Developmental milestones and daily living skills in individuals with Angelman syndrome.

Background: Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz.

Lymphocytic Extracellular Signal-Regulated Kinase Dysregulation in Autism Spectrum Disorder.

Objective: Extracellular signal-regulated kinase (ERK1/2) is a conserved central intracellular signaling cascade involved in many aspects of neuronal development and plasticity. Converging evidence support investigation of ERK1/2 activity in autism spectrum disorder (ASD). We previously reported enhanced baseline lymphocytic ERK1/2 activation in autism, and now we extend our work to investigate the early phase kinetics of lymphocytic ERK1/2 activation in idiopathic ASD.

Recent Advances in the Pharmacological Management of Behavioral Disturbances Associated with Autism Spectrum Disorder in Children and Adolescents.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric condition affecting an estimated one in 36 children. Youth with ASD may have severe behavioral disturbances including irritability, aggression, and hyperactivity. Currently, there are only two medications (risperidone and aripiprazole) approved by the US Food and Drug Administration (FDA) for the treatment of irritability associated with ASD.

Brief Report: Intranasal Ketamine in Adolescents and Young Adults with Autism Spectrum Disorder-Initial Results of a Randomized, Controlled, Crossover, Pilot Study.

Dysregulation of glutamate neurotransmission plays a critical role in autism spectrum disorder (ASD) pathophysiology and is a primary target for core deficit research treatment trials. The mechanism of action of ketamine has striking overlap with the theory of ASD as a disorder of synaptic communication and neuronal networks. This two-dose, double-blind, placebo controlled, cross-over pilot trial of intranasal (IN) ketamine targeting core social impairment included individuals with ASD (N = 21) between 14 and 29 years.

Pediatric Quality of Life Inventory (PedsQL) in Fragile X Syndrome.

To date, health related quality of life (QoL) has not been systematically evaluated in youth with fragile X syndrome (FXS), the most common single gene cause of autism and the most common inherited form of developmental disability. We describe QoL data gathered using the Pediatric Quality of Life Inventory (PedsQL) completed online by 364 parents of youth with FXS. Parents consistently reported across all gender and age groups that their children experienced the highest QoL in Physical functioning and the lowest QoL in Cognitive functioning.

Motor cortex facilitation: a marker of attention deficit hyperactivity disorder co-occurrence in autism spectrum disorder.

The neural correlates distinguishing youth with Autism Spectrum Disorder (ASD-) and ASD with co-occurring Attention Deficit Hyperactivity Disorder (ASD+) are poorly understood despite significant phenotypic and prognostic differences. Paired-pulse transcranial magnetic stimulation (TMS) measures, including intracortical facilitation (ICF), short interval cortical inhibition (SICI), and cortical silent period (CSP) were measured in an age matched cohort of youth with ASD- (n = 20), ASD + (n = 29), and controls (TDC) (n = 24). ASD- and ASD+ groups did not differ by IQ or social functioning; however, ASD+ had significantly higher inattention and hyperactivity ratings.

Pharmacologic Interventions for Irritability, Aggression, Agitation and Self-Injurious Behavior in Fragile X Syndrome: An Initial Cross-Sectional Analysis.

Using a dataset involving 415 individuals with irritability, aggression, agitation and self-injury (IAAS) behaviors from the fragile X syndrome (FXS) FORWARD database, we describe the psychopharmacologic management of IAAS and features of the population of persons with FXS treated with drug therapy for IAAS. Among those with FXS exhibiting IAAS, individuals with FXS receiving drug treatment of IAAS were older, more predominantly male, have more significant intellectual disability, more like to have comorbid autism, hyperarousal, and social impairments. The most commonly utilized medications for IAAS in FXS are antipsychotic medications, specifically aripiprazole and risperidone (37% and 27%, respectively).

Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study.

Background: Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms.

Methods: Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively.

Emotion Regulation Intensive Outpatient Programming: Development, Feasibility, and Acceptability.

Individuals with Autism Spectrum Disorder (ASD) and/or intellectual and developmental disabilities (DD) often struggle with behavior management and emotion-regulation (ER). In this manuscript, we describe the results of a chart review examining a group treatment program designed to address ER deficits in youth with ASD and/or DD. The intensive 5 week program utilizes cognitive behavior, applied behavior analysis, and mindfulness techniques and includes biweekly child and parent groups.

A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder.

Riluzole is a glutamatergic modulator of particular interest in autism spectrum disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled, crossover pilot study we evaluated the safety and tolerability of 5-week of adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period) targeting ASD-associated drug-refractory irritability in eight individuals age 12-25 years.

Sex-Differences in Children Referred for Assessment: An Exploratory Analysis of the Autism Mental Status Exam (AMSE).

The autism mental status exam is an eight-item observational assessment that structures the way we observe and document signs and symptoms of ASD. Investigations of test performance indicate strong sensitivity and specificity using gold-standard assessment as reference standard. This study aims to explore potential sex differences in AMSE test performance and observations of 123 children referred for autism assessment.

Risperidone Treatment for Irritability in Fragile X Syndrome.

Objective: The goal of this study was to assess the effectiveness of risperidone monoantipsychotic therapy targeting irritability in patients with Fragile X syndrome (FXS) in a naturalistic outpatient clinical setting.

Methods: We examined the use of risperidone, predominantly in combination with other nonantipsychotic psychotropic agents, targeting irritability in 21 male patients with FXS with a retrospective analysis of a prospectively collected large developmental disabilities-specific treatment database. Mean age at start of treatment, treatment duration, final dose, body mass index (BMI), and Clinical Global Impressions-Improvement (CGI-I) Scale score at final visit were determined, and changes with treatment were analyzed using paired t-tests.

A randomized controlled trial of levodopa in patients with Angelman syndrome.

Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II.

Eye gaze and pupillary response in Angelman syndrome.

Background: Angelman syndrome (AS) is a rare neurological disorder characterized by severe developmental disability, communication impairment, elevated seizure risk, and motor system abnormalities.

Aims: The aims of this study were to determine the feasibility of social scene eye tracking and pupillometry measures in individuals with AS and to compare the performance of AS participants to individuals with idiopathic Autism Spectrum Disorder (ASD) and typically developing controls (TDC).

Methods And Procedures: Individuals with AS and age- and gender- matched controls completed a social eye tracking paradigm.

Lurasidone for the treatment of irritability and anger in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social interaction and communication as well as restricted patterns of behaviors and interests. Irritability marked by tantrums, self-injury and aggression occurs frequently in youth with ASD, causing significant parent and caregiver distress. Atypical antipsychotics have been the most studied drug class targeting irritability in ASD.

Fragile X targeted pharmacotherapy: lessons learned and future directions.

Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order to manage difficult behaviors, as no drug to date is approved for the treatment of FXS. Drugs impacting a diversity of targets in the brain have been studied in recent FXS-specific clinical trials.

Characterization of Medication Use in a Multicenter Sample of Pediatric Inpatients with Autism Spectrum Disorder.

Nearly 11% of youth with Autism Spectrum Disorder (ASD) undergo psychiatric hospitalization, and 65% are treated with psychotropic medication. Here we characterize psychotropic medication usage in subjects enrolled in the Autism Inpatient Collection. Participant psychotropic medication usage rates topped 90% at admission and discharge, though there was a decline at 2-month follow-up.

Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder.

Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of antipsychotic-induced weight gain in youth with ASD. In this report we assess the long-term impact of metformin on antipsychotic-associated weight gain in a naturalistic sample of 53 youth with ASD.

d-Cycloserine enhances durability of social skills training in autism spectrum disorder.

Background: d-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Here, we assess the impact of DCS 11 weeks following active treatment to evaluate the impact of DCS on treatment response durability.

Brief Report: Diminished Gaze Preference for Dynamic Social Interaction Scenes in Youth with Autism Spectrum Disorders.

In this study, we present an eye-tracking paradigm, adapted from previous work with toddlers, for assessing social-interaction looking preferences in youth ages 5-17 with ASD and typically-developing controls (TDC). Videos of children playing together (Social Scenes, SS) were presented side-by-side with animated geometric shapes (GS). Participants with ASD demonstrated reduced SS preferences compared to TDC, results also represented continuously by associations between higher SS preferences and fewer social difficulties across the combined sample.

Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism.

Background: Dysregulation of extracellular signal-related kinase (ERK) activity has been potentially implicated in the pathophysiology of autistic disorder (autism). ERK is part of a central intracellular signaling cascade responsible for a myriad of cellular functions. ERK is expressed in peripheral blood lymphocytes, and measurement of activated (phosphorylated) lymphocytic ERK is commonly executed in many areas of medicine.

Weight Gain Effects of Second-Generation Antipsychotic Treatment in Autism Spectrum Disorder.

Objective: Irritability (aggression, self-injury, and severe tantrums) associated with autism spectrum disorder (ASD) is often treated with second-generation antipsychotics (SGAs), which are well known for their associated risk of weight gain in youth. Recent reports suggest that youth with ASD treated with SGAs may suffer more pronounced weight gain than typically developing children. In this study, we present a comprehensive comparison of weight gain effects of five SGAs in a clinical population of youth with ASD.

Aggression in autism spectrum disorder: presentation and treatment options.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent difficulties in social communication and social interaction, coupled with restricted, repetitive patterns of behavior or interest. Research indicates that aggression rates may be higher in individuals with ASD compared to those with other developmental disabilities. Aggression is associated with negative outcomes for children with ASD and their caregivers, including decreased quality of life, increased stress levels, and reduced availability of educational and social support.

Analysis of peripheral amyloid precursor protein in Angelman Syndrome.

Angelman Syndrome is a rare neurodevelopmental disorder associated with significant developmental and communication delays, high risk for epilepsy, motor dysfunction, and a characteristic behavioral profile. While Angelman Syndrome is known to be associated with the loss of maternal expression of the ubiquitin-protein ligase E3A gene, the molecular sequelae of this loss remain to be fully understood. Amyloid precursor protein (APP) is involved in neuronal development and APP dysregulation has been implicated in the pathophysiology of other developmental disorders including fragile X syndrome and idiopathic autism.

A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder.

Background: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD.

Methods: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD.