Christopher J McDougle

Harvard University, Cambridge, Massachusetts, United States

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Publications (269)1642.26 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Journal of autism and developmental disorders. 09/2014;
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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.
    Autism : the international journal of research and practice. 09/2014;
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    ABSTRACT: Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain.
    Autism 02/2014; · 2.27 Impact Factor
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    ABSTRACT: Abstract Objective: The purpose of this study was to assess change in body mass index (BMI) and age- and gender-adjusted BMI Z-score in subjects ages 2-20 years with autism spectrum disorders (ASD), who were treated longitudinally with risperidone or aripiprazole at a tertiary care ASD clinic. Method: As part of a larger project involving longitudinal drug treatment data in ASD, detailed demographic and treatment data were collected for 142 subjects ages 2-20 years who had been started on risperidone or aripiprazole for treatment of irritability. Mean age at start of treatment, treatment duration, final Clinical Global Impressions-Improvement Scale score, BMI change per year of treatment, and BMI Z-score change per year of treatment (primary outcome measure) were calculated for each drug treatment group. Group means were compared using t tests and Wilcoxon rank sum tests. Results: There was a statistically significant BMI and BMI Z-score increase in the risperidone and aripiprazole treatment groups individually. No statistically significant difference between the two treatment groups was noted in mean BMI change per year of treatment or BMI Z-score change per year of treatment. Conclusions: In our review of long-term naturalistic treatment of irritability using risperidone versus aripiprazole in persons with ASD, a significant increase in both BMI and age- and gender-adjusted BMI Z-score was noted for each treatment group. No significant difference in BMI or BMI Z-score change was noted when the two treatment groups were compared. We conclude that in our patient population at a tertiary care ASD clinic, the effects of risperidone and aripiprazole on body weight gain in naturalistic long-term treatment are no different.
    Journal of child and adolescent psychopharmacology 02/2014; · 2.59 Impact Factor
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    ABSTRACT: Williams syndrome is a relatively rare genetic disorder caused by the hemizygous microdeletion of a region in chromosome 7q11.23. Individuals with Williams syndrome typically present with a highly social, overfriendly, and empathic personality. Comorbid medical and neuropsychiatric disorders are common. Reports of effective pharmacological treatment of associated neuropsychiatric disorders are limited. The authors describe the successful treatment of interfering anger, aggression, and hair-pulling with N-acetylcysteine in a 19-year-old woman with Williams syndrome. The neuropsychiatric symptoms emerged 1 week following an upper gastrointestinal endoscopy, for which fentanyl, midazolam, and propofol were used as anesthetics. The patient's treatment course and hypothesized mechanisms underlying the clinical presentation and symptom resolution are described.
    Journal of child neurology 01/2014; · 1.59 Impact Factor
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    ABSTRACT: A key area of concern in children with autism spectrum disorders (ASDs) are self-injurious behaviors (SIBs). These are behaviors that an individual engages in that may cause physical harm, such as head banging, or self-biting. SIBs are more common in children with ASD than those who are typically developing or have other neurodevelopmental disabilities. Therefore, it is important that clinicians who work with children with ASD have a solid understanding of SIB. The purpose of this paper is to review the research on the epidemiology of SIB in children with ASD, factors that predict the presence of SIB in this population, and the empirically supported behavioral treatments available.
    Psychology Research and Behavior Management 01/2014; 7:125-136.
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    ABSTRACT: This study identified subtypes of aggression in a sample of 206 children with autism spectrum disorder (ASD) who participated in 2 risperidone trials. The narratives were derived from a parent interview about each child's 2 most pressing problems. Five subtypes of aggression emerged: hot aggression only, cold aggression only, self-injurious behavior (SIB) only, aggression and SIB, and nonaggressive. All groups showed a high rate of positive response to risperidone with no differences across subtypes. These study findings extend understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD.
    Child and adolescent psychiatric clinics of North America 01/2014; 23(1):57-72. · 2.88 Impact Factor
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    ABSTRACT: Repetitive behaviors in autism spectrum disorders (ASD) range from motor stereotypy to immersion in restricted interests. The modified Children's Yale-Brown Obsessive Compulsive Scale for children with autism spectrum disorder (CYBOCS-ASD) includes a Symptom Checklist (behavior present or absent) and 5 severity scales (Time Spent, Interference, Distress, Resistance and Control). We assembled CYBOCS-ASD data from 3 Research Units on Pediatric Psychopharmacology Autism Network trials to explore the component structure of repetitive behaviors in children with ASD. Raters trained to reliability conducted the CYBOCS-ASD in 272 medication-free subjects. Fifteen Symptom Checklist items were endorsed for less than 5% of the sample and were dropped. Principal component analysis was used to explore the clustering of 23 checklist items. Component scores computed for each subject were correlated with other measures. We also examined the distribution of severity scales. The subjects (229 boys and 43 girls; mean age = 7.8 ± 2.6 years) met criteria for an ASD; half were intellectually disabled. The PCA resulted in a 5-component solution to classify repetitive behaviors (34.4% of the variance): hoarding and ritualistic behavior; sensory and arranging behavior; sameness and self-injurious behavior; stereotypy; restricted interests. Sensory and arranging and stereotypy components were associated with lower adaptive functioning (Pearson r = 0.2-0.3; p < .003). The resistance scale showed little variation, with more than 60% of the sample with the highest score. Rarely endorsed items can be dropped from the Checklist. The resistance item does not appear to be relevant for children with ASD.
    Journal of the American Academy of Child and Adolescent Psychiatry 01/2014; 53(1):97-107.e1. · 6.97 Impact Factor
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    ABSTRACT: An excitatory/inhibitory (E:I) imbalance marked by enhanced glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of autism spectrum disorders (ASD). We report on the first single-blind placebo lead-in trial of acamprosate, a drug with putative mechanisms restoring E:I imbalance, in twelve youth with ASD. We conducted a 12-week single-blind, placebo lead-in study of acamprosate in youth age 5-17 years with autistic disorder. Six of nine subjects who received active drug treatment were deemed treatment responders (defined by a score at final visit of "very much improved" or "much improved" on the Clinical Global Impressions Improvement scale) and ≥25 % improvement on the Aberrant Behavior Checklist Social Withdrawal subscale. Future larger-scale dose finding studies of acamprosate in ASD may be warranted given this preliminary indication of benefit.
    Journal of Autism and Developmental Disorders 09/2013; · 3.06 Impact Factor
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    ABSTRACT: Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.The Pharmacogenomics Journal advance online publication, 16 July 2013; doi:10.1038/tpj.2013.23.
    The Pharmacogenomics Journal 07/2013; · 5.13 Impact Factor
  • Academic Psychiatry 07/2013; 37(4):288-289. · 0.81 Impact Factor
  • Eric P Hazen, Christopher J McDougle, Fred R Volkmar
    The Journal of Clinical Psychiatry 07/2013; 74(7):739-40. · 5.81 Impact Factor
  • Christopher J McDougle
    Journal of the American Academy of Child and Adolescent Psychiatry 06/2013; 52(6):566-568. · 6.97 Impact Factor
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    ABSTRACT: A Structured Observational Analog Procedure (SOAP), an analogue measure of parent-child interactions, was used to assess treatment outcome in children with Autism Spectrum Disorder and serious behavior problems. It served as a secondary outcome measure in a 24-week, randomized trial of risperidone (MED; N=49) versus risperidone plus parent training (COMB; n=75) (ages 4-13 years). At 24-weeks, there was 28 % reduction in child inappropriate behavior during a Demand Condition (p=.0002) and 12 % increase in compliance to parental requests (p=.004) for the two treatment conditions combined. Parents displayed 64 % greater use of positive reinforcement (p=.001) and fewer repeated requests for compliance (p<.0001). In the analysis of covariance (ANCOVA), COMB parents used significantly more positive reinforcement (p=.01) and fewer restrictive statements (p<.05) than MED parents. The SOAP is sensitive to change in child and parent behavior as a function of risperidone alone and in combination with PMT and can serve as a valuable complement to parent and clinician-based measures.
    Journal of Developmental and Physical Disabilities 06/2013; 25(3):355-371. · 0.89 Impact Factor
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    ABSTRACT: This pilot study explored the efficacy and tolerability of paliperidone augmentation of serotonin reuptake inhibitors (SRIs) in adults with treatment-resistant obsessive-compulsive disorder (OCD). Thirty-four patients aged 24-67 years (mean = 43.7 years, SD = 11.4) who met DSM-IV criteria for OCD and remained symptomatic following 2 or more past adequate SRI trials (including their current medication) were enrolled from May 2008 to March 2012. Participants were treated for 8 weeks in a double-blind study with either paliperidone (up to 9 mg/d) or matching placebo in addition to their SRI. Blinded raters conducted outcome assessments. The primary outcome, obsessive-compulsive symptom severity, was assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcomes included the Clinical Global Impressions-Severity of Illness and -Improvement scales. Paliperidone administration resulted in significant baseline-to-posttreatment reductions in obsessive-compulsive symptoms as measured by the YBOCS (P < .01, d = 0.66), although placebo administration also resulted in medium-sized, trend-level significant YBOCS changes (P = .05, d = 0.53). In exploratory analyses examining between-group differences, tests for paliperidone superiority relative to placebo were not significant (P = .14, d = 0.34); however, a numerical trend toward significant between-group differences was found, with a reduction of 7.98 points on the YBOCS for the paliperidone group compared to a reduction of 4.02 points for the placebo group. Paliperidone was generally well tolerated and not associated with significant weight gain (mean [SD] weight: paliperidone, pretreatment 84.70 [27.08] kg, posttreatment 84.84 [18.99] kg; vs placebo, pretreatment 77.50 [25.33] kg, posttreatment 77.43 [19.90] kg; P = .21). These results suggest that paliperidone augmentation is well tolerated and has potential efficacy in the short-term treatment of some patients with SRI-resistant OCD. Well-powered, randomized, controlled studies are necessary to more definitively address the efficacy of this treatment strategy. identifier: NCT00632229.
    The Journal of Clinical Psychiatry 06/2013; 74(6):e527-e532. · 5.81 Impact Factor
  • Laura C Politte, Christopher J McDougle
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    ABSTRACT: RATIONALE: Autism and related pervasive developmental disorders (PDD) are characterized by impairments in social interaction and communication, restricted interests, and repetitive and stereotyped patterns of behavior. Individuals with PDD frequently display irritability and disruptive behaviors including tantrums, self-injurious behavior, and aggression. Atypical antipsychotics are currently the most efficacious pharmacological interventions available for treatment of irritability associated with PDD. OBJECTIVES: This article aims to review the body of literature pertaining to the use of atypical antipsychotics in the treatment of patients with PDD. METHODS: A PubMed literature search was conducted using the following key words: autism, pervasive developmental disorders, atypical antipsychotics, risperidone, aripiprazole, quetiapine, ziprasidone, olanzapine, clozapine, paliperidone, iloperidone, asenapine, and lurasidone. Search terms were limited to English language, human subjects, and publication from 1999 to present. Relevant references from identified articles were also reviewed. RESULTS: The efficacy and tolerability of risperidone and aripiprazole for the treatment of irritability in autism have been established with multi-site, randomized, controlled trials. Studies supporting the use of other atypical antipsychotics are either limited in scope or less robust in their findings, though newer agents such as ziprasidone and paliperidone show promise. CONCLUSIONS: Atypical antipsychotics are currently first-line pharmacological agents for the treatment of irritability and associated behaviors in children with PDD. Further placebo-controlled studies are warranted to characterize the efficacy and tolerability of the majority of these medications. There is also a need for the development of novel, targeted drugs with more favorable long-term side effect profiles.
    Psychopharmacology 04/2013; · 4.06 Impact Factor
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    ABSTRACT: RATIONALE: Fragile X syndrome (FXS) is an inherited form of developmental disability and a single gene cause of autism. As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts. Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission. METHODS: We conducted a prospective open-label 10-week trial of acamprosate in 12 youth aged 6-17 years (mean age: 11.9 years) with FXS. RESULTS: Acamprosate use (mean dose: 1,054 ± 422 mg/day) was associated with treatment response (defined by a Clinical Global Impressions Improvement (CGI-I) scale score of "very much improved" or "much improved") in nine of 12 (75 %) subjects. Improvement was noted in social behavior and inattention/hyperactivity using multiple standard behavioral outcome measures. No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate. Additionally, pre- and post-treatment blood biomarker analyses looking at brain-derived neurotrophic factor (BDNF) levels found a significant increase in BDNF with treatment. In our pilot sample, treatment response did not correlate with change in BDNF with treatment. CONCLUSIONS: Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention/hyperactivity. The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies. Given these findings, a double-blind, placebo-controlled study of acamprosate in youth with FXS is warranted.
    Psychopharmacology 02/2013; · 4.06 Impact Factor
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    ABSTRACT: This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.
    Journal of Autism and Developmental Disorders 02/2013; · 3.06 Impact Factor
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    ABSTRACT: Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event.
    Translational psychiatry. 01/2013; 3:e274.

Publication Stats

9k Citations
1,642.26 Total Impact Points


  • 2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2013
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2012–2013
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Emory University
      Atlanta, Georgia, United States
    • Massachusetts General Hospital
      • Department of Psychiatry
      Boston, MA, United States
  • 2009–2013
    • University of Pittsburgh
      • Department of Psychiatry
      Pittsburgh, Pennsylvania, United States
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1998–2013
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 1997–2013
    • Indiana University-Purdue University Indianapolis
      • Department of Psychiatry
      Indianapolis, IN, United States
  • 1990–2013
    • Yale University
      • • Child Study Center
      • • Department of Psychiatry
      New Haven, CT, United States
  • 2005–2011
    • Indiana University Bloomington
      Bloomington, Indiana, United States
  • 2010
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 2008–2010
    • The Ohio State University
      • Nisonger Center
      Columbus, Ohio, United States
    • Arizona State University
      • T. Denny Sanford School of Social and Family Dynamics
      Tempe, AZ, United States
  • 2007–2008
    • Indiana University-Purdue University School of Medicine
      • Psychiatry
      Indianapolis, Indiana, United States
    • National Institute of Mental Health (NIMH)
      Maryland, United States
  • 2004
    • Butler Hospital
      Providence, Rhode Island, United States
  • 2002–2004
    • Brown University
      • Department of Psychiatry and Human Behavior
      Providence, RI, United States
  • 1993–2003
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
  • 2000
    • University of Indianapolis
      Indianapolis, Indiana, United States
  • 1997–1998
    • Alpert Medical School - Brown University
      • Department of Psychiatry and Human Behavior
      Providence, RI, United States