Psychopharmacologic Interventions for Repetitive Behaviors in Autism Spectrum Disorders

Soorya, Latha; Kiarashi, Jessica; Hollander, Eric

doi:10.1016/j.chc.2008.06.003

Cited by 54 publications

(41 citation statements)

References 64 publications

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“…In knock-in mice with a trypotophan hydroxylase 2 mutation that reduces brain serotonin levels, Gsk3β genetic reduction and inhibition by thiadiazolidinone reversed behavioral abnormalities in anxiety-like and social interaction paradigms (Beaulieu et al , 2008). In clinical studies, selective serotonin reuptake inhibitors (SSRIs), including fluoxetine and citalopram, have produced some therapeutic improvements when targeted to various symptoms (Hollander et al , 2000; Hollander et al , 2005; Kolevzon et al , 2006; Parikh et al , 2008; Soorya et al , 2008). However, a more recent multicenter citalopram trial failed to detect significant behavioral improvements, and reported some adverse effects in children (King et al , 2009; Volkmar, 2009).…”

Section: Introductionmentioning

confidence: 99%

Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP

Silverman

Tolu

Barkan

et al. 2009

Neuropsychopharmacol

382

360

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Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including well-replicated deficits in reciprocal social interactions and social approach, unusual patterns of ultrasonic vocalization, and high levels of repetitive self-grooming. These phenotypes offer straightforward behavioral assays for translational investigations of pharmacological compounds. Two proposed treatments for autism were evaluated in the BTBR mouse model. Methyl-6-phenylethynyl-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, blocks aberrant phenotypes in the Fmr1 mouse model of Fragile X, a comorbid neurodevelopmental disorder with autistic features. Risperidone has been approved by the United States Food and Drug Administration for the treatment of irritability, tantrums and self-injurious behavior in autistic individuals. We evaluated the actions of MPEP and risperidone on two BTBR phenotypes, low sociability and high repetitive self-grooming. Open field activity served as an independent control for non-social exploratory activity and motor functions. C57BL/6J (B6), an inbred strain with high sociability and low self-grooming, served as the strain control. MPEP significantly reduced repetitive self-grooming in BTBR, at doses that had no sedating effects on open field activity. Risperidone reduced repetitive self-grooming in BTBR, but only at doses that induced sedation in both strains. No overall improvements in sociability were detected in BTBR following treatment with either MPEP or risperidone. Our findings suggest that antagonists of mGluR5 receptors may have selective therapeutic efficacy in treating repetitive behaviors in autism.

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Section: Introductionmentioning

confidence: 99%

Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP

Silverman

Tolu

Barkan

et al. 2009

Neuropsychopharmacol

382

360

View full text Add to dashboard Cite

show abstract

“…RRBs have been directly targeted as a primary outcome within pharmacological trials (Carrasco, Volkmar, & Bloch, 2012; Soorya, Kiarashi, & Hollander, 2008; King et al, 2009), but with inconsistent results and notable adverse effects. Focused behaviorally-based intervention strategies based on principles of Applied Behavioral Analysis (ABA) have shown reductions in some lower-order sensory-oriented and repetitive behaviors (Kuhn, Hardesty, & Sweeney, 2009; Rapp & Vollmer, 2005; see Boyd, McDonough, & Bodfish, 2012; Harrop, Gulsrud, Shih, Hovsepyan, & Kasari, 2015 for comprehensive reviews).…”

mentioning

confidence: 99%

Brief Report: Reduced Restricted and Repetitive Behaviors after Pivotal Response Treatment

Ventola

Yang

Abdullahi

et al. 2016

J Autism Dev Disord

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Children with ASD show high frequency of restricted and repetitive behaviors (RRBs); however, higher-order RRBs, such as restricted interests, have remained largely resistant to treatment. This study evaluated change in severity of RRBs following a 16-week open trial of Pivotal Response Treatment (PRT). Participants included 15 children with ASD ages 4 to 7 years. RRBs, as measured by the Repetitive Behavioral Scales- Revised (RBS-R) and Aberrant Behaviors Checklist (ABC), decreased significantly after treatment. These reductions remained significant after controlling for change in social communication skills. PRT shows promise in reducing RRBs; although PRT explicitly addresses pivotal social communication skills, there is a secondary and less direct effect on RRBs.

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“…Many children with ASD have clinical symptoms, such as obsessive-compulsive disorder and anxiety, that are seen in other disorders where serotonin deficiency has been implicated,17 and dysfunction in the serotonin system in ASD has been documented by investigators 13. However, response of children with ASD to selective-serotonin reuptake inhibitors is mixed across studies18, 19, 20 and research suggests that at least a subgroup of children with ASD have elevations in serotonin levels 21. Children with ASD have a high rate of executive function problems, inattention, and hyperactivity, all symptoms suggesting dopamine and norepinephrine deficits 22–24.…”

Section: Evidence For Tetrahydrobiopterin Depletion In Autism Specmentioning

confidence: 99%

Tetrahydrobiopterin as a Novel Therapeutic Intervention for Autism

2010

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Summary:Tetrahydrobiopterin (BH 4 ) is an essential cofactor for several critical metabolic pathways that have been reported to be abnormal in autism spectrum disorder (ASD). In addition, the cerebrospinal fluid concentration of BH 4 is reported to be depressed in children with ASD. Over the past 25 years, several clinical trials have suggested that treatment with BH 4 improves ASD symptomatology in some individuals. Two ongoing clinical protocols may help further define the efficacy of BH 4 treatment in children with ASD. First, children with ASD who had low concentrations of cerebrospinal fluid or urine pterins were treated in an open-label manner with 20 mg/kg per day of BH 4 . The majority of children (63%) responded positively to treatment, with minimal adverse events (AEs). Second, a double-blind placebo-controlled study examining the efficacy of 20 mg/kg per day of BH 4 treatment in children with ASD is currently underway. Safety studies from the commercially available forms of BH 4 document the low incidence of AEs, particularly serious AEs. Studies have also documented the ability of BH 4 to cross the blood-brain barrier. Based on the importance of BH 4 in neurodevelopmental metabolic pathways, the safety of BH 4 treatment, and the evidence for a therapeutic benefit of BH 4 treatment in children with ASD, we conclude that BH 4 represents a novel therapy for ASD, one that may gain wider use after further clinical studies have established efficacy and treatment guidelines.

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Psychopharmacologic Interventions for Repetitive Behaviors in Autism Spectrum Disorders

Cited by 54 publications

References 64 publications

Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP

Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP

Brief Report: Reduced Restricted and Repetitive Behaviors after Pivotal Response Treatment

Tetrahydrobiopterin as a Novel Therapeutic Intervention for Autism

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