Faculty Bibliography

OBJECTIVE/UNASSIGNED:To examine the effects of Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) on ADHD symptoms throughout the day in adults with DSM-5 ADHD. METHOD/UNASSIGNED:This was a 6-week pilot study that included 3 weeks of open label treatment with SDX/d-MPH (39.2/7.8 mg/day to 52.3/10.4 mg/day in clinical titration) after completion of a one-week screening period and a two-week observation period in seventeen adults with ADHD. Two subjects were discontinued from the trial, one for being placebo-responder and another for exhibiting blood pressure lability during the observation period. Of the remaining 15 subjects, one dropped out after one week on 39.2/7.8 mg/day, while all others completed the trial. All fifteen participants were included in the data analyses. RESULTS/UNASSIGNED:There were substantial effects of SDX/d-MPH on all clinical measures, including investigator symptom scores (AISRS); self-report (ASRS) scores, time-sensitive ADHD (TASS) scores throughout the day, impairment (CGI) and executive function scores (BRIEF-A) and measures of medication smoothness (AMSES). SDX/d-MPH was generally well tolerated. CONCLUSIONS/UNASSIGNED:This pilot study is the first systematic treatment effect trial data for SDX/d-MPH in adults with DSM-5 ADHD. The data preliminarily supports the clinical efficacy of DSM/d-MPH in adult ADHD and its ability to ameliorate symptoms throughout the day.

OBJECTIVE:Childhood inhibited temperament (cIT) is associated with an increased risk for developing internalizing psychopathology. Neurobiological characteristics identified by structural magnetic resonance imaging (MRI) may elucidate the neural substrates for cIT, but studies are scarce and often focus on particular regions of interest. Moreover, current findings lack replication. This pre-registered analysis from the ENIGMA-Anxiety Working Group examined structural brain characteristics associated with cIT using a comprehensive whole-brain approach. METHOD/METHODS:Temperament assessments (behavioral observations, parental/teacher reports or self-reports on cIT before age 13) and MRI-data (age at scan: 6-25 years) from international research sites (Europe, North America, South America) were pooled for mega-analysis. Following image processing and quality control, associations between cIT and brain structure were examined in 3,803 participants. Subcortical volumes, cortical thickness and surface area (main analyses) and detailed subcortical characteristics (e.g. subnuclei, subfields, partial volume effects; exploratory analyses) were considered. RESULTS:= 0.029) in youth with parental/teacher reports on cIT-levels. Exploratory analyses revealed findings in hippocampus, putamen and caudate, but most did not survive statistical correction for multiple testing. CONCLUSION/CONCLUSIONS:This mega-analysis found no consistent associations between cIT and regional brain structure, although the role of parietal regions warrants further investigation. Future studies should consider brain function in cIT, preferably using longitudinal designs.

OBJECTIVE/UNASSIGNED:The Houston Conference Guidelines (Hannay et al., 1998) provided an initial framework for North American neuropsychology training that served the specialty well for several decades. Subsequent advances in technology, increased diversity of the U.S. and Canadian populations, and the adoption of competency-based training models within Health Service Psychology have created a need to update neuropsychology training guidelines. Therefore, in 2022, the Minnesota Conference to Update Education and Training Guidelines in Clinical Neuropsychology began a two-year drafting process leading to the currently proposed update. METHOD/UNASSIGNED:A Steering Committee worked with content experts, consultants, and delegates representing North American neuropsychological organizations and specialists. The final version of the guidelines was developed after reviewing neuropsychological training literature, gathering feedback from specialists, and making iterative revisions of earlier drafts to reach consensus. CONCLUSION/UNASSIGNED:The resulting "Minnesota Guidelines" include five foundational (Neuroscience and Brain Behavior Relationships; Integration of Science and Practice; Ethics, Standards, Laws, and Policies; Diversity; and Professional Relationships) and eight functional (Assessment; Intervention; Interdisciplinary Systems and Consultation; Research and Scholarship; Technology and Innovation; Teaching, Supervision, and Mentoring; Health and Professional Advocacy; and Administration, Management, and Business) areas of competency required for entry level specialty practice. While consensus was not achieved, a majority of voting delegates recommended the Guidelines for adoption and the Guidelines have been endorsed by six neuropsychology education and board certification organizations. The American Academy of Clinical Neuropsychology has not endorsed the Minnesota Guidelines and will not make an endorsement decision until three months after online publication.

IMPORTANCE/UNASSIGNED:Representation of race and ethnicity in randomized clinical trials (RCTs) is critical for understanding treatment efficacy across populations with different racial and ethnic backgrounds. OBJECTIVE/UNASSIGNED:To examine race and ethnicity representation and reporting across RCTs of pharmacotherapies for mental disorders. DATA SOURCES/UNASSIGNED:PubMed (Medline), Embase (Ovid), APA PsycInfo, and Web of Science were searched until March 1, 2024, to retrieve network meta-analyses including RCTs of pharmacotherapies for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision mental disorders. STUDY SELECTION/UNASSIGNED:RCTs that recruited people of any age with a diagnosis of a mental disorder and that tested the efficacy of any pharmacologic intervention vs any control arm. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Random-effects logit-transformed proportion meta-analyses were used to estimate prevalence rates of race and ethnicity groups and their temporal trends across RCTs and to compare US RCT prevalence rates with US Census data. The Preferred Reporting Items for Overviews of Reviews was used to report our review. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Reporting of data and percentages of race and ethnicity. The year of publication, type of RCT, geographic location, age group, and sample size were also included. There were no deviations that occurred from the original protocol. RESULTS/UNASSIGNED:Data were obtained from 1683 RCTs (375 120 participants in total). Of these, 1363 (91.7% of participants) included participants aged 18 years or older; 680 RCTs (36.0% of participants) were from the US, 404 (17.1% of participants) were from Europe, and 293 (29.9% of participants) were from multiple geographic locations. Race and ethnicity were reported in 39.2% of RCTs; reporting was the highest in US-based RCTs (58.7%) and lowest in Central and South America (8.7%) and Asia and the Middle East (12.4%). Among participants, 2.7% (95% CI, 2.1%-3.5%) self-reported as Asian, 9.0% (95% CI, 8.1%-10.0%) as Black, 11.0% (95% CI, 9.1%-13.3%) as Hispanic among White, 80.2% (95% CI, 78.8%-81.5%) as White including Hispanic, and 5.8% (95% CI, 5.2%-6.4%) as other race or ethnicity, multiracial, or multiethnic. There was more frequent reporting of race and ethnicity in US RCTs (log odds increased by 0.066 each year) and less frequent reporting in non-US RCTs (log odds increased by 0.023 each year). Studies reporting race and ethnicity did not generally include larger sample sizes (mean sample size, 263.7 [95% CI, 15.0-860.3] participants) compared with those not reporting such data (mean sample size, 196.6 [95% CI, 12.0-601.3] participants), albeit not in all locations. In US RCTs, adults in the other or multiracial and multiethnic category were historically overrepresented, while adults in Asian, Black, Hispanic among White, and White including Hispanic categories were underrepresented; Asian, Black, and Hispanic among White children and adolescents are still currently underrepresented. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of this meta-analysis suggest that differences in reporting race and ethnicity across geographic locations and underrepresentation of certain racial and ethnic groups in US-based RCTs highlight the need for international guidelines to ensure equitable recruitment and reporting in clinical trials.

OBJECTIVES/OBJECTIVE:To document the proportion of transgender and gender diverse (TGD) youth presenting to a pediatric psychiatric emergency department (ED) and examine whether their demographic and clinical characteristics differ from cisgender youth. METHODS:We analyzed electronic health records of youth ages 5 to 17 years presenting to a specialized pediatric psychiatric ED (N = 2728), including sociodemographic characteristics, gender identity, suicidal risk at admission, and diagnoses at discharge. We examined differences by gender identity using χ2 tests (categorical variables), 2-sample t tests, or Mann-Whitney U tests (continuous variables). Adjusted Poisson regression models estimated the prevalence ratio of the association between gender identity and clinical diagnoses. RESULTS:Of youth, 6% seeking emergency psychiatric care identified as TGD. Compared with cisgender peers, TGD youth exhibited a higher risk for suicide, longer hospital stays, and received more psychiatric diagnoses at discharge, including a higher prevalence of suicidal thoughts and behaviors (prevalence ratio: 1.50, 95% CI: 1.16, 1.90). CONCLUSIONS:TGD youth have more severe clinical presentations in the psychiatric ED compared with cisgender youth. Further research is essential to develop targeted interventions to support the mental health of TGD youth.

Individual differences in how the brain responds to novelty are present from infancy. A common method of studying novelty processing is through event-related potentials (ERPs). While ERPs possess millisecond precision, spatial resolution remains poor, especially in infancy. This study aimed to balance spatial and temporal precision by combining ERP data with functional magnetic resonance imaging (fMRI) data. Twenty-nine infants (15 female) underwent resting-state fMRI (M

Group preventative parent training programs (PPTPs) have been used successfully to improve outcomes for families living in poverty in settings such as Head Start. Nevertheless, such programs face significant enrollment and engagement challenges. Given that research on factors related to parent preferences for group PPTP participation is limited, the purpose of the current study is to examine what types of programs are most preferred by a combined sample of English and Spanish speaking Head Start parents, and to translate program modeling of parent preferences into feasible programming options. The current study relies on conjoint analysis, a technique derived from market research, to learn more about how Head Start parents leverage attributes of a parenting program when making hypothetical participation decisions. Based on a discrete choice experiment with 234 urban, Early Head Start and Head Start parents, findings indicate that parents prioritize program attributes that target strong improvements for their children on desired outcomes, such as academics and friendship skills, while also offering incentives for participation. Simulations indicated that 77.6% of parents preferred an Optimizing Outcomes Program, while 22.4% preferred a Foundational Needs Program. Finally, results indicate that child prosocial or difficult behavior and parent depression risk are associated with specific program preferences. Parents with fewer resources prefer programs that are more foundational and realistic to target more modest gains. Implications are discussed in terms of program modeling and offering programs tailored to preferences.

Fetal iron status has long-lasting effects on neurodevelopmental outcomes and risk of psychopathology. Although prenatal exposure to maternal psychological stress has been linked to offspring peripheral iron status at birth, it is unknown whether maternal prenatal stress is related to fetal brain iron during gestation. We utilized 86 multi-echo functional magnetic resonance imaging (fMRI) scans from 52 fetuses (23 females; gestational age [GA] 24-38 weeks) to estimate R2* relaxometry as a proxy for fetal brain iron levels. Our results showed that greater maternal anxiety symptoms were associated with higher estimated fetal iron levels in the left cerebellar vermis after controlling for fetal sex and GA. Our finding suggests that fetal brain iron levels may be sensitive to exposure to maternal stress in utero. In a subset of participants with available infant outcome data (n = 31), no significant associations were found between fetal brain iron levels and later cognitive, language, and motor development during infancy. Overall, this study presents the first evidence of associations between maternal prenatal stress and fetal brain iron, which lays the groundwork for future investigations of biological embedding of prenatal maternal stress on the fetal brain and later neurodevelopment through prenatal iron accumulation as a potential mechanism.

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.

Assessment of psychiatric symptoms relies on subjective self-report, which can be unreliable. Digital phenotyping collects data from smartphones to provide near-continuous behavioral monitoring. It can be used to provide objective information about an individual's mental state to improve clinical decision-making for both diagnosis and prognostication. The goal of this study was to evaluate the feasibility and acceptability of smartphone-based digital phenotyping for long-term mental health monitoring in adolescents with bipolar disorder and typically developing peers. Participants (aged 14-19) with bipolar disorder (BD) or with no mental health diagnoses were recruited for an 18-month observational study. Participants installed the Beiwe digital phenotyping app on their phones to collect passive data from their smartphone sensors and thrice-weekly surveys. Participants and caregivers were interviewed monthly to assess changes in the participant's mental health. Analyses focused on 48 participants who had completed participation. Average age at baseline was 15.85 years old (SD = 1.37). Approximately half (54%) identified as female, and 54% identified with a minoritized racial/ethnic background. Completion rates across data types were high, with 99% (826/835) of clinical interviews completed, 89% of passive data collected (22,233/25,029), and 47% (4,945/10,448) of thrice-weekly surveys submitted. The proportion of days passive data were collected was consistent over time for both groups; the clinical interview and active survey completion decreased over the study course. Results of this study suggest digital phenotyping has significant potential as a method of long-term mental health monitoring in adolescents. In contrast to traditional methods, including interview and self-report, it is lower burden and provides more complete data over time. A necessary next step is to determine how well the digital data capture changes in mental health to determine the clinical utility of this approach.