Faculty Bibliography

Background/UNASSIGNED:The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined. Methods/UNASSIGNED:) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined. Results/UNASSIGNED: > .05). Conclusion/UNASSIGNED:Decreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants.

Background/UNASSIGNED:Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods/UNASSIGNED:A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results/UNASSIGNED: = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions/UNASSIGNED:We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration/UNASSIGNED:EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu).

Cogmed Working Memory Training (CWMT), an online cognitive training program developed for children, is an increasingly popular non-pharmacological intervention for ADHD amongst all ages, despite limited supporting evidence. The initial objective of the present work was to examine the short- and long-term impacts of CWMT on brain function in adults with ADHD. However, during the conduct of our study, we experienced multiple levels of failures in recruitment and retention that signaled potential concerns about the suitability of CWMT for adults with ADHD. This perspective piece aims to describe the difficulties we encountered in the context of studies examining the efficacy of CWMT in comparable populations. We trace these difficulties to the limited tolerability of the current CWMT structure for adults with ADHD, and review similar limitations in the literature. We suggest that efficacy of CWMT in children may be due in large part to close monitoring and scaffolding provided by clinicians and caregivers. For CWMT to have viability for widespread use in adults, greater support and structure will be needed for users to improve the likelihood of adherence. We discuss implications and considerations for future efforts in both research and clinical practice.

Serotonin (5-HT) is one of the best-studied modulatory neurotransmitters with ubiquitous presynaptic release and postsynaptic reception. 5-HT has been implicated in a wide variety of brain functions, ranging from autonomic regulation, sensory perception, feeding and motor function to emotional regulation and cognition. The role of this neuromodulator in neuropsychiatric diseases is unquestionable with important neuropsychiatric medications, e.g., most antidepressants, targeting this system. Importantly, 5-HT modulates neurodevelopment and changes in its levels during development can have life-long consequences. In this mini-review, we highlight that exposure to both low and high serotonin levels during the perinatal period can lead to behavioral deficits in adulthood. We focus on three exogenous factors that can change 5-HT levels during the critical perinatal period: dietary tryptophan depletion, exposure to serotonin-selective-reuptake-inhibitors (SSRIs) and poor early life care. We discuss the effects of each of these on behavioral deficits in adulthood.

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n=664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).

Psychiatric disorders are amongst the most prevalent and impairing conditions in childhood and adolescence. Unfortunately, it is well known that general practitioners (GPs) and other frontline health providers (i.e., child protection workers, public health nurses, and pediatricians) are not adequately trained to address these ubiquitous problems (Braddick et al. Child and Adolescent mental health in Europe: infrastructures, policy and programmes, European Communities, 2009; Levav et al. Eur Child Adolesc Psychiatry 13:395-401, 2004). Advances in technology may offer a solution to this problem with clinical decision support systems (CDSS) that are designed to help professionals make sound clinical decisions in real time. This paper offers a systematic review of currently available CDSS for child and adolescent mental health disorders prepared according to the PRISMA-Protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols). Applying strict eligibility criteria, the identified studies (n = 5048) were screened. Ten studies, describing eight original clinical decision support systems for child and adolescent psychiatric disorders, fulfilled inclusion criteria. Based on this systematic review, there appears to be a need for a new, readily available CDSS for child neuropsychiatric disorder which promotes evidence-based, best practices, while enabling consideration of national variation in practices by leveraging data-reuse to generate predictions regarding treatment outcome, addressing a broader cluster of clinical disorders, and targeting frontline practice environments.

Objectives: Temper outbursts are frequently considered symptoms of irritability within the context of ODD, mood disorder, and anxiety disorder. However, even when chronic irritability is not present, they are associated with significant functional impairments. We will provide an overview of our research program that takes a multimodal approach to understanding severe temper outbursts in young children. Methods: We evaluated 216 boys and girls (ages 5-9 years; 73% boys) from diverse socioeconomic backgrounds who comprised three groups: 1) children with severe temper outbursts (STO; n = 80); 2) children with ADHD without outbursts (ADHD; n = 79); and 3) typically developing children (TDC; n = 57). Severe temper outbursts were defined as follows: 1) occurring at least three times per week; 2) lasting >10 minutes; 3) excessive for developmental level; and 4) causing significant impairment. Parents completed a semistructured diagnostic interview about their child and questionnaires about their child's behavior and emotion regulation skills. Children completed brief IQ and language screeners, questionnaires about their emotions and behavior, and tasks assessing frustration tolerance and emotion regulation. A number of these children (64 percent) successfully completed an MRI session that included resting-state, structural, and diffusion tension imaging scans. Results: Approximately 84 percent of the STO group received an ADHD diagnosis, 67 percent were diagnosed with ODD, 28 percent were diagnosed with an anxiety disorder, and 12 percent were diagnosed with a mood disorder. Few exhibited chronic irritabilities based on parent report. On an emotion regulation task, the STO group demonstrated deficits in regulating negative affect in response to frustration. Findings from the resting-state fMRI analyses suggest disruptions in dorsal anterior cingulate cortex (dACC) circuitry associated with tantrum severity. Tantrum severity was also related to cortical thickness of the dACC. Conclusions: Children with severe temper outbursts represent a highly impaired group, even when chronic irritability is not present. Evidence suggests an association between these outbursts and disruptions in dACC circuitry, a region implicated in the expression and regulation of frustration. Such findings have important implications for future conceptualization and treatment of young children with severe temper outbursts

In this pilot study, we examined training effects of a computerized working memory program on resting state functional magnetic resonance imaging (fMRI) measures in children with neurofibromatosis type 1 (NF1). We contrasted pre- with post-training resting state fMRI and cognitive measures from 16 participants (nine males; 11.1 +/- 2.3 years) with NF1 and documented working memory difficulties. Using non-parametric permutation test inference, we found significant regionally specific differences (family-wise error corrected) in two of four voxel-wise resting state measures: fractional amplitude of low frequency fluctuations (indexing peak-to-trough intensity of spontaneous oscillations) and regional homogeneity (indexing local intrinsic synchrony). Some cognitive task improvement was observed as well. These preliminary findings suggest that regionally specific changes in resting state fMRI indices may be associated with treatment-related cognitive amelioration in NF1. Nevertheless, current results must be interpreted with caution pending independent controlled replication.