Faculty Bibliography

Children presenting comorbid attention-deficit/hyperactivity disorder (ADHD) and depression symptoms have higher risks of later suicidal ideation and attempt. However, it is unclear to what extent this risk stems from individual differences in the genetic predisposition for ADHD and/or depression. We investigated the unique and combined contribution of genetic predisposition to ADHD and depression to suicidal ideation and attempt by early adulthood. Data were from two longitudinal population-based birth cohorts, the Quebec Longitudinal Study of Child Development and the Quebec Newborn Twin Study (total N = 1207). Genetic predisposition for ADHD and depression were measured using polygenic scores. Suicidal ideation and attempt by age 20 years were self-reported via questionnaires. Across the two cohorts, suicidal ideation and attempt were reported by 99 (8.2%) and 75 (6.1%) individuals, respectively. A higher polygenic score for depression was associated with significantly higher risk of suicidal ideation and attempt, while no significant associations were found for ADHD polygenic score. However, we found an interaction between polygenic scores for depression and ADHD in the association with suicide attempt (P = 0.012), but not suicidal ideation (P = 0.897). The association between polygenic score for depression and suicide attempt was significantly stronger for individuals with a higher polygenic score for ADHD. Individuals scoring ≥ 1-SD above the mean for both polygenic scores were at increased risk for suicide attempt compared to individuals with lower scores (OR 4.03, CI 1.64-9.90), as well as compared to individuals scoring ≥ 1-SD above the mean in only depression (OR 2.92, CI 1.01-8.50) or only ADHD (OR 4.88, CI 1.56-15.26) polygenic scores. Our findings suggest that genetic predisposition for ADHD and depression contributes to increase the risk of suicide attempt in a multiplicative, rather that additive, way. Our results contribute to our understanding of the etiology of suicide risk and may inform screening and risk stratification.

Chronic motor or vocal tic disorder (CMVTD) is a distressing neuropsychiatric condition. A subset of patients remains refractory to currently approved therapies. The present report describes a pediatric patient with CMVTD who had previously failed multiple pharmacological treatments, including two Food and Drug Administration (FDA)-approved agents (pimozide, aripiprazole), guanfacine, psychotherapy, and novel compounds (lumateperone, cariprazine). The patient was initiated on valbenazine, titrated to 80 mg daily. Clinical improvement was noted within 24-48 hours, with sustained benefit and good tolerability. Tic severity, measured by the Yale Global Tic Severity Scale-Revised (YGTSS-R), improved from 65 at baseline to five following treatment (net reduction of 60 points). This case illustrates a marked therapeutic response to valbenazine in a patient with CMVTD refractory to conventional and novel therapies. These observations highlight the potential role of vesicular monoamine transporter 2 (VMAT2) inhibition in tic disorders and also the need for further clinical study.

The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HR_adjusted 0.95, 95% CI 0.82-1.11), ADHD (HR_adjusted 0.92, 95% CI 0.78-1.08), or ASD (HR_adjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.

PURPOSE/OBJECTIVE:To estimate the prevalence and geographic variation of serious mental illness (SMI) among young adults enrolled in Medicaid and to identify individual and community-level factors associated with SMI. METHODS:We used New York Medicaid data for over 1.6 million young adults aged 18-34 years with continuous Medicaid enrollment from April 2021 through March 2022. We merged 3 additional county and zip code-level datasets, including the Distressed Communities Index, Area Health Resource File, and New York homelessness data. We used descriptive analyses, data visualization methods, and multivariable logistic regression to estimate the prevalence of SMI and identify individual- (sex, race and ethnicity, age, disability aid, and homelessness) and community-level (geography, community distress, number of hospital beds, and community mental health centers per capita) factors associated with SMI. RESULTS:The 12-month prevalence of SMI was 8.3% in New York State, with wide geographic variation by zip codes, ranging from 0% to 39%. Young adults identifying as Asian, Black, and Latinx (compared to White), and those living in zip codes with the most community distress were associated with lower odds of SMI, odds ratios (OR) ranged from 0.47 (Asian) (95% confidence interval [CI] [0.46-0.49]) to 0.95 (Latinx) (CI [0.93-0.97]). Young adults identifying as female (compared to male), receiving disability, experiencing homelessness, and rural residence were associated with higher odds of SMI, ORs ranged from 1.64 (female) (95% CI [1.62-1.66]) to 5.49 (homelessness) (95% CI [5.33-5.66]). DISCUSSION/CONCLUSIONS:SMI prevalence varies by individual- and community-level factors, including homelessness and rural residence, signaling the need for specific interventions and policies.

The subgenual anterior cingulate cortex (sgACC) plays a central role in the pathophysiology of major depressive disorder (MDD). Its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) is associated with transcranial magnetic stimulation (TMS) treatment outcomes. Previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power. Furthermore, calculating sgACC-FC to target TMS individually is challenging. We used a large multi-site cross-sectional sample (1660 patients with MDD vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT) to systematically delineate case-control difference maps of sgACC-FC. We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy. Next, we developed an MDD big data-guided, individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets. We found enhanced sgACC-DLPFC FC in patients with MDD compared with healthy controls (HC). These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC. We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples. This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets. We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large, independently ascertained sample and demonstrated the potential impact of such case-control differences on FC-guided localization of TMS targets.

Dialectical thinking represents a cognitive style emphasizing change, contradiction, and holism. Cross-cultural studies reveal a stark contrast of dialectical thinking between East Asian and Western cultures, highlighting East Asians' superior ability to embrace contradictions and foresee transformation, fostering psychological resilience through emotional complexity and tolerance for contradictions. Despite its importance, the neural basis of dialectical thinking remains underexplored. This review synthesizes current neuroscientific findings and introduces the dialectical-integration network (DIN) hypothesis, which identifies key brain regions such as the dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), dorsal lateral prefrontal cortex (DLPFC), nucleus accumbens, basal ganglia, and amygdala. These regions, along with networks like the default mode network (DMN) and frontoparietal network (FPN), facilitate holistic reasoning, conflict resolution, and sensory-emotional integration. The psychological benefits of dialectical thinking include enhanced cognitive flexibility, reduced emotional extremes, and improved conflict resolution. This review emphasizes the need for cross-cultural and neuroscientific research to explore the principle of change, a core aspect of dialectical cognition. By bridging cultural psychology and cognitive neuroscience, this work offers theoretical and methodological insights into culturally shaped cognitive styles, with practical applications in education, mental health, and intercultural communication. The DIN model provides a framework for future research on dynamic neural interactions supporting dialectical thinking.

OBJECTIVE:To examine the effects of drug treatment for attention deficit/hyperactivity disorder (ADHD) on suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. DESIGN/METHODS:Emulation of target trials. SETTING/METHODS:Linkage of national registers in Sweden, 2007-20. PARTICIPANTS/METHODS:People aged 6-64 years with a new diagnosis of ADHD, who either started or did not start drug treatment for ADHD within three months of diagnosis. MAIN OUTCOME MEASURES/METHODS:First and recurrent events of five outcomes over two years after ADHD diagnosis: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. RESULTS:90.1 per 1000 person years; incidence rate ratio 0.98, 0.96 to 1.01). The reduced rates were more pronounced among individuals with previous events, with incidence rate ratios ranging from 0.79 (0.72 to 0.86) for suicidal behaviours to 0.97 (0.93 to 1.00) for accidental injuries. For recurrent events, drug treatment for ADHD was significantly associated with reduced rates of all five outcomes, with incidence rate ratios of 0.85 (0.77 to 0.93) for suicidal behaviours, 0.75 (0.72 to 0.78) for substance misuse, 0.96 (0.92 to 0.99) for accidental injuries, 0.84 (0.76 to 0.91) for transport accidents, and 0.75 (0.71 to 0.79) for criminality. CONCLUSIONS:Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes. This target trial emulation study using national register data provides evidence that is representative of patients in routine clinical settings.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Unaccompanied migrant youths often confront traumatic experiences elevating their risk for mental health symptoms. However, United States-based research on mental health services for this population, particularly Indigenous youths, is limited. Objectives were to examine mental health screening and referral, characteristics associated with referrals, and clinical rationale for screening result/referral discordance. METHODS:All unaccompanied migrant youths with pediatric intake visits at a healthcare-legal clinic between 3/2020-2/2023 were included (N=100). Retrospective cohort data were extracted from medical chart and program registry, including pediatricians' rationale for referrals. Chi-square and t-tests were used to compare rates of screening, evaluation, and discordant referrals by sociodemographic characteristics. Logistic regression was used to identify associations with mental health referral. Exploratory analyses examined referrals by Indigenous group. RESULTS:Youths had a mean (SD) age of 17.5 (2.5) years, most were assigned male at birth (66 [66%]), from Central America (83 [83%]), and one-third were Indigenous. Odds of mental health referral were higher for youths who were assigned female at birth (adjusted OR, 3.00 [95% confidence interval, 1.13-7.87), non-Indigenous (adjusted OR, 2.73; 95% confidence interval, 1.01-7.40), and reported more trauma types (adjusted OR, 1.38; 95% confidence interval, 1.02-1.87). One-third of referrals were for trauma or mental health symptoms identified by pediatricians, but not screeners. CONCLUSION/CONCLUSIONS:Most unaccompanied migrant youths had mental health referrals, one-third of which were for mental health symptoms undetected by screeners at pediatric visit. Findings highlight sociodemographic differences in mental health referrals, with non-Indigenous and female youths having higher odds of referral.

While prior research has explored the neurobiological mechanisms underlying adolescent school performance, these mechanisms remain poorly understood in college students. Impulsivity has been highlighted as a key factor affecting academic success; however, its influence on the relationship between school performance and brain structure remains underexplored. In this study, we used a sample of college students to investigate which gray matter volume (GMV) in brain regions was associated with grade point average (GPA), and whether impulsivity mediates these relationships. Our findings revealed correlations between GMV in the caudate nucleus (CN) and cerebellum with GPA. Increased CN was correlated with poorer GPA through higher impulsivity, whereas higher cerebellum was associated with better GPA through lower impulsivity. These results indicate that CN and cerebellum play crucial roles in school performance and associated impulsivity. Various interventions targeting impulsivity, such as therapy, counseling, and medication, could improve educational outcomes by addressing the underlying neurobiological factors.