Christopher J McDougle

Boston Children's Hospital, Boston, Massachusetts, United States

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Publications (342)1772.89 Total impact

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    ABSTRACT: Background: Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. Methods: A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. Results: No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. Conclusions: The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. Trial registration: ClinicalTrials.govNCT01086475.
    Full-text · Article · Dec 2016 · Molecular Autism
  • Logan K Wink · Ernest V Pedapati · Paul S Horn · Christopher J McDougle · Craig A Erickson
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    ABSTRACT: Objective: The purpose of this study was to explore the use of multiple antipsychotic medications in patients with autism spectrum disorder (ASD) by reviewing the longitudinal medication management of 1100 patients consecutively treated for behavioral symptoms associated with ASD at a tertiary care specialty clinic. Methods: We identified all patients with ASD treated with daily doses of two or more antipsychotics for at least two visits at our clinic. For each patient meeting inclusion criteria, diagnostic and demographic data were collected. To evaluate clinical need and effectiveness of antipsychotic medications in this sample, we reviewed symptoms targeted with each antipsychotic medication and concomitant medications prescribed. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scale ratings had been completed at the time of each visit, and the duration of treatment with antipsychotic medications was determined. To evaluate the safety and tolerability of antipsychotic medication use in ASD, we reviewed reported adverse effects and calculated body mass index (BMI) change with treatment. Results: Seventy patients met the inclusion criteria (6.4% of our sample). The majority of patients were moderately to severely ill Caucasian males, as determined by baseline mean CGI-S of 4.7 (SD = 0.8), and were diagnosed with autistic disorder and comorbid intellectual disability. The mean age was 15.1 years (SD = 10.9), the primary targeted symptoms were agitation/irritability, physical aggression, and self-injury. The majority of patients remained on two or more antipsychotics for >1 year. In this population, patients demonstrated greater symptomatic improvement and generally tolerated treatment without significant adverse effects. Conclusions: The use of two or more antipsychotic medications may be increasingly common in patients with ASD. This retrospective study demonstrates that this treatment approach may be of some clinical benefit, and is generally well tolerated. Prospective studies focusing on the efficacy and safety of concomitant antipsychotic medication usage in ASD should be considered.
    No preview · Article · Oct 2015 · Journal of child and adolescent psychopharmacology
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    ABSTRACT: Hyperactivity, impulsiveness, and distractibility are common problems in children with autism spectrum disorder (ASD). Extended-release guanfacine is approved for children with attention deficit hyperactivity disorder but not well studied in ASD. In a multisite, randomized clinical trial, extended-release guanfacine was compared with placebo in children with ASD accompanied by hyperactivity, impulsiveness, and distractibility. Sixty-two subjects (boys, N=53; girls, N=9; mean age=8.5 years [SD=2.25]) were randomly assigned to guanfacine (N=30) or placebo (N=32) for 8 weeks. The guanfacine group showed a 43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale (least squares mean from 34.2 to 19.3) compared with a 13.2% decrease in the placebo group (least squares mean from 34.2 to 29.7; effect size=1.67). The rate of positive response (much improved or very much improved on the Clinical Global Impression-Improvement scale) was 50% (15 of 30) for guanfacine compared with 9.4% (3 of 32) for placebo. A brief cognitive battery tapping working memory and motor planning showed no group differences before or after 8 weeks of treatment. The modal dose of guanfacine at week 8 was 3 mg/day (range: 1-4 mg/day), and the modal dose was 3 mg/day (range: 2-4 mg/day) for placebo. Four guanfacine-treated subjects (13.3%) and four placebo subjects (12.5%) exited the study before week 8. The most common adverse events included drowsiness, fatigue, and decreased appetite. There were no significant changes on ECG in either group. For subjects in the guanfacine group, blood pressure declined in the first 4 weeks, with return nearly to baseline by endpoint (week 8). Pulse rate showed a similar pattern but remained lower than baseline at endpoint. Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD.
    No preview · Article · Aug 2015 · American Journal of Psychiatry
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    ABSTRACT: Previous cross-sectional evidence has linked antipsychotic-related weight gain to reduced body iron concentration. Using longitudinal data, we examined the association between changes in weight following risperidone initiation or discontinuation and ferritin concentration. Study 1: Between April 2004 and September 2007, participants were enrolled from outpatient settings in a prospective randomized clinical trial comparing the efficacy of risperidone monotherapy to the combination of risperidone and behavior therapy in targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old participants in long-term open-label risperidone treatment at study entry returned for follow-up 1.5 years later, between July 2007 and July 2011. Available blood samples were used to measure ferritin. Linear multivariable regression analysis tested the association between ferritin concentration and change in age-sex-specific body mass index (BMI) z score between study entry and endpoint, adjusting for relevant confounders. Study 1 sample consisted of 73 participants (85% males, mean age: 7.7 ± 2.4 years). After 18.0 ± 2.0 weeks on risperidone, their BMI z score increased by 0.93 ± 0.70 points and ferritin concentration declined by 6.8 ± 13.3 μg/L. After adjusting for age and sex, change in BMI z score was inversely correlated with percent change in ferritin concentration (β = -18.3, P < .003). Study 2 participants had all been receiving risperidone at study entry. At follow-up, 1.5 ± 0.3 years later, risperidone was discontinued in 26 of the 96 who were included in the analysis. Neither change in BMI z score nor in ferritin concentration was different between those who continued versus discontinued risperidone. However, a reduction in BMI z score between study entry and follow-up was associated with higher ferritin concentration at follow-up in participants who discontinued risperidone compared to those who continued it (P = .01). Risperidone-related weight gain is associated with a reduction in body iron reserves, which appears to improve with weight loss following risperidone discontinuation. Preliminary evidence suggests that risperidone may also directly inhibit iron absorption. Identifier: NCT00080145. © Copyright 2015 Physicians Postgraduate Press, Inc.
    No preview · Article · Aug 2015 · The Journal of Clinical Psychiatry
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    ABSTRACT: Risperidone has demonstrated efficacy for acute (8 week) and intermediate length (6 month) management of severe irritability and aggression in children and adolescents with autism. Less is known about the long-term effects of risperidone exposure in this population. We examined the tolerability, safety, and therapeutic benefit of risperidone exposure over a 1-2 year follow-up period. In a naturalistic study, 84 children and adolescents 5-17 years of age (from an original sample of 101) were assessed an average of 21.4 months after initial entry into a placebo-controlled 8 week trial of risperidone for children and adolescents with autism and severe irritability. They were assessed at baseline and at follow-up on safety and tolerability measures (blood, urinalysis, electrocardiogram [ECG], medical history, vital signs, neurological symptoms, other adverse events), developmental measures (adaptive behavior, intelligence quotient [IQ]), and standardized rating instruments. Treatment over the follow-up period, after completion of protocol participation, was uncontrolled. Statistical analyses assessed outcome over time with or without prolonged risperidone therapy. Two-thirds of the 84 subjects continued to receive risperidone (mean 2.47 mg/day, S.D. 1.29 mg). At follow-up, risperidone was associated with more enuresis, more excessive appetite, and more weight gain, but not more adverse neurological effects. No clinically significant events were noted on blood counts, chemistries, urinalysis, ECG, or interim medical history. Regardless of drug condition at follow-up, there was considerable improvement in maladaptive behavior compared with baseline, including core symptoms associated with autism. Height and weight gains were elevated with risperidone. Social skills on Vineland Adaptive Behavior Scale (VABS) improved with risperidone. Parent-rated Aberrant Behavior Checklist (ABC) Irritability subscale scores were reduced in those taking risperidone at follow-up. Several other measures of maladaptive behavior (some related to socialization) also showed improved functioning in association with risperidone on the ABC or on the Modified Real Life Rating Scale. Increased appetite, weight gain, and enuresis are risks associated with long-term risperidone. Our data suggest that these risks were balanced by longer-term behavioral and social benefits for many children over 1.8 years of ongoing treatment.
    No preview · Article · Aug 2015 · Journal of child and adolescent psychopharmacology
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    ABSTRACT: Previously, we adapted the Home Situations Questionnaire to measure behavioral non-compliance in everyday settings in children with pervasive developmental disorders. In this study, we further revised this instrument for use in autism spectrum disorder and examined its psychometric properties (referred to as the Home Situations Questionnaire-Autism Spectrum Disorder). To cover a broader range of situations and improve reliability, we prepared seven new items describing situations in which children with autism spectrum disorder might display non-compliance. Parents completed ratings of 242 children with autism spectrum disorder with accompanying disruptive behaviors (ages 4-14 years) participating in one of two randomized clinical trials. Results from an exploratory factor analysis indicated that the Home Situations Questionnaire-Autism Spectrum Disorder consists of two 12-item factors: Socially Inflexible (α = 0.84) and Demand Specific (α = 0.89). One-to-two-week test-retest reliability was statistically significant for all scored items and also for subscale totals. The pattern of correspondence between the Home Situations Questionnaire-Autism Spectrum Disorder and parent-rated problem behavior, clinician-rated repetitive behavior, adaptive behavior, and IQ provided evidence for concurrent and divergent validity of the Home Situations Questionnaire-Autism Spectrum Disorder. Overall, the results suggest that the Home Situations Questionnaire-Autism Spectrum Disorder is an adequate measure for assessing non-compliance in a variety of situations in this population, and use of its two subscales will likely provide a more refined interpretation of ratings. © The Author(s) 2015.
    No preview · Article · Jul 2015 · Autism
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    Kelli Dominick · Logan K Wink · Christopher J McDougle · Craig A Erickson
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    ABSTRACT: The purpose of this study was to assess the impact of ziprasidone monoantipsychotic treatment targeting irritability in a naturalistic outpatient autism spectrum disorder (ASD) clinical setting. We examined the use of ziprasidone, predominantly in combination with other psychotropic agents, targeting irritability in 42 youth with ASD in a large ASD-specific treatment database. Mean age at start of treatment, treatment duration, final dose, body mass index (BMI), BMI Z score, and Clinical Global Impressions-Improvement Scale (CGI-I) score at final visit were determined, and changes with treatment were analyzed using paired t tests. Cardiac corrected QT (QTc) interval data were extracted from electrocardiograms when available. Mean age at start of treatment was 11.8 years. And final mean dose of ziprasidone was 98.7 mg/day or 1.7 mg/kg/day. Seventeen (40%) participants were considered treatment responders based on the CGI-I. No changes in QTc (although only examined in nine participants), weight, BMI, or other vital signs were noted, with ziprasidone use. The rate of treatment response was less than what has been reported for the two atypical antipsychotics, risperidone and aripiprazole, approved by the Food and Drug Administration (FDA) for the treatment of irritability in autistic disorder. The response rate with ziprasidone may be more consistent with response rates for other atypical antipsychotics, although none of these agents has been studied in larger-scale double-blind, placebo-controlled trials. The lower rate of response to ziprasidone in this open-label trial is likely influenced by the treatment-refractory nature of the population studied. The weight neutrality of ziprasidone appears favorable compared with other second generation antipsychotics in this population. The response rate to ziprasidone targeting irritability may be lower than response rates associated with FDA-approved agents for this indication. Overall, ziprasidone use appeared well tolerated in youth with ASD.
    Full-text · Article · Jun 2015 · Journal of child and adolescent psychopharmacology
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    ABSTRACT: The purpose of this chapter is to present results from recent research on social cognition in autism spectrum disorder (ASD). The clinical phenomenology and neuroanatomical circuitry of ASD are first briefly described. The neuropharmacology of social cognition in animal models of ASD and humans is then addressed. Next, preclinical and clinical research on the neurohormone oxytocin is reviewed. This is followed by a presentation of results from preclinical and clinical studies on the excitatory amino acid glutamate. Finally, the role of neuroinflammation in ASD is addressed from the perspectives of preclinical neuroscience and research involving humans with ASD.
    No preview · Article · May 2015 · Handbook of experimental pharmacology
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    ABSTRACT: Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4-17 years). At the medication-free baseline, the internal consistency on the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach's alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all three active treatment groups showed significant improvement (effect sizes: 0.74-0.88). There were no differences between active treatment groups. These results indicate that the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder has acceptable test-retest as evidenced by the medium to high correlations in the placebo group and demonstrated sensitivity to change with treatment. © The Author(s) 2015.
    Full-text · Article · Apr 2015 · Autism
  • Brittany Crowley · Yamini J Howe · Christopher J McDougle

    No preview · Article · Mar 2015 · Journal of Child and Adolescent Psychopharmacology
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    ABSTRACT: This pilot study compared the pharmacologic treatment history and clinical outcomes observed in pediatric outpatients with psychiatric disorders exposed to drugs of abuse in utero to those of an age-matched, sex-matched and psychiatric disorder-matched, non-drug-exposed group. In this matched cohort study, medical records of children treated at an academic, child and adolescent psychiatry outpatient clinic were reviewed. Children with caregiver-reported history of prenatal drug exposure were compared with a non-drug-exposed control group being cared for by the same providers. Patients were rated with the Clinical Global Impressions-Severity scale (CGI-S) throughout treatment. The changes in pre-treatment and post-treatment CGI-S scores and the total number of medication trials were determined between groups. The drug-exposed group (n = 30) had a higher total number of lifetime medication trials compared with the non-drug-exposed group (n = 28) and were taking significantly more total medications, at their final assessment. Unlike the non-drug-exposed group, the drug-exposed group demonstrated a lack of clinical improvement. These results suggest that in utero drug-exposed children may be more treatment-refractory to or experience greater side effects from the pharmacologic treatment of psychiatric disorders than controls, although we cannot determine if early environment or drugs exposure drives these findings. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Mar 2015 · Human Psychopharmacology Clinical and Experimental
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    Laura C. Politte · Yamini Howe · Lisa Nowinski · Michelle Palumbo · Christopher J. McDougle
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    ABSTRACT: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders that manifest in early childhood and persist throughout the lifespan; treatment should reflect the unique challenges for that individual at each developmental stage. In early childhood, treatment should focus on the acquisition of language, play skills, joint attention, and effective communication strategies through intensive behavioral and educational interventions, particularly Applied Behavioral Analysis (ABA). Middle childhood and adolescence presents a time for continued skills acquisition, including development of social skills, peer relationships, and maximizing supports for academic weaknesses. In older adolescence and young adulthood, developing vocational and adaptive living skills to maximize opportunities for independence becomes important. ASD are lifelong disorders, and treatment in adulthood includes ensuring opportunities for social, leisure, and vocational activities, maintaining physical health through diet and exercise, and support for transitions in caregiving as parents age. Throughout the lifespan, clinicians should remain mindful of medical complications that can affect behavior and may not be readily apparent in individuals with limited verbal abilities, including gastrointestinal problems such as reflux and constipation, seizures, and allergies. Current pharmacological interventions are primarily aimed at ameliorating the challenging emotional and behavioral symptoms that accompany ASD rather than the core symptoms of ASD themselves. However, substantial evidence-based research into most medications for ASD is lacking. Two atypical antipsychotics, risperidone and aripiprazole, have indication for the treatment of severe irritability in youths with ASD, though all other medication use in ASD is considered off-label. Behaviorally based therapies, including ABA and cognitive-behavioral therapy (CBT), may be helpful for symptoms of depression, anxiety, and impaired self-regulation. Clinicians should remain mindful that many families will seek out complementary and alternative medicine (CAM) approaches for their child, and appropriate guidance about the safety and efficacy of these interventions should be offered. Drug therapies that directly target the varied neurobiological underpinnings of ASD are an area of great interest for future research and treatment.
    Preview · Article · Mar 2015
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    Nicole R Zürcher · Anisha Bhanot · Christopher J McDougle · Jacob M Hooker
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    ABSTRACT: Non-invasive positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are techniques used to quantify molecular interactions, biological processes and protein concentration and distribution. In the central nervous system, these molecular imaging techniques can provide critical insights into neurotransmitter receptors and their occupancy by neurotransmitters or drugs. In recent years, there has been an increase in the number of studies that have investigated neurotransmitters in autism spectrum disorders (ASD), while earlier studies mostly focused on cerebral blood flow and glucose metabolism. The underlying and contributing mechanisms of ASD are largely undetermined and ASD diagnosis relies on the behavioral phenotype. Discovery of biochemical endophenotypes would represent a milestone in autism research that could potentially lead to ASD subtype stratification and the development of novel therapeutic drugs. This review characterizes the prior use of molecular imaging by PET and SPECT in ASD, addresses methodological challenges and highlights areas of future opportunity for contributions from molecular imaging to understand ASD pathophysiology. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Feb 2015 · Neuroscience & Biobehavioral Reviews
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    ABSTRACT: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain. We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119). TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10(-3)), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10(-3)) and RUPP samples (p = 2.76 × 10(-4)). Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect. Original submitted 20 August 2014; Revision submitted 3 November 2014.
    Full-text · Article · Jan 2015 · Pharmacogenomics
  • Noha F Minshawi · Sarah Hurwitz · Danielle Morriss · Christopher J McDougle
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    ABSTRACT: The objective of this review is to consider the psychological (largely behavioral) and biological [neurochemical, medical (including genetic), and pharmacological] theories and approaches that contribute to current thinking about the etiology and treatment of self-injurious behavior (SIB) in individuals with autism spectrum disorder and/or intellectual disability. Algorithms for the assessment and treatment of SIB in this context, respectively, from a multidisciplinary, integrative perspective are proposed and challenges and opportunities that exist in clinical and research settings are discussed.
    No preview · Article · Nov 2014 · Journal of Autism and Developmental Disorders
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    ABSTRACT: A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immunemodulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD.
    No preview · Article · Nov 2014 · Brain Research
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    ABSTRACT: Peripubertal boys with autism spectrum disorder (ASD) have lower bone mineral density (BMD) than typically developing controls. However, it is not clear whether lower BMD in ASD results in an increased fracture rate. This study examined the rate of fractures in children and adults with and without ASD using a national database of emergency room visits (Nationwide Emergency Department Sample). A higher odds ratio for hip fractures in children and young adults (3-22 years) as well as older adults (23-50 years) with ASD than those without ASD, and a higher odds ratio for forearm and spine fractures in women ages 23-50 with ASD were found. Further studies are necessary to better understand the decreased bone density in ASD and its implications for fracture development.
    No preview · Article · Sep 2014 · Journal of Autism and Developmental Disorders
  • Katherine Bowers · Logan K Wink · Amy Pottenger · Christopher J McDougle · Craig Erickson
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    ABSTRACT: The objective of the study was to characterize the phenotype of males and females with autism spectrum disorder born preterm versus those born at term. Descriptive statistical analyses identified differences between male and female autism spectrum disorder subjects born preterm compared to term for several phenotypic characteristics and comorbidities. Of the 115 (13.0% of 883) born preterm, a greater percentage of males had sleep apnea (13.8% vs 2.5%, p < 0.0001), seizure disorders (17.0% vs 8.5%, p = 0.01), and attention-deficit/hyperactivity disorder (14.9% vs 6.6%, p = 0.005). Females born preterm were more likely to be nonverbal (22.2% vs 4.6%, p = 0.001). In summary, phenotypic differences were observed, especially among males. The results may have implications for understanding the underpinnings of a subset of individuals with autism spectrum disorder and contribute to the development of focused treatments for autism spectrum disorder among children born preterm.
    No preview · Article · Sep 2014 · Autism
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    ABSTRACT: Background: Understanding of the pathophysiology of autism spectrum disorder (ASD) remains limited. Brain overgrowth has been hypothesized to be associated with the development of ASD. A derivative of amyloid-β precursor protein (APP), secreted APPα (sAPPα), has neuroproliferative effects and has been shown to be elevated in the plasma of persons with ASD compared to control subjects. Reduction in sAPPα holds promise as a novel molecular target of treatment in ASD. Research into the neurochemistry of ASD has repeatedly implicated excessive glutamatergic and deficient GABAergic neurotransmission in the disorder. With this in mind, acamprosate, a novel modulator of glutamate and GABA function, has been studied in ASD. No data is available on the impact of glutamate or GABA modulation on sAPPα function. Methods: Plasma APP derivative levels pre- and post-treatment with acamprosate were determined in two pilot studies involving youth with idiopathic and fragile X syndrome (FXS)-associated ASD. We additionally compared baseline APP derivative levels between youth with FXS-associated or idiopathic ASD. Results: Acamprosate use was associated with a significant reduction in plasma sAPP(total) and sAPPα levels but no change occurred in Aβ40 or Aβ42 levels in 15 youth with ASD (mean age: 11.1 years). Youth with FXS-associated ASD (n = 12) showed increased sAPPα processing compared to age-, gender- and IQ-match youth with idiopathic ASD (n = 11). Conclusions: Plasma APP derivative analysis holds promise as a potential biomarker for use in ASD targeted treatment. Reduction in sAPP (total) and sAPPα may be a novel pharmacodynamic property of acamprosate. Future study is required to address limitations of the current study to determine if baseline APP derivative analysis may predict subgroups of persons with idiopathic or FXS-associated ASD who may respond best to acamprosate or to potentially other modulators of glutamate and/or GABA neurotransmission.
    No preview · Article · Aug 2014 · Journal of Psychiatric Research
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    ABSTRACT: Background: No drugs are FDA approved for use targeting the core social impairment of autism and related pervasive developmental disorders (PDDs). Glutamatergic dysregulation is implicated in the pathophysiology of PDDs, now termed ASD. D-Cycloserine (DCS) is FDA approved for the treatment of tuberculosis and the drug is known to impact NMDA glutamate receptor neurotransmission. DCS has been shown to potentiate learning when given prior to therapy sessions in the anxiety disorder literature. Objectives: We evaluated the efficacy of DCS given 30 minutes prior to peer mediated social skills training (SST) in youth aged 5 to 11 years with ASD. Methods: We conducted a double-blind, placebo-controlled trial of low dose (50mg) DCS given prior to manualized SST in 68 children aged 5 to 11 years with ASD over 10 weekly sessions. SST sessions each included 4 youth with ASD and 2 age-matched typically developing peers trainers along with two clinician group facilitators. In addition to evaluating primary and secondary outcome measures after 10 weeks of SST, we additionally conducted a follow up evaluation for each participants 3 months following the SST. Participants with ASD were required to have a full scale IQ greater than 70, meet DSM IV-TR criteria for autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified (PDD-NOS) based upon clinical interview and results from the Autism Diagnostic Interview Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). Our primary outcome measure was the total score on the Social Responsiveness Scale (SRS). Key secondary outcome measures included the Clinical Global Impresisons Improvement (CGI-I) and Severity (CGI-S) scales, the Aberrant Behavior Checklist (ABC), Pediatric Quality of Life Inventory, 4th Edition, and the Vineland-II. We additionally compiled structure observational behavioral data coding with each session to track potential change with treatment throughout the SST. Results: Sixty-eight youth were enrolled in this trial. The results will be available in Spring 2014. Top line results reviewing the primary and key secondary outcome measures will be reported for the drug versus placebo groups in May 2014. Conclusions: Preliminary conclusions will be generated following the dissemination of top line results in May 2014.
    No preview · Conference Paper · May 2014

Publication Stats

16k Citations
1,772.89 Total Impact Points


  • 2015
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2013-2015
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2012-2015
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1991-2015
    • Yale University
      • • Child Study Center
      • • Department of Psychiatry
      New Haven, Connecticut, United States
  • 1985-2015
    • Indiana University-Purdue University Indianapolis
      • • Department of Psychiatry
      • • Department of Pediatrics
      Indianapolis, Indiana, United States
  • 2014
    • Cincinnati Children's Hospital Medical Center
      Cincinnati, Ohio, United States
  • 2012-2014
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1998-2013
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 2007-2012
    • University of Pittsburgh
      • Department of Psychiatry
      Pittsburgh, PA, United States
  • 2006-2012
    • Indiana University School of Medicine
      • Psychiatry
      Indianapolis, Indiana, United States
  • 2001-2012
    • Indiana University Bloomington
      Bloomington, Indiana, United States
    • Indiana University Health
      Bloomington, Indiana, United States
  • 2004
    • Butler Hospital
      Providence, Rhode Island, United States
    • University of Indianapolis
      Indianapolis, Indiana, United States
  • 1993-1996
    • University of New Haven
      New Haven, Connecticut, United States
  • 1991-1995
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
  • 1994
    • Johns Hopkins Medicine
      • Department of Psychiatry and Behavioral Sciences
      Baltimore, Maryland, United States
  • 1992
    • Community Mental Health Consultants, Inc.
      Невада, Missouri, United States