Faculty Bibliography

The frequent co-occurrence of anxiety disorders and autism spectrum disorders (ASD) in youth has spurred study of intervention practices for this population. As anxiety disorders in the absence of ASD are effectively treated using cognitive-behavioral therapy (CBT) protocols, an initial step in evaluating treatments for comorbid youth has necessarily centered on adaptation of CBT. One primary limitation of this research, to date, is that interventions for adolescents with anxiety disorders and ASD have not been systematically tested. In this study, 20 adolescents (90% male) with ASD and a comorbid anxiety disorder, between ages 11 and 14 years (M = 12.2 years, SD = 1.11 years), participated in an open trial of modified CBT targeting anxiety with ASD. Findings demonstrated significant reductions in anxiety severity, as assessed by clinician and parent ratings, from baseline to post-treatment. In addition, reductions in parent-rated externalizing symptoms were observed. Gains were maintained at a 1-month follow-up.

Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, which binds p75(NTR). In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75(NTR). Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD) in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral symptoms that emerge during the first years of life. Associated with these symptoms are differences in the structure of a wide array of brain regions, and in the connectivity between these regions. However, the use of cohorts with large age variability and participants past the generally recognized age of onset of the defining behaviors means that many of the reported abnormalities may be a result of cascade effects of developmentally earlier deviations. This study assessed differences in connectivity in ASD at the age at which the defining behaviors first become clear. There were 113 24-month-old participants at high risk for ASD, 31 of whom were classified as ASD, and 23 typically developing 24-month-old participants at low risk for ASD. Utilizing diffusion data to obtain measures of the length and strength of connections between anatomical regions, we performed an analysis of network efficiency. Our results showed significantly decreased local and global efficiency over temporal, parietal and occipital lobes in high-risk infants classified as ASD, relative to both low- and high-risk infants not classified as ASD. The frontal lobes showed only a reduction in global efficiency in Broca's area. In addition, these same regions showed an inverse relation between efficiency and symptom severity across the high-risk infants. The results suggest delay or deficits in infants with ASD in the optimization of both local and global aspects of network structure in regions involved in processing auditory and visual stimuli, language and nonlinguistic social stimuli.

In this paper, we propose an implementation science research agenda as it applies to school mental health (SMH). First, we provide an overview of important contextual issues to be considered when addressing research questions pertinent to the implementation of mental health interventions in schools. Next, we critically review three core implementation components: (a) professional development and coaching for school professionals regarding evidence-based practices (EBPs); (b) the integrity of EBPs implemented in schools; and (c) EBP sustainment under typical school conditions. We articulate research questions central to the next generation of research in each of these areas as well as methods to address such questions. Our intent in doing so is to contribute to a developing blueprint to guide community-research partnerships as well as funding agencies in their efforts to advance implementation science in SMH.

Background: Epidemiological data indicate that rates of pediatric bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) have increased dramatically over the past two decades. Overlapping diagnostic criteria contribute to concerns about over- or mis-diagnosis of both disorders. Movement towards a nosology informed by neurobiology and symptoms, rather than symptoms alone, has the potential to improve the speed and clarity of diagnoses and treatments. To this end, the present study evaluated resting-state functional connectivity (RSFC) in children with primary BD (n=25), primary ADHD (n=24), and typically developing controls (TDCs; n=30) with no history of psychiatric illness. Methods: We enrolled children ages 7-17. Group status was determined via the Child Schedule for Affective Disorders (KSADs-PL). Participants completed an 8-minute RSFC EPI BOLD sequence and a T1 MPRAGE scan. We evaluated RSFC between seeds from the left dorsolateral prefrontal cortex (DLPFC), amygdala, and accumbens areas based on prior research implicating these areas in pediatric BD. Images were analyzed using the CPAC pipeline. Results: Analyses revealed significantly greater RSFC between the (1) left DLPFC and left occipital gyrus proximal to fusiform gyrus and (2) left accumbens area and right superior parietal lobule in TDC vs. BD participants (pairwise comparison ps = .026 and .013, respectively). Conclusions: Data indicate that altered task-independent functional connectivity in the DLPFC and accumbens areas may be specific to pediatric BD. Further study is warranted to determine if this specificity extends to other psychiatric disorders involving irritability, such as anxiety, as a potential biological diagnostic or treatment marker

Stereotyped behaviors are prominent in both the ASD and ID populations; stereotypies can impede social skill acquisition, interfere with learning, and adversely affect an individual's quality of life. The current study explored the effect of cognitive skills and autism spectrum disorder (ASD) on the rate of stereotypies in 2019 children aged 17-39 months. Cognitive abilities were assessed using the cognitive developmental quotient (DQ) on the Battelle Developmental Inventory, Second Edition (BDI-2); two levels of cognitive skill were used: (1) low (cognitive DQ less than or equal to 70), and (2) typical (cognitive DQ greater than 70). Stereotypies were examined utilizing the Baby and Infant Screen for Children with aUtIsm Traits, Part 3 (BISCUIT-Part 3). Children with ASD were found to have greater rates of overall stereotyped behaviors compared to children with atypical development, regardless of cognitive level; however, children with ASD and typical cognitive ability evinced the highest rate of stereotypies. An examination of specific stereotyped behaviors (i.e., unusual play with objects, repeated and unusual vocalizations, repeated and unusual body movements) revealed disparate results. Research and clinical implications regarding these findings are discussed. (C) 2014 Elsevier Ltd. All rights reserved.

Adolescent overweight/obesity (OW/O) has reached epidemic proportions. The Youth Self-Report (YSR) was administered to 514 primarily Hispanic urban high school students to examine the relationship between weight and psychological distress. YSR and study population-specific norms were used to assess risk on Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, and Social Problems scales. OW/O status increased Social Problems regardless of norms. OW/O students endorsed greater Withdrawn/Depressed symptoms with YSR norms; greater Anxious/Depressed and Somatic Complaints were endorsed with population-specific norms. Females drive results. Findings suggest norms need to incorporate minority and economically disadvantaged groups.