Faculty Bibliography

BACKGROUND/UNASSIGNED:Adolescence is a period of heightened risk for psychopathology. Recent studies suggest shared neural correlates across psychiatric disorders in brain networks involved in emotional and cognitive processes. However, the visual network-crucial for extracting and processing emotional information-has received less attention. Here, using a transdiagnostic approach, we focus on the visual network to investigate how youth with psychopathology represent and differentiate between emotional face categories during a cognitively demanding task, for which emotional content is irrelevant. METHODS/UNASSIGNED:= 4952 after quality control). Symptoms of psychopathology were based on the Child Behavior Checklist. Participants performed an emotional n-back task in the scanner. Representational similarity analysis was performed to examine dissimilarities in neural representations between emotional categories in functional brain networks. RESULTS/UNASSIGNED:< .001), and predicted symptoms a year later. CONCLUSIONS/UNASSIGNED:Using a transdiagnostic approach, we showed that the distinctiveness in neural representations of task-irrelevant emotional information in the visual cortex is positively correlated with psychopathology. Together, our findings suggest the importance of the visual network and early visual areas in understanding neural mechanisms of emotional processing in youth with psychopathology.

Identifying updated, evidence-based risk and protective factors for psychotic disorders is essential to advancing scientific and clinical knowledge of their etiology. Since the most recent umbrella review published in this journal, the evidence base has expanded substantially. Following a pre-registered protocol, we searched the Web of Science for systematic reviews with meta-analyses of observational studies published between the search date of the last umbrella review (February 1, 2017) and March 31, 2025, examining associations of sociodemographic, parental, perinatal, and later factors or antecedents with ICD/DSM (any version) diagnoses of non-organic psychotic disorders. We graded associations between each putative factor and psychotic disorders using standardized international classification criteria: convincing (class I), highly suggestive (class II), suggestive (class III), and weak (class IV). We also conducted sensitivity analyses: a) lowering the classification criterion requiring more than 1,000 cases to 500 cases, b) restricted to prospective studies (class I-II factors), and c) testing more robust estimates of uncertainty (Hartung-Knapp-Sidik-Jonkman method). Then, we estimated the population attributable fraction (PAF) for potentially modifiable class I-III factors. Study quality was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR). A total of 69 systematic reviews and meta-analyses were included, reporting on 970 individual studies and 221 risk or protective factors for psychotic disorders. Six risk factors showed convincing (class I) evidence of association: Black-African ethnicity in England (odds ratio, OR=4.89, 95% CI: 4.04-5.92), South Asian ethnicity in England (OR=2.15, 95% CI: 1.69-2.73), paternal age <20 years (OR=1.34, 95% CI: 1.20-1.50), birthweight under 2,000 g (OR=1.77, 95% CI: 1.48-2.13), birthweight under 2,500 g (OR=1.50, 95% CI: 1.38-1.64), and maternal history of three or more previous pregnancies (OR=1.32, 95% CI: 1.20-1.45). Eighteen additional factors were highly suggestive (class II): maternal psychosis, Black-Caribbean ethnicity in England, any maternal mental health disorder, ethnic minority status in a low ethnic density area, first-generation immigrant status, cannabis use 5 to 7 days per week, Toxoplasma gondii IgG positivity, history of attention-deficit/hyperactivity disorder (ADHD), trait anhedonia, olfactory identification ability, premorbid IQ, and seven factors pertaining to minor physical anomalies. Two additional factors were upgraded from class IV to class II in our sensitivity analyses: clinical high-risk for psychosis (CHR-P) state, and soft neurological signs. Twenty-six factors (including four protective factors) were suggestive (class III), 75 were weak (class IV), and 96 were non-significant. Sensitivity analyses restricted to prospective studies downgraded some of the above factors, but only total minor physical anomalies became non-significant. The largest PAFs (>10%) were found for childhood adversities (40.69%), Toxoplasma gondii IgG positivity (20.47%), cannabis use 5-7 days per week (12.75%), and CHR-P state (12.68%). The sensitivity analyses employing robust uncertainty estimates confirmed that, among class I factors, Black-African ethnicity in England, birthweight under 2,000 g, and birthweight under 2,500 g retained their level of evidence. The mean AMSTAR score was 7.73 (SD=2.09). These findings provide an evidence-based, updated atlas of risk and protective factors for psychosis, advancing epidemiological knowledge, refining precision psychiatry, identifying targets for preventive intervention, and guiding global public health research.

IMPORTANCE/UNASSIGNED:The terms neurodivergence and neurodiversity are increasingly used across mental health and broader clinical literature, as well as in clinical practice, clinical service commissioning, and policy contexts, despite their lack of clinical and diagnostic specificity. OBJECTIVE/UNASSIGNED:To quantitively map clinical diagnoses associated with the terms neurodivergence and neurodiversity in the empirical mental health literature through a scoping review conducted with experts with lived experience . EVIDENCE REVIEW/UNASSIGNED:Following JBI methods and the PRISMA extension for scoping reviews, PubMed/Medline, Web of Science, Embase, and PsycINFO were searched up to August 1, 2025, and identified 134 studies including 151 134 participants that recruited participants defined as neurodivergent or neurodiverse. FINDINGS/UNASSIGNED:Participants were primarily identified through self-reported diagnoses (n = 56 [41.8%]) or self-identification (n = 50 [37.3%]). A heterogeneous range of diagnoses was associated with neurodivergence and neurodiversity, most commonly autism (n = 92 [68.7%]), followed by ADHD (n = 86 [64.2%]), dyslexia (n = 44 [32.8%]), dyspraxia (n = 21 [15.7%]), anxiety disorder (n = 20 [14.9%]), and dyscalculia (n = 17 [12.7%]). Notably, 29 studies (21.6%) did not specify any clinical diagnoses. CONCLUSIONS AND RELEVANCE/UNASSIGNED:While neurodivergence and neurodiversity are valuable for capturing lived experience, their lack of specificity may introduce substantial heterogeneity in research focused on clinical categories. These findings suggest prioritizing precise diagnostic descriptors in clinical practice and research involving clinically defined conditions, while reserving neurodivergent for studies and contexts focused on self-identification and identity.

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.

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.

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.

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: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.