:This cross-sectional study recruited parents (N = 393) whose children attended preschool to primary classes in the Arghakhanchi district of Nepal. Data were gathered through parent interviews. Structural Equation Modeling was used to examine the pathways of the mediational mechanism that examined the influence of parental well-being on parenting and children's mental health outcomes. RESULTS:Approximately 22% of the parents were at risk for moderate to severe mental health problems (anxiety: 24%, depression:19%). Parental mental health problems were higher in families who reported food insecurity, among female parents, less educated parents, and those who perceived themselves on a lower social ladder. Parental mental health, social support, and perceived class were associated with parent-child conflict. Greater parent-child conflict was associated with decreased social competence and increased anger, anxiety, and depression in children. CONCLUSION/CONCLUSIONS:The results partially support the mediational model that Nepali parents' well-being (especially in mental health symptoms, social support, and perception of family's social class domains) is associated with less optimal parenting and, in turn, greater child mental health problems and lower social competence. This study provides new evidence of cross-cultural consistency in child psychopathology and guides the development of evidence-based programs to prevent and promote mental health among Nepali children and families.