Faculty Bibliography

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.

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:The maternal experience of intimate partner violence is associated with a range of emotional and behavioural problems in young children. OBJECTIVE:To prospectively examine the impact of maternal perinatal intimate partner violence experiences on children's risk trajectories of social-emotional development, including theoretically relevant social, economic, maternal mental health and trauma factors, as well as refugee status. PARTICIPANTS/METHODS:870 mother-child dyads in the WATCH mental health cohort study, half from refugee background. METHOD/METHODS:Multigroup trajectory modelling of annually collected longitudinal data at 5 timepoints, from when the children were 18-24 months to 60 months of age. RESULTS:The trajectory modelling revealed 4 distinct trajectories of child social-emotional development: (1) "none or low risk" trajectory (n = 710, 81.6 % of the sample); (2) "declining risk" trajectory (n = 66, 7.6 %); (3) "intermittent risk" trajectory (n = 64, 7.4 %); and (4) "high increasing risk" trajectory (n = 30; 3.4 %). Compared to the group 1 "none or low risk", maternal IPV exposure to physical abuse at baseline was associated with 2.45 times greater odds of children following the "intermittent risk" development trajectory, and 4.90 times greater odds of children following the "high increasing risk" trajectory. Children in trajectory 4 "high increasing risk" were more likely to be male, and mothers were more likely to be born in Australia, have no tertiary education, and experience social and economic difficulties. CONCLUSIONS:The study contributes significantly to understanding the deleterious impact of IPV on child development over time, including unique evidence that socially relevant and modifiable risk factors are more strongly associated with adverse child development than traditionally emphasised factors such as maternal mental health and child attachment factors.

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.

BACKGROUND/UNASSIGNED:Magnetic resonance imaging (MRI) and electroencephalography (EEG) are valuable tools for studying neuroanatomical and electrophysiological features of early brain development. Studies implementing neuroimaging tools in low- and middle-income countries are still rare, and there is limited data on the acceptability of such tools among rural communities. The present study explores the perceptions, feasibility, and acceptability of introducing MRI and EEG for child development research in the rural Amhara region of Ethiopia. METHODS/UNASSIGNED:= 16). A semi-structured interview included four themes: (1) Baseline imaging knowledge, (2) Perceptions of MRI and EEG, (3) Facilitators and barriers to acceptability of MRI and EEG, and (4) Recommendations to improve MRI and EEG uptake. Interviews were conducted in Amharic, the local language. All interviews were transcribed verbatim to Amharic, translated into English, and double-coded. We used thematic analysis to organize data according to predefined and emerging themes. RESULTS/UNASSIGNED:Knowledge of MRI and EEG was limited, and none of the community members had previous experiences with either technology. Broadly, participants responded positively to our introductory videos showing MRI and EEG acquisition and expressed high levels of acceptability. However, participants reported concerns about possible harms related to radiation, electrical shock, and injury from MRI/EEG procedures. Those with lesser education were identified to be less accepting of MRI/EEG. In addition, several mothers expressed that consent from their husbands was necessary for their child's participation in neurodevelopmental research. Potential logistical barriers identified included transportation challenges to the neuroimaging study sites, especially for rural-dwelling families. Creating awareness, using explanatory videos, and engaging community members and clinicians were recommended to facilitate acceptance of EEG and MRI. CONCLUSION/UNASSIGNED:In this formative study, MRI and EEG were viewed as acceptable methods for assessing child neurodevelopment in rural areas of Ethiopia. Community members' and clinicians' views were impacted largely by social, religious, educational, and logistical aspects. Concerns related to MRI radiation, electrical shock, and injuries from EEG can be addressed through awareness creation and education. Engaging community leaders and healthcare providers is key to improving acceptability.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Recent studies highlight an increase in pediatric mental health disorders, amplified by COVID-19. This study examines changes in mental health-related emergency department visits among New York City public school students across the pandemic timeline. METHODS:We employed logistic regression to examine changes in the probability of a student's emergency department visit being mental health-related, and as a secondary outcome, we analyzed the difference in same-day discharge rates between mental health-related visits and other visits. For this analysis, we used the New York City Student Population Health Registry to link public school students' records to emergency department visit data. RESULTS:No significant linear trends were observed in the average monthly probability of a mental health-related visit before March 2020. From March 2020 through June 2021 there was an increase for all groups except male elementary school students. Female middle and high school students experienced the largest increase (0.031 (CI = [0.027, 0.034])) compared to pre-pandemic (0.103 (CI = [0.103, 0.104])). Post-June 2021, all groups experienced a lower probability except for female middle and high school students, who had a 0.009 (CI = [0.007, 0.011]) higher probability than during the pandemic. Compared to the pre-pandemic period and non-mental health-related visits, a 0.043 (CI = [0.029, 0.057]) lower probability of same-day discharge was observed for mental health-related visits during the pandemic period. CONCLUSIONS:The COVID-19 pandemic correlated with a significant increase in mental health-related emergency department visits and longer stays, particularly among female middle and high school students.

INTRODUCTION/BACKGROUND:Underlying causes of Alzheimer's disease (AD) remain unknown, making it imperative to identify molecular mechanisms driving the pathobiology of AD onset and progression. METHODS:Laser capture microdissection was used to isolate layer III pyramidal neurons from post mortem human prefrontal cortex (Brodmann area 9). Single population RNA sequencing was conducted using tissue from subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. Differentially expressed genes (DEGs) were compared across groups. RESULTS:DEGs increased from prodromal (MCI vs. NCI) to progression (AD vs. MCI) to frank AD (AD vs. NCI). The majority of DEGs and pathways shared between prodromal and progression exhibited a change in the direction of dysregulation unlike pathways between progression and frank AD. DISCUSSION/CONCLUSIONS:Candidate genes and pathways were identified that demarcate early-stage AD onset from AD progression, providing a roadmap to study cortical cellular vulnerability and key targets for intervention at early stages of AD. HIGHLIGHTS/CONCLUSIONS:Pyramidal neuron differentially expressed genes (DEGs) are directionally divergent between prodromal, progression, and frank Alzheimer's disease (AD). Pyramidal neuron DEGs are directionally convergent between progression and frank AD. Dysfunctional bioenergetic pathways increased dysregulation as the AD spectrum progressed. Immune response pathways were more dysregulated in frank AD than prodromal stages. DEGs, = biological pathways, and interactomes demarcate specific stages across the AD spectrum.

BACKGROUND:fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. METHODS:fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. RESULTS:OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)- temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036). CONCLUSIONS:24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.

BACKGROUND:Individuals with attention deficit hyperactivity disorder (ADHD) are at a higher risk of depression and lower quality of life (QoL); however, it is unclear whether disrupted sleep and circadian rhythms mediate this increased risk. OBJECTIVES/OBJECTIVE:We investigated whether disruption of self-reported sleep and circadian factors mediate the associations of ADHD traits with depression symptom severity and QoL. METHODS:1364 participants (mean: 51.86 (SD=0.37) years, 75% women) from a large-scale cross-sectional online survey (Netherlands Sleep Registry) completed a sociodemographic questionnaire, the Adult ADHD Rating Scale, Hospital Anxiety and Depression Scale, Satisfaction With Life Scale (SLS) and Cantril Ladder (CL) (QoL measures), Insomnia Severity Index, Pittsburgh Sleep Quality Index and Munich Chronotype Questionnaire. FINDINGS/RESULTS:Higher ADHD traits were significantly associated with depression symptom severity (p=0.03), lower QoL (p<0.001), insomnia severity (p<0.001), lower sleep quality (p<0.001) and later chronotype (p=0.01). No sleep or circadian factor significantly mediated the association of the severity of symptoms of ADHD and depression (all p>0.1). Conversely, only insomnia severity significantly mediated the association of ADHD traits and QoL (SLS: standardised β=-0.10, 95% CI (-0.12 to -0.04); CL: standardised β=0.103, 95% CI (0.04 to 0.16)). CONCLUSION/CONCLUSIONS:ADHD traits were associated with lower QoL and it was partially mediated by insomnia severity. Future studies targeting insomnia complaints in this population may help mitigate their depression complaints and improve their QoL. CLINICAL IMPLICATIONS/CONCLUSIONS:Our results may help current clinical guidelines that do not typically link sleep/circadian complaints to QoL in ADHD assessment.