Person: McDougle, Christopher
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McDougle
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Christopher
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McDougle, Christopher
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Publication The association between self-injurious behaviors and autism spectrum disorders(Dove Medical Press, 2014) Minshawi, Noha F; Hurwitz, Sarah; Fodstad, Jill C; Biebl, Sara; Morriss, Danielle H; McDougle, ChristopherA 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.Publication A randomized, placebo-controlled trial of d-cycloserine for the enhancement of social skills training in autism spectrum disorders(BioMed Central, 2016) Minshawi, Noha F.; Wink, Logan K.; Shaffer, Rebecca; Plawecki, Martin H.; Posey, David J.; Liu, Hai; Hurwitz, Sarah; McDougle, Christopher; Swiezy, Naomi B.; Erickson, Craig A.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.govNCT01086475Publication A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder(BioMed Central, 2016) Wink, Logan K.; Adams, Ryan; Wang, Zemin; Klaunig, James E.; Plawecki, Martin H.; Posey, David J.; McDougle, Christopher; Erickson, Craig A.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. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing ≥15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. Results: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p < 0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). Conclusions: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. Trial registration Clinicaltrails.gov NCT00453180Publication d-Cycloserine enhances durability of social skills training in autism spectrum disorder(BioMed Central, 2017) Wink, Logan K.; Minshawi, Noha F.; Shaffer, Rebecca C.; Plawecki, Martin H.; Posey, David J.; Horn, Paul S.; Adams, Ryan; Pedapati, Ernest V.; Schaefer, Tori L.; McDougle, Christopher; Swiezy, Naomi B.; Erickson, Craig A.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. Methods: Study participants included 60 outpatient youth with ASD, ages 5–11 years, all with IQ above 70, and significantly impaired social functioning who completed a 10-week active treatment phase during which they received weekly single doses of 50 mg of DCS or placebo administered 30 min prior to group social skills training. Following the 10-week active treatment phase, blinded follow-up assessments occurred at week 11 and week 22. The primary outcome measure for our durability of treatment evaluation was the parent-rated social responsiveness scale (SRS) total raw score at week 22. Results: Analysis of the SRS total raw score demonstrated significant decrease for the DCS group compared to the placebo group (p = 0.042) indicating greater maintenance of treatment effect in the DCS group. DCS was well tolerated, with irritability being the most frequently reported adverse effect in both groups. Conclusions: The findings of this study suggest that DCS may help youth with ASD to maintain skills gained during sort-term social skills training. Larger-scale studies with longer follow-up will be necessary to further understand the long-term impact of DCS paired with structured social skills training. Trial registration ClinicalTrials.gov, NCT01086475