Faculty Bibliography

IMPORTANCE/UNASSIGNED:Adult attention-deficit/hyperactivity disorder (ADHD) diagnoses are rising, yet distinctions between those diagnosed in childhood or adolescence vs adulthood remain underexplored. OBJECTIVES/UNASSIGNED:To characterize differences in demographic, clinical, and genetic profiles between adults with ADHD diagnosed in childhood or adolescence (youth-diagnosed) vs adulthood (adult-diagnosed), and to compare the profile of each group with that from matched individuals without ADHD. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional, multicenter study used data collected in the All of Us Research Program, a nationwide US cohort integrating clinical and genetic data, from June 2017 to September 2023. Analyses were performed between July and December 2025. Participants were adults who self-reported an ADHD diagnosis, dichotomized by age at first diagnosis into youth-diagnosed (0-17 years) and adult-diagnosed (≥18 years) ADHD groups. Each ADHD group was independently matched 1:2 via propensity scores to controls without ADHD on age, sex, race and ethnicity, educational attainment, and income. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcomes were self-reported psychiatric or somatic co-occurring conditions, measures of functional impairment (general health and daily functioning), and ADHD polygenic risk scores. RESULTS/UNASSIGNED:Of 13 527 adults with ADHD, 3853 (28.5%; mean [SD] age, 34.8 [11.5] years; 71.5% female) were youth-diagnosed and 9674 (71.5%; mean [SD] age, 43.8 [14.3] years; 75.3% female) adult-diagnosed. Adult-diagnosed individuals were older and had higher educational attainment (eg, 548 [14.2%] vs 2690 [27.8%] for advanced degree) and annual household income (eg, 364 [9.4%] vs 1407 [14.5%] for $100 001-$150 000). Adjusting for age and sex, adult- versus youth-diagnosed ADHD was associated with lower adjusted probabilities of most psychiatric comorbidities (8 of 9 conditions) with the largest absolute differences for posttraumatic stress disorder (-7.50 [95% CI, -9.25 to -5.88] percentage points [pp]), bipolar disorder (-7.44 [95% CI, -8.99 to -6.00] pp), and personality disorder (-4.78 [95% CI, -5.89 to -3.81] pp). For somatic conditions (6 of 9 categories), the largest absolute differences were for lung conditions (-7.88 [95% CI, -9.73 to -5.79] pp), digestive conditions (-7.27 [95% CI, -9.12 to -5.28] pp), and bone, joint, and muscle conditions (-7.00 [95% CI, -8.78 to -5.20] pp). For impairment in overall health and daily functioning (7 of 9 measures), the largest absolute differences were for physical health (-3.63 [95% CI, -4.83 to -2.44] pp), being bothered by emotional problems in the past 7 days (-2.51 [95% CI, -3.79 to -1.24] pp), and general health (-2.26 [95% CI, -3.40 to -1.18] pp). Compared with their matched controls without ADHD, both ADHD groups showed markedly higher probability differences of comorbid psychiatric (eg, for depression, 39.33 [95% CI, 38.19-40.48] pp for adult-diagnosed ADHD and 36.92 [95% CI, 35.05-38.83] pp for youth-diagnosed ADHD) and somatic (eg, for brain and nervous system conditions, 21.86 [95% CI, 20.64-22.93] pp for adult-diagnosed ADHD and 22.84 [95% CI, 21.05-24.83] pp for youth-diagnosed ADHD) conditions, and functional impairments (eg, for bothered by emotional problems past 7 days, 6.11 [95% CI, 5.45-6.80] pp for adult-diagnosed ADHD and 7.29 [95% CI, 5.99-8.60] pp for youth-diagnosed ADHD). ADHD polygenic risk scores were lower in adult- vs youth-diagnosed groups (Cohen d, -0.17 [95% CI, -0.21 to -0.12]) and higher in youth-diagnosed (Cohen d, 0.21 [95% CI, 0.16-0.26]) and adult-diagnosed (Cohen d, 0.12 [95% CI, 0.09-0.15]) groups compared with controls. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study of adults with ADHD, individuals first diagnosed with ADHD in adulthood showed a milder ADHD-like clinical and genetic profile than those diagnosed in childhood or adolescence, which may contribute to later recognition of the disorder. Nonetheless, adults diagnosed either as youths or adults exhibited profiles characteristic of ADHD relative to matched controls without ADHD, including substantial burden, supporting adult-diagnosed ADHD as a clinically important subgroup warranting recognition and management.

Family-based interventions have been shown to improve behavioral and justice-related outcomes for youth. There has been less focus on whether family-based interventions are effective at reducing youth recidivism, especially for newer or lesser known interventions. To address this gap, we conducted a systematic review of studies utilizing family-based interventions to address recidivism for youth involved in the juvenile justice system. Of the identified 3,497 unique articles, 235 full-text articles were reviewed and 31 met criteria for inclusion in the review. A variety of family-based interventions were used, including both widely known (e.g., multisystemic therapy) and lesser known interventions. Most studies demonstrated significant reductions in recidivism, with some mixed findings depending on the type of charge, assessment timepoint, measure of recidivism, or moderating factors. The findings from this review corroborate prior research on the effectiveness of well known interventions for reducing recidivism and highlight the promise of newer interventions. The results also highlight the need for additional research in this area, as well as a greater focus on better understanding the moderating factors that may affect treatment outcomes.

Study DesignRetrospective cohort study.ObjectivesTo characterize longitudinal durability of cervical deformity (CD) correction, identify predictors of alignment failure, and define failure mechanism timing across the first postoperative year.Methodsof 155 operative CD patients in a prospectively maintained multicenter database, 89 had complete four-timepoint radiographic follow-up. Well-alignment was defined as cSVA <4 cm. Patients were grouped as A (maintained), B (corrected then deteriorated), or C (never aligned). Analyses included Cox regression (n=47, 17 events), Kaplan-Meier with restricted mean survival time (RMST), and mixed-effects logistic regression across four timepoints (n=356; ICC=0.36). Concurrent thoracolumbar deformity was excluded.ResultsWell-aligned proportion fell from 48.3% at 3 months to 33.7% at 1 year (A=34%, B=19%, C=47%). DJK was most strongly associated with alignment loss (HR 5.21, 95% CI 1.94-13.98; OR 0.09), with alignment maintained 4.1 versus 9.8 months (RMST difference 5.7, p=0.001). Lower postoperative cSVA paradoxically increased failure hazard (HR 0.58/10 mm, p=0.002). Older patients deteriorated faster (Time×Age OR 0.88, p=0.022). Failure mechanisms shifted from DJK at 3 months (50%) to PJK at 6 months (75%) to global compensation loss at 1 year (71%). No surgical parameters differed between groups.ConclusionsFewer than one-third of patients maintain alignment at 1 year. DJK, advanced age, and lower postoperative cSVA were most strongly associated with failure (17 events; limited precision). Mechanisms appeared to shift from junctional failure early to global decompensation late. Alignment loss was not accompanied by significant 1-year NDI or EQ-5D differences, framing radiographic deterioration as an early surveillance marker rather than clinical failure. Individualized risk stratification and surveillance are supported.

IMPORTANCE:Although fluoride exposure at high levels during the perinatal period has been associated with socioemotional problems among children, there is limited evidence regarding potential associations at lower levels of fluoride exposure, particularly in the US. OBJECTIVE:To examine the association between prenatal exposure to public drinking water fluoride levels and children's socioemotional problems in a pooled US pediatric consortium. DESIGN, SETTING, AND PARTICIPANTS:This cohort study used observational pregnancy cohort data from January 1, 2005, to December 31, 2019, on children aged 1.5 to 17 years from the Environmental Influences on Child Health Outcomes (ECHO) Cohort, which took place at 20 prenatal pediatric cohort sites across 34 US states. Statistical analysis was conducted from December 2024 to December 2025. EXPOSURE:Area-level, time-weighted, mean fluoride concentrations in public water were estimated based on residential addresses during pregnancy. MAIN OUTCOMES AND MEASURES:Children's socioemotional problems were assessed using caregiver reports of internalizing and externalizing problems via the Child Behavior Checklist. Generalized estimating equation models evaluated the adjusted mean difference in T scores (1) across the range of exposure values in cubic spline models, (2) per 500.0-µg/L higher fluoride level in linear models, (3) across quartiles of exposure, and (4) at the US Public Health Services recommended cutoff (≤700.0 µg/L; 3998 less than the cutoff). RESULTS:The cohort comprised 5520 children (mean [SD] age, 5.8 [3.0] years; 2849 boys [51.6%]). The mean (SD) prenatal time-weighted water fluoride level was 407.9 (361.0) µg/L (range, <1.4-3272.5 µg/L). The adjusted mean difference in emotional and behavioral problem T scores per 500.0-μg/L higher exposure to prenatal public water fluoride was -0.15 (95% CI, -0.85 to 0.56) for internalizing problems and 0.06 (95% CI, -0.44 to 0.55) for externalizing problems, consistently showing no associations at the continuous level. However, some positive associations were observed only when using change point models for externalizing problems (adjusted mean difference, 1.59 [95% CI, 0.72-2.47] per 500.0-µg/L increase above the inflection point), and for some subgroups. CONCLUSIONS AND RELEVANCE:In this cohort study, prenatal exposure to fluoride levels in regulated public water was not associated with internalizing and externalizing problems among offspring. In change point models, positive associations were found for externalizing problems. The results contribute to growing evidence that could inform future policy decisions regarding fluoride in the US public water systems. Additional studies are needed to further investigate this association, especially examining other sources of fluoride that may have an association with children's emotional and behavioral problems.

Tobacco products, consisting of the highly addictive chemical, nicotine, are commonly used in the United States. Chronic nicotine use remains the leading cause of preventable disease and death in the United States. The vast majority of adults with nicotine addiction began using the substance during adolescence. Existing research suggests that adolescents experience increased susceptibility to nicotine addiction. Nicotine addiction or tobacco use disorder is characterized by clinically significant impairment and distress related to nicotine consumption (DSM-5). Individuals must have at least 2 of 11 symptoms during a 12 month period in order to meet diagnostic criteria.

ObjectiveThe prevalence of attention-deficit/hyperactivity disorder (ADHD) has risen in recent decades. The objective of this study was to identify trends in prevalence rates of ADHD medication use as well as any patterns of ADHD medication use among individuals aged up to 24 years in Quebec, Canada.MethodWe conducted a repeated cross-sectional study using medico-administrative data between the fiscal years 2000 to 2001 and 2022 to 2023. We estimated crude and age-adjusted prevalence rates along with their 99% confidence intervals according to sex, age (only for crude estimates), material and social deprivation, and ADHD medication type, namely stimulants (amphetamine-based and methylphenidate-based medications) and non stimulants (atomoxetine and guanfacine). We also analyzed prescribing by prescriber type.ResultsAmong the 4,771,183 individuals aged ≤24 years, 7.7% claimed ADHD medications. Age-adjusted prevalence of ADHD medication use increased from 2000 to 2001 (1.9%) until 2017 to 2018 (7.9%) and plateaued afterwards. The analysis highlighted not only variations in medication use over time but also by sex, with males more likely to be prescribed these medications than females. Family physicians have become the primary prescribers, overtaking pediatricians in recent years. Stimulant medications were the most common treatment throughout the study period, though we observed diversification in prescribed ADHD medication types across age groups.ConclusionsThis study emphasizes a significant increase in ADHD medication use from 2000 to 2018 and a stabilization in use afterwards. The expansion of diagnostic criteria in 2013 and heightened awareness may have narrowed the disparity between the condition's prevalence and its management and may explain the increase in use observed in earlier years and the stabilization observed over the more recent years. The disparities between males and females, as well as between age groups, highlight the need for continuous monitoring of prescribing trends and support targeted equity evaluations to inform service planning and improve access where needed.

PURPOSE/OBJECTIVE:performed with autistic youth with varying presentations. METHODS:administration and results were analyzed and compared across relevant clinical characteristics, including age, language level, and autism severity. RESULTS:results were highly correlated with existing measures, parent-child agreement was relatively low and variable across subgroups of autistic youth. CONCLUSIONS:adaptations are likely necessary to improve accessibility, linguistic clarity, and diagnostic specificity and will be important to promote scalable, equitable MH screening for autistic youth.

PURPOSE/OBJECTIVE:Effective immunotherapy for mismatch repair proficient colorectal cancer (CRC) is lacking. We examined the safety and efficacy of the novel next-generation immune activator/Fc-enhanced CTLA-4 inhibitor botensilimab (BOT) plus PD-1 inhibitor balstilimab (BAL) in the neoadjuvant setting for patients with resectable CRC. PATIENTS AND METHODS/METHODS:Patients 18 years of age or older with non-metastatic CRC awaiting surgical resection were eligible. BOT/BAL was administered followed by surgical resection. In cohort A, patients received BOT 75 mg d1 and BAL 240 mg d1, 15; in cohorts B/C, patients received 2 additional BAL doses (d29, 43). The primary study objectives were safety, feasibility (based on surgery delay), and pathologic response. Exploratory analyses examined changes in the tumor microenvironment. RESULTS:Twenty-four eligible patients (26 tumors, n=22 pMMR; n=4 dMMR) were enrolled (two patients had synchronous primary tumors). Neoadjuvant BOT/BAL was safe and did not delay planned surgery in any patient. The major pathologic response rate was 41% (95% CI, 21%-64%) for pMMR, and 100% (95% CI, 40%-100%) for dMMR CRC. BOT/BAL was associated with significant anti-tumor effects in the tumor microenvironment, with an increase in the density and proportion of CD8+ T cells, a reduction in tumor infiltrating FOXP3+ Tregs, and evidence of increased immune cell-cell interaction in responding patients. CONCLUSIONS:These findings demonstrate safety, feasibility, and encouraging pathological responses for BOT/BAL in both non-metastatic pMMR and dMMR CRC. Tumor microenvironment remodeling suggests a robust anti-tumor immune response induced by immunotherapy. These data support the continued development of BOT/BAL in CRC.

BACKGROUND:Autism is most often diagnosed after the age of 3, despite evidence that neurodevelopmental differences emerge within the first 2 years of life and that genetic and familial risk can be identified at birth. METHODS:Established in September 2022 (anticipated duration of 5-7 years), the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center is an ongoing longitudinal cohort study designed to characterize early developmental trajectories associated with autism and evaluate the impact of providing genetic information to families. RESULTS:Infants who undergo genomic newborn screening and enroll in PROGRESS are followed from 3 to 24 months of age and categorized into three groups: identified genetic probability (IGP), familial likelihood without identified genetic probability (Baby Siblings), and no identified genetic probability (NGP). Assessments include electroencephalography, electrocardiography, auditory, eye tracking, developmental testing, caregiver-infant interaction, and caregiver-reported measures. Autism screening is conducted at 18 months, with comprehensive diagnostic evaluation at 24 months. Caregiver psychosocial experiences of receiving early genetic information are assessed through surveys and interviews. CONCLUSION/CONCLUSIONS:By integrating genomic probability with early neurobehavioral development and family experiences, PROGRESS provides a framework to inform ethical genomic screening, developmental monitoring, and timely access to early intervention supported by a family navigator. IMPACT/CONCLUSIONS:This study presents the rationale and methods of the ongoing Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University, which began in September 2022 (anticipated duration of 5-7 years). PROGRESS is a prospective longitudinal cohort assessing infants with identified genetic probability, familial likelihood, or no identified genetic probability for autism from 3 to 24 months of age. By linking early genetic probability with brain-behavioral trajectories, PROGRESS advances understanding of autism-related differences before clinical diagnosis and provides an empirically grounded foundation for ethical genomic newborn screening and optimized early developmental monitoring and intervention.