Faculty Bibliography

In a previous study, dasotraline demonstrated efficacy at a dose of 8 mg/day in adults with attention deficit hyperactivity disorder (ADHD). The aim of the current study was to evaluate the efficacy and safety of dasotraline in doses of 4 and 6 mg/day. Adults meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for ADHD were randomized to 8 weeks of double-blind, once-daily, fixed-dose treatment with dasotraline 4 mg/day, 6 mg/day, or placebo. The primary efficacy endpoint was changed in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy endpoints included the Clinical Global Impression, Severity (CGI-S) Scale. Least squares mean reduction at week 8 in the ADHD RS-IV HV total score was not significantly greater (vs. placebo) in the dasotraline 4 mg/day group (-15.0 vs. -13.9; n.s.; or in the dasotraline 6 mg/day group (-16.5 vs. -13.9; P = 0.074; Hochberg correction). Treatment with dasotraline 6 mg/day was significant at week 8 (uncorrected) on the ADHD RS-IV total score (P = 0.037) and the CGI-S score (P = 0.011). Treatment with the 4 mg/day dose of dasotraline was NS. Treatment with dasotraline was generally well tolerated. The results provide additional evidence that supports the potential efficacy of dasotraline, in doses of 6 mg/day, in adults with ADHD.

Background: Autism spectrum disorder (ASD) is a highly prevalent developmental disorder. There is notable disparity in occurrence rates between males and females, with males being 4.5 times as likely as their female counterparts to be diagnosed with the disease. A major objective for improving functional outcomes in ASD is to isolate biomarkers for earlier detection; an area as yet unexplored is whether biomarkers of future ASD symptomology may be observable in the fetal brain. Here, we focus on the amygdala, which shows sex-differential patterns of development and has been implicated in the neurobiology of ASD.
Method(s): We obtained resting-state MRI data in 109 healthy human fetuses (24-39 weeks) and Brief Infant Toddler Social Emotional Assessment (BITSEA) and Child Behavior Checklist (CBCL) measures at child age 3. The average number of frames obtained after scrubbing high-motion frames was N=169, or 5.6 minutes of resting state data (TR=2) with mean XYZ motion 0.9mm (SD=0.3). Subject-specific amygdala connectivity maps were computed and tested in a full factorial model, that included sex, age at scan, and ASD outcome.
Result(s): ASD outcomes were associated with increased amygdala connectivity to prefrontal and sensorimotor cortices, decreased connectivity to anterior insula and cerebellum, and sex interactions were observed in inferior prefrontal and striatal regions (p<0.005 and k min=25).
Conclusion(s): These observations raise exciting new ideas about the advent of risk and the ontogeny of early sex differences. Further analyses will be conducted to examine sex-differential risk and postnatal environmental effects within a multifactorial liability model framework. Supported By: NIMH R01 MH110793 NIDA R34 DA050287 NIMH R01 MH122447 NARSAD Foundation Keywords: Fetal, Autism, Resting-State, Sex Differences
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BACKGROUND:This study examined trauma screening and behavioral health linkage rates in school-based health centers (SBHCs). METHODS:Participants included 4161 English- and Spanish-speaking patients between the ages of 12 and 22 across 8 urban SBHCs 2 years. Screening rates at medical visits and linkage to additional behavioral health screening and services were assessed via electronic medical records and a chart audit. RESULTS:Medical providers administered the Primary Care-PTSD screen to 66.3% of patients in year 1 and 46.7% of patients in year 2. Rates of positive trauma screens were 27.5% and 32.1%, respectively, with more girls screening positive than boys. Few (year 1; 8.1%; year 2: 9.6%) adolescents received additional trauma screening by a behavioral health clinician. However, the majority were linked to services (year 1: 66%; year 2: 74%). Lack of documentation (year 1: 24%; year 2: 33%) was a common gap in the charts of patients who did not receive a second stage trauma screening. Demographic differences in screening rates were minimal. CONCLUSION/CONCLUSIONS:The current study supports the feasibility of traumatic stress screening and linkage within an integrated care setting. Process improvement efforts should, however, address communication gaps around trauma assessment and its integration into ongoing care.

The COVID-19 pandemic exacerbates the mental, emotional, and behavioral (MEB) health problems of children and adolescents in the United States (U.S.). A collective and coordinated national economic and social reconstruction effort aimed at shoring up services to promote children's MEB, like the Marshall Plan that helped rebuild Europe post-World War II, has been proposed to buttress against the expected retrenchment. The plan prioritizes children's well-being as a social objective. We propose strategically reconstructing the public safety-net systems serving youth, including early education, maternal and child health, child welfare, corrections, and mental health. That plan called for a concentrated focus on coalition-building and contracting by state mental health systems to establish a foundation for an improved health system. This paper offers a complementary set of suggestions for the four non-mental health systems mentioned above by recommending actionable steps based on scientific evidence to support improved services for children at risk for MEB problems. For each system we describe examples of evidence-informed services, policies or programs that (1) prevent disabilities and promote health, (2) protect and preserve families and neighborhoods, and (3) provide quality care. Prioritizing the promotion of children's MEB health by all state systems can shape U.S. children's health and well-being for generations to come.

The current study examined relations between distinct aspects of moral functioning, and their cognitive and emotional correlates, in preschool age children. Participants were 171 typically developing 3- to 6-year-olds. Each child completed several tasks, including (a) moral tasks assessing both performance of various moral actions and evaluations of moral scenarios presented both verbally and nonverbally; and (b) non-moral tasks assessing general cognitive skill, executive functioning, theory-of-mind, and emotion recognition. Shyness and empathic concern were assessed from video acquired during participation. Results demonstrated positive associations among distinct moral actions, as well as among distinct moral evaluation tasks, but few associations between tasks assessing moral actions and moral evaluation. Empathic concern and inhibitory control each emerged as important predictors of preschoolers' moral functioning.

Symptoms of attention-deficit/hyperactivity disorder (ADHD) in elementary school-age children are associated with poor relationships with classroom peers, as indicated by poor social preference, low peer support, and peer victimization. Less is known about how friendship patterns relate to ADHD symptoms, or how friendships may buffer risk for negative peer experiences. Participants were 558 children in 34 classrooms (grades K-5). At the beginning (fall) and end (spring) of an academic year, children completed (a) sociometric interviews to index friendship patterns and social preference, and (b) self-report questionnaires about their support and victimization experiences from classmates. In fall, higher teacher-reported ADHD symptoms were associated with children having more classmates with no friendship ties (non-friends) and who the child nominated but did not receive a nomination in return (unreciprocated friends), and with having fewer classmates with mutual friendship ties (reciprocated friends) and who nominated the child but the child did not nominate in return (unchosen friends). Higher fall ADHD symptoms predicted more non-friend classmates, poorer social preference, and more victimization in the spring, after accounting for the same variables in fall. However, having many reciprocated friends (and to a lesser extent, many unchosen friends) in fall buffered against the trajectory between fall ADHD symptoms and poor peer functioning in spring. By contrast, having many unreciprocated friends in fall exacerbated the trajectory between fall ADHD symptoms and poor peer functioning in spring. Thus, elevated ADHD symptoms are associated with poorer friendship patterns, but reciprocated friendship may protect against negative classroom peer experiences over time.

The everyday world is populated with artifacts that require specific motor actions to use objects as their designers intended. But researchers know little about how children learn to use everyday artifacts. We encouraged forty-four 12- to 60-month-old children to unzip a vinyl pouch during a single 60-s trial. Although unzipping a pouch may seem simple, it is not. Unzipping requires precise role-differentiated bimanual actions-one hand must stabilize the pouch while the other hand applies a pulling force on the tab. Moreover, kinematic data from six adults showed that the tolerance limits for applying the forces are relatively narrow (pulling the tab within 63° of the zipper teeth while stabilizing the pouch within 4 cm of the slider). Children showed an age-related progression for the unzipping action. The youngest children did not display the designed pulling action; children at intermediate ages pulled the tab but applied forces outside the tolerance limits (pulled in the wrong direction, failed to stabilize the pouch in the correct location), and the oldest children successfully implemented the designed action. Findings highlight the perceptual-motor requirements in children's discovery and implementation of the hidden affordances of everyday artifacts.

Cerebrovascular reactivity (CVR) is of great significance for the treatment and prevention of cerebrovascular diseases. CVR can be mapped using the blood oxygenation level-dependent (BOLD) signal of fMRI. Breath holding (BH) is a reliable method to produce the desired increase in arterial CO₂, while its application in clinical research is limited due to subject's compliance and variability. BH task with variable respiratory rates could allow more flexibility in clinical populations. In this study, 50 healthy volunteers were scanned for end-inspiration BH tasks with three different respiration rates. For the three respiratory rates BH tasks, the CVR was estimated based on the BOLD signal and general linear model (GLM) separately. Specifically, the extra time delay was considered for the hemodynamic response function, and the optimal delay was estimated for each voxel. To measure CVR in grey matter, BOLD signals of end-inspiration BH were used as regressors in general linear models to quantify their impact on CVR. This was performed for regions and voxels. Systematic differences were observed between the three end-inspiratory breathing rates. The greatest increase in activation intensity was found in fast breathing followed by self-paced and slow breathing. We conclude that the BH task of variable respiratory rates allows for CVR measurement, making breath-holding challenges more flexible and appropriate for routine practice.