Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

Chugani, Diane C.; Chugani, Harry T.; Wiznitzer, Max; Parikh, Sumit; Evans, Patricia; Hansen, Robin; Nass, Ruth; Janisse, James; Dixon-Thomas, Pamela; Behen, Michael E.; Robert, Richard; Parker, Jacqueline S.; Kumar, Ajay; Muzik, Otto; Edwards, David J.; Hirtz, Deborah

doi:10.1016/j.jpeds.2015.11.033

Cited by 72 publications

(49 citation statements)

References 54 publications

(48 reference statements)

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“…While some have suggested that the female Fmr1 KOs should be included in studies with males based on similarity, here we highlight the marked phenotypic differences, and as such, future research could focus on how these phenotypes could, and should, be treated separately. For instance, repetitive behavior phenotypes are commonly treated using several different types of drugs, including 5‐HT1BR agonists (Ho et al., 2016), 5HT1A partial antagonists (Chugani et al., 2016) and more recently, antioxidants (Hardan et al., 2012). Through the routine exclusion of females from biomedical studies, opportunities are missed to explore potential treatments and how sex may impact the efficacy of such treatments.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Fmr1 results in sex‐specific changes in behavior

et al. 2017

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ObjectiveIn this study, we used a systemic Fmr1 knockout in order to investigate both genotype‐ and sex‐specific differences across multiple measures of sociability, repetitive behaviors, activity levels, anxiety, and fear‐related learning and memory.BackgroundFragile X syndrome is the most common monogenic cause of intellectual disability and autism. Few studies to date have examined sex differences in a mouse model of Fragile X syndrome, though clinical data support the idea of differences in both overall prevalence and phenotype between the sexes.MethodsUsing wild‐type and systemic homozygous Fmr1 knockout mice, we assessed a variety of behavioral paradigms in adult animals, including the open field test, elevated plus maze, nose‐poke assay, accelerating rotarod, social partition task, three‐chambered social task, and two different fear conditioning paradigms. Tests were ordered such that the most invasive tests were performed last in the sequence, and testing paradigms for similar behaviors were performed in separate cohorts to minimize testing effects.ResultsOur results indicate several sex‐specific changes in Fmr1 knockout mice, including male‐specific increases in activity levels, and female‐specific increases in repetitive behaviors on both the nose‐poke assay and motor coordination on the accelerating rotarod task. The results also indicated that Fmr1 deletion results in deficits in fear learning and memory across both sexes, and no changes in social behavior across two tasks.ConclusionThese findings highlight the importance of including female subjects in preclinical studies, as simply studying the impact of genetic mutations in males does not yield a complete picture of the phenotype. Further research should explore these marked phenotypic differences among the sexes. Moreover, given that treatment strategies are typically equivalent between the sexes, the results highlight a potential need for sex‐specific therapeutics.

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Section: Discussionmentioning

confidence: 99%

Deletion of Fmr1 results in sex‐specific changes in behavior

et al. 2017

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“…For instance, mice lacking brain 5-HT, in addition to several abnormal phenotypes (growth retardation, high aggressive behavior, maternal neglect), show selective deficits resembling ASD's symptoms, including impairments in social interactions and repetitive behavior [3,4]. Various pharmacological studies are providing evidence that targeting 5-HTRs has the potential to treat the core symptoms of ASD and associated intellectual disabilities [91][92][93][94]. Recent evidence in animal models suggest that, among other subtypes, the 5-HT7R might be one of the players involved in ASD (see below).…”

Section: The 5-ht7r and Neurological Diseasesmentioning

confidence: 99%

Role of the Serotonin Receptor 7 in Brain Plasticity: From Development to Disease

Crispino

Volpicelli

Perrone-Capano

2019

Preprint

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Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

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“…A recent Autism Speaks sponsored working group panel recommended the Vineland‐II as suitable (having adequate reliability, validity, and responsiveness) to quantify social communication deficits in clinical trials of ASD [Anagnostou et al, ; see also McConachie et al, ]. The Vineland‐II is also increasingly used in randomized trials targeting core ASD symptoms and/or adaptive behavior more broadly [e.g., Chugani et al, ; Dawson et al, ; Hardan et al, ; Scahill et al, ; Umbricht et al, ; Veenstra‐VanderWeele et al, ; Ventola et al, ], in part due to the relative lack of other reliable measures of change in these behaviors [Anagnostou et al, ]. This increasing use may also reflect the relatively broader scope of adaptive behaviors assessed by Vineland‐II, relative to the more circumscribed set of core ASD symptoms (McDougall et al, in press).…”

Section: Introductionmentioning

confidence: 99%

Adaptive behavior in autism: Minimal clinically important differences on the Vineland‐II

et al. 2017

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The Vineland Adaptive Behavior Scales (2nd edition; Vineland-II) is the most widely used scale for assessing day-to-day "adaptive" skills. Yet, it is unknown how much Vineland-II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2-3.75 points on the Vineland-II Composite score represent the "minimal clinically-important difference." These estimates will help evaluate the benefits of potential new treatments for ASD.

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Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

Abstract: ClinicalTrials.gov: NCT00873509.

Cited by 72 publications

References 54 publications

Deletion of Fmr1 results in sex‐specific changes in behavior

Deletion of Fmr1 results in sex‐specific changes in behavior

Role of the Serotonin Receptor 7 in Brain Plasticity: From Development to Disease

Adaptive behavior in autism: Minimal clinically important differences on the Vineland‐II

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