Faculty Bibliography

Evidence suggests that differences in motor function are an early feature of autism spectrum disorder (ASD). One aspect of motor ability that develops during childhood is postural control, reflected in the ability to maintain a steady head and body position without excessive sway. Observational studies have documented differences in postural control in older children with ASD. The present study used computer vision analysis to assess midline head postural control, as reflected in the rate of spontaneous head movements during states of active attention, in 104 toddlers between 16-31 months of age (Mean = 22 months), 22 of whom were diagnosed with ASD. Time-series data revealed robust group differences in the rate of head movements while the toddlers watched movies depicting social and nonsocial stimuli. Toddlers with ASD exhibited a significantly higher rate of head movement as compared to non-ASD toddlers, suggesting difficulties in maintaining midline position of the head while engaging attentional systems. The use of digital phenotyping approaches, such as computer vision analysis, to quantify variation in early motor behaviors will allow for more precise, objective, and quantitative characterization of early motor signatures and potentially provide new automated methods for early autism risk identification.

OBJECTIVES/OBJECTIVE:There is a need for brief and publicly-available assessments of attention deficit hyperactivity disorder (ADHD) easily administered in large-scale survey efforts monitoring symptoms among adolescents. The ADHD Self-Report Scale v1.1 (ASRS; Kessler et al., 2005) Screener, a six-item measure of ADHD symptoms, is a valid and reliable screening instrument for ADHD among adults. The current study provides initial evidence for the reliability and validity of the ASRS Screener among a community sample of U.S. adolescents. METHODS:Middle and high school students in grades 6 through 12 (N = 2,472) completed the ASRS Screener, along with the Strengths and Difficulties Questionnaire (SDQ; Goodman, 2001) and several questions about school functioning. RESULTS:The ASRS Screener demonstrated good internal consistency, with items captured by a single underlying latent variable, which was invariant across subsamples differing by gender. The ASRS Screener scores were associated with the SDQ subscale measuring hyperactivity/inattention (r = 0.58) and significantly less strongly associated with other SDQ subscale scores (r = -0.15-0.41). The ASRS Screener scores were also significantly associated with student-reported school functioning. CONCLUSION/CONCLUSIONS:Findings suggest directions for future research and provide preliminary support for use of the ASRS Screener as a brief tool for identifying symptoms of ADHD among adolescents.

INTRODUCTION/BACKGROUND:(MPH-ERCT) is an ER methylphenidate designed to be chewed before swallowing. The technology and pharmacokinetics, along with efficacy and safety data, are presented. Expert opinion: Extensive safety and efficacy data exist for MPH. ER formulations can be distinguished by preparation (tablet, capsule, liquid) and onset and duration of effect, but efficacy is similar for all ER MPH products. Each formulation has attributes, such as ease of titration, portability, and taste, that make it more acceptable for certain patients. Because AMPH and MPH are so effective, current technology research is focused on improving safety, convenience, and onset and duration of effect.

Early life trauma is a risk factor for life-long disorders related to emotional processing, but knowledge underlying its enduring effect is incomplete. This study was motivated by the hypothesis that early life trauma increases amygdala-dependent threat responses via reduction in inhibition by parvalbumin (PV) interneurons and perineuronal nets (PNN) supporting PV cells, thus increasing excitability of the basolateral amygdala (BLA). From postnatal day (PN) 8-12, rat pups of both sexes were reared under normal bedding or under insufficient nest-building materials to induce maternal-to-infant maltreatment trauma (Scarcity-Adversity Model, SAM). At weaning age of PN23, the SAM group exhibited increased threat responses to predator odor. The SAM-induced increase in threat response was recapitulated in normally reared PN22-23 rats that were unilaterally depleted of PNN in the BLA by the enzymes, chondroitinase-ABC plus hyaluronidase at PN19-20. Light and electron microscopic analysis of the BLA revealed that anterior-to-mid levels of SAM group's BLAs exhibited decreased PNN intensity and decreased axo-somatic synapses between PV-to-principal pyramidal-like neurons and PV-to-PV. PV and PNN densities (cells/ mm² ) in the BLA of both control (CON) and SAM groups were still low at PN12 and SAM delayed the ontogenetic rise of PV intensity and PNN density. Moreover, PV cell density in the anterior-to-mid BLA correlated negatively with threat response of CON animals, but not for SAM animals. Thus, reduction of PNN-supported, PV-mediated somatic inhibition of pyramidal cells provides a mechanistic support for the enduring effect of early life maltreatment manifested as increasing innate threat response at weaning.

Treatment response heterogeneity poses serious challenges for selecting treatment for many diseases. To better understand this heterogeneity and to help in determining the best patient-specific treatments for a given disease, many clinical trials are collecting large amounts of patient-level data prior to administering treatment in the hope that some of these data can be used to identify moderators of treatment effect. These data can range from simple scalar values to complex functional data such as curves or images. Combining these various types of baseline data to discover "biosignatures" of treatment response is crucial for advancing precision medicine. Motivated by the problem of selecting optimal treatment for subjects with depression based on clinical and neuroimaging data, we present an approach that both (1) identifies covariates associated with differential treatment effect and (2) estimates a treatment decision rule based on these covariates. We focus on settings where there is a potentially large collection of candidate biomarkers consisting of both scalar and functional data. The validity of the proposed approach is justified via extensive simulation experiments and illustrated using data from a placebo-controlled clinical trial investigating antidepressant treatment response in subjects with depression.

What is the evidence that 'pro re nata' (PRN) medication is effective for ending agitated outbursts in children and adolescents in psychiatric emergency rooms or inpatient units? Literature search was performed for studies of PRN medication use in children and adolescents that included an outcome measure. One randomised controlled trial, three prospective studies and six retrospective studies that included some outcome measure were identified. Outcome measures were heterogeneous, and frequently did not use standardised metrics assessing agitation level to measure effectiveness. The single small Randomized Controlled Trial (RTC) does not find a difference between placebo and medication, and outcomes of other studies do not control for potential placebo effect of the intervention itself as opposed to the medication. There is insufficient evidence to support the common practice of PRN medications for the management of acute agitation, and no data with which to inform clinical practice, such as which medicines and doses are helpful for specific populations or situations. Psychiatrists have no evidence-based medication interventions for acutely managing agitated outbursts in children and adolescents.

Resting state functional magnetic resonance imaging studies of psychosis have focused primarily on the amplitude of low-frequency fluctuations in the blood oxygen level dependent (BOLD) signal ranging from .01 to 0.1 Hz. Few studies, however, have investigated the amplitude of frequency fluctuations within discrete frequency bands and higher than 0.1 Hz in patients with psychosis at different illness stages. We investigated BOLD signal within three frequency ranges including slow-4 (.027-.073 Hz), slow-3 (.074-0.198 Hz) and slow-2 (0.199-0.25 Hz) in 89 patients with either first-episode or chronic psychosis and 119 healthy volunteers. We investigated the amplitude of frequency fluctuations within three frequency bands using 47 regions-of-interest placed within 14 known resting state networks derived using group independent component analysis. There were significant group x frequency interactions for the visual and motor cortex networks, with the largest significant group differences (patients < healthy volunteers) evident in slow-4 and slow-3, respectively. Also, healthy volunteers had an overall higher amplitude of frequency fluctuations compared to patients across the three frequency ranges in the visual cortex, dorsal attention and motor cortex networks with the opposite effect (patients > healthy volunteers) evident within the salience and frontal gyrus networks. Subsequent analyses indicated that these effects were evident in both first-episode and chronic patients. Our study provides new data regarding the importance of BOLD signal fluctuations within different frequency bands in the neurobiology of psychosis.

OBJECTIVES/OBJECTIVE:This study aimed to understand if maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) is associated with delayed language development among very young children ("toddlers"). METHODS:Data were collected from 61 mothers and toddlers (ages 12-42 months, mean age = 25.6 months SD = 8.70). Child expressive and receptive language development was assessed by the Ages and Stages Questionnaire (ASQ) communication subscale (ASQCS) that measures language acquisition. Observed maternal caregiving behavior was coded from videos of 10-min free-play interactions via the CARE-Index. Correlations, Mann-Whitney tests, and multiple linear regression were performed. RESULTS:There was no significant association between maternal IPV-PTSD severity and the ASQCS. Maternal IPV-PTSD severity was associated with continuous maternal behavior variables (i.e. sensitive and controlling behavior on the CARE-Index) across the entire sample and regardless of child gender. Maternal sensitivity was positively and significantly associated with the ASQCS. Controlling behavior was negatively and significantly associated with the ASQCS. CONCLUSIONS:Results are consistent with the literature that while maternal IPV-PTSD severity is not associated with child language delays, the quality of maternal interactive behavior is associated both with child language development and with maternal IPV-PTSD severity. Further study is needed to understand if the level of child language development contributes to intergenerational risk or resilience for relational violence and/or victimization.

OBJECTIVE:The serotonin (5-hydroxytryptamine [HT]) system has long been implicated in autism spectrum disorder (ASD). Whole-blood 5-HT level (WB5-HT) is a stable, heritable biomarker that is elevated in more than 25% of children with ASD. Recent findings indicate that the maternal 5-HT system may influence embryonic neurodevelopment, but maternal WB5-HT has not been examined in relation to ASD phenotypes. METHOD:WB5-HT levels were obtained from 181 individuals (3-27 years of age) diagnosed with ASD, 99 of their fathers, and 119 of their mothers. Standardized assessments were used to evaluate cognitive, behavioral, and language phenotypes. RESULTS: = 17.394, p < .001). Paternal and proband WB5-HT did not differ between classes. CONCLUSION:Maternal WB5-HT is associated with neurodevelopmental outcomes in offspring with ASD. Prospective, longitudinal studies will be needed to better understand the relationship between the function of the maternal serotonin system during pregnancy and brain development. Further studies in animal models may be able to reveal the mechanisms underlying these findings.