Faculty Bibliography

Background/UNASSIGNED:The Head Start treatment protocols have focused on curing young children with brain tumors while avoiding or delaying radiotherapy through using a combination of high-dose, marrow-ablative chemotherapy and autologous hematopoietic cell transplantation (AuHCT). Late effects data from treatment on the Head Start II (HS II) protocol have previously been published for short-term follow-up (STF) at a mean of 39.7 months post-diagnosis. The current study examines long-term follow-up (LTF) outcomes from the same cohort. Methods/UNASSIGNED:Eighteen HS II patients diagnosed with malignant brain tumors <10 years of age at diagnosis completed a neurocognitive battery and parents completed psychological questionnaires at a mean of 104.7 months' post-diagnosis. Results/UNASSIGNED:There was no significant change in Full Scale IQ at LTF compared to baseline or STF. Similarly, most domains had no significant change from STF, including verbal IQ, performance IQ, academics, receptive language, learning/memory, visual-motor integration, and externalizing behaviors. Internalizing behaviors increased slightly at LTF. Clinically, most domains were within the average range, except for low average mathematics and receptive language. Additionally, performance did not significantly differ by age at diagnosis or time since diagnosis. Of note, children treated with high-dose methotrexate for disseminated disease or atypical teratoid/rhabdoid tumor displayed worse neurocognitive outcomes. Conclusions/UNASSIGNED:These results extend prior findings of relative stability in intellectual functioning for a LTF period. Ultimately, this study supports that treatment strategies for avoiding or delaying radiotherapy using high-dose, marrow-ablative chemotherapy and AuHCT may decrease the risk of neurocognitive and social-emotional declines in young pediatric brain tumor survivors.

OBJECTIVE:Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. METHODS:We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. RESULTS:There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. CONCLUSION/CONCLUSIONS:Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Objectives: The history of racial discrimination against African American (AfAm) and Black people in the United States is deeply rooted in the history of this country. This presentation will help participants understand the intersection between racism, structural racism, and subsequent hardships as it relates to the AfAm youth's experience of discrimination. This presentation will also help participants learn practical approaches for exploring issues of discrimination with AfAm patients.
Method(s): The presenter will review the history of racial discrimination toward AfAm groups in the United States and give an overview of common experiences of discrimination for AfAm youth. Additionally, using the models of adolescent development of Erik Erikson, William Cross, James Marcia, and Beverly Tatum, the presenter will describe how racial prejudice impacts adolescent socialization and (racial) identity development, and the risk that this may confer for mental illness. Finally, the presenter will offer clinical pearls for clinicians to explore topics of racial and religious prejudice with AfAm patients.
Result(s): For AfAms, racism, segregation, and the resultant impacts on self-esteem and identity have been a constant reality and threat from the time of slavery through the present day. These brutal institutions, sanctioned and maintained by institutional racism, clearly manifest in all aspects of life for African Americans-segregated and unequal education system and housing, healthcare disparities, mental healthcare disparities, disproportionally elevated incarceration rates, and as painfully highlighted this past year, continued vulnerability to acts of violence at the hands of law enforcement. These disastrous long-term consequences have been documented and are clear. However, the experience of Black youth, introduced to these harsh realities over time, has strong implications during crucial periods of development, including physical, emotional, and identity development.
Conclusion(s): There is benefit for clinicians to incorporate exploration of the impact of racial discrimination, although it is challenging, in the evaluation and treatment of AfAm and Black youth. DEI, DEV, ADOL
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Objectives: There is a significant and urgent need across psychiatry and other academic medicine departments to design, create, and execute effective dialogues on race, while examining unconscious bias and privilege. The overarching goal of facilitated dialogue is to create a safe space for faculty, staff, and trainees of different racial backgrounds to engage in meaningful dialogue that helps all develop an antiracist approach to their work and lives.
Method(s): Based on the literature and the findings of a departmental needs assessment survey that we designed, we developed clear learning objectives, community norms, an 8-month curriculum, facilitator training and supervision, mixed-race dialogue group composition and logistics, and continuous improvement and comprehensive program evaluation. The curriculum covered topics spanning social identity, power and privilege, bias and discrimination, microaggressions, historical and structural racism, current events, cultural formulation and application to practice, allyship, and antiracism stance and action. Each facilitated dialogue session incorporated antiracist readings, videos, podcasts, immersive activities, and interactive group discussion.
Result(s): A total of 114 department faculty, staff, and trainees completed the antiracism education needs assessment survey. Ten clinical leaders were trained to serve as dialogue facilitators. Ninety-seven faculty, staff, and trainees from diverse sociodemographic backgrounds opted to participate, and 179 learner experience surveys were collected from October 2020 to January 2021. At least 94% of respondents felt engaged, safe in the dialogue environment, learned key antiracism concepts, and learned tools on how to take an antiracist stance in their work and lives.
Conclusion(s): Our curriculum, process, and facilitators have successfully addressed our goals of creating a safe space to discuss experiences with race and racism, staying open to the experiences of others, being open to new ways of viewing race, and furthermore use this new perspective to adopt an antiracist stance in their lives. Our workshop format is designed to help participants understand our process and to think through creating their own dialogues. It involves a mix of instructive and highly interactive activities, performed through breakouts and debriefings. AC, DEI, REST
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Stimulants (methylphenidate or amphetamines) are the recommended first-line option for the pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD). However, some patients with ADHD will not respond optimally to stimulants. Here, we discuss strategies to manage stimulant-refractory ADHD, based on the recommendations advanced in clinical guidelines, knowledge of expert practice in the field, and our own clinical recommendations, informed by a comprehensive literature search in PubMed, PsycInfo, EMBASE + EMBASE classic, OVID Medline, and Web of Science (up to 30 March 2021). We first highlight the importance of stimulant optimization as an effective strategy to increase response. We then discuss a series of factors that should be considered before using alternative pharmacological strategies for ADHD, including poor adherence, time action properties of stimulants (and wearing-off of effects), poor tolerability (that prevents the use of higher, more effective doses), excessive focus on or confounding from presence of comorbid non-ADHD symptoms, and tolerance. Finally, we consider the role of non-stimulants and combined pharmacological approaches. While the choice of medication for ADHD is still to a large extent based on a trial-and-error process, there are reasonably accepted data and guidelines to aid in clinical decision-making. It is hoped that advances in precision psychiatry in the years ahead will further guide prescribers to tailor medication choice to the specific characteristics of the patient.

Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer's disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex pathological interactions and dysregulated pathways that are poorly understood. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration. We utilized Ts65Dn mice to understand mechanisms underlying BFCN degeneration to identify novel targets for therapeutic intervention. We performed high-throughput, single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs, using laser capture microdissection to individually isolate ~500 choline acetyltransferase-immunopositive neurons in Ts65Dn and normal disomic (2N) mice at 6 months of age (MO). Ts65Dn mice had unique MSN BFCN transcriptomic profiles at ~6 MO clearly differentiating them from 2N mice. Leveraging Ingenuity Pathway Analysis and KEGG analysis, we linked differentially expressed gene (DEG) changes within MSN BFCNs to several canonical pathways and aberrant physiological functions. The dysregulated transcriptomic profile of trisomic BFCNs provides key information underscoring selective vulnerability within the septohippocampal circuit. We propose both expected and novel therapeutic targets for DS and AD, including specific DEGs within cholinergic, glutamatergic, GABAergic, and neurotrophin pathways, as well as select targets for repairing oxidative phosphorylation status in neurons. We demonstrate and validate this interrogative quantitative bioinformatic analysis of a key dysregulated neuronal population linking single population transcript changes to an established pathological hallmark associated with cognitive decline for therapeutic development in human DS and AD.

Objectives: Cannabis use disorder (CUD) is a common comorbidity in schizophrenia and affects the disease phenomenology. Given the heterogeneity and chronic course of schizophrenia, it is important to study the impact of CUD on healthcare utilization and outcomes in children with schizophrenia spectrum disorders. This study reports the demographic differences in a sample of inpatient children with schizophrenia and CUD, and analyzes its impact on the length of hospitalization.
Method(s): We used the nationwide inpatient sample within the Healthcare Cost and Utilization Project (HCUP) from the years 2012 to 2014. We identified patients with diagnoses of schizophrenia spectrum disorder and CUD using validated ICD-9 and Clinical Modification codes. Pearson chi² test and student's t test were used to assess categorical and continuous variables, respectively.
Result(s): We analyzed 6518 inpatient children with a diagnosis of schizophrenia spectrum disorder from 2012 to 2014. The prevalence of CUD was 1.7%. There was a relatively stable trend of CUD in children from 2012 to 2014 of 1.6%, except for a spike of 2% in the year 2013. The mean age for children with schizophrenia and CUD is 15.54 +/- 2.5 years (p < 0.00). CUD was higher in males (81.3%) than females (18.8%) (p < 0.00) with predominance in African American (37%) and White (35.9%) patients. The mean length of hospitalization was 11.5 +/- 18.54 days (p = 0.36). We further categorized this sample with comorbid suicidal ideations and found that 2.2% (n = 35) of them had CUD. The mean age for children with schizophrenia having suicidal ideation and CUD is 15.71 +/- 1.8 years (p < 0.00). CUD was higher in males (60%) than females (40%) (p = 0.16) with predominance in White (53.8%) and African American (26.9%) patients. The mean length of hospitalization was 8.5 +/- 8.9 days (p = 0.679).
Conclusion(s): Our study found almost consistent trends of CUD in children with schizophrenia between 2012 and 2014, which indicates the necessity to develop interventions and programs to target CUD and resulting healthcare expenditure. There is a need to explore the biological and psychological mechanisms behind the preponderance of cannabis use in males and to identify the gender- and race-specific risk factors to mitigate the long-term adversities. SUD, SZ, S
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Objectives: Undergraduate college courses on well-being have proliferated in the United States, but there are few data examining whether they have an impact on student well-being or mental health. This study examined the impact of such a course on students' well-being and grade point average (GPA) compared to students who completed a psychology course on psychopathology.
Method(s): Participants were 152 undergraduates enrolled in the "Science of Happiness" (SOH), which focuses on well-being and mental health challenges (n = 64), and "Child and Adolescent Psychopathology" (CAP), a psychology course (n = 88). Well-being measures were collected using validated questionnaires (PERMA Profiler [PP], Satisfaction with Life Scale [SWLS]) at the beginning of the semester and at the completion of the semester. Both t tests and linear regression examined the effect of the courses on the outcomes.
Result(s): At baseline, there were no statistically significant differences in well-being or grades between the 2 groups. Examining the pre/post-SOH changes, we found statistically significant improvements on the SWLS (M = 1.28; SD = 4.85; t63 = 2.11; p < 0.04) and in GPA (M = 0.07; SD = 0.17; t72 = 3.47; p < 0.001). The improvement in the PP Well-being was not significant for either SOH or CAP but trended positive for SOH (M = 0.05) and negative for CAP (M = -0.05). In CAP, there was no statistically significant improvement in SWLS, but GPA change was statistically significant (M = 0.04; SD = 0.14; t96 = 2.99; p < 0.004). When we examined the pre-/postdifferences between the 2 groups, we found no statistical significance for SWLS or GPA.
Conclusion(s): Given the prevalence of mental health challenges in college students and the need for effective, large-scale prevention interventions for this population, courses on well-being are a strategy that warrant further exploration. PRE, COLST, SC
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