Dataset Information

The Internal Structure of the Aberrant Behavior Checklist Irritability Subscale: Implications for Studies of Irritability in Treatment-Seeking Youth With Autism Spectrum Disorders.

ABSTRACT: Given the prominence of the Aberrant Behavior Checklist (ABC), Irritability Subscale (ABC-I), in treatment outcome studies, we conducted a critical examination of its internal consistency and relationship to other measures of irritability in 758 psychiatrically hospitalized youth with autism spectrum disorder. In exploratory and confirmation samples, we conducted factor and bifactor analyses to describe the internal structure of the ABC-I. Our results suggest that the ABC-I roughly represents a unidimensional construct of irritability, as indicated by a general factor in bifactor analysis. In addition to irritability, subordinate factors are presented that represent tantrums, verbal outbursts, self-harm, and negative affect. Notably, self-harm items explain a large proportion of variance independent of irritability. Therefore, their contribution in analyses of treatment effects should be considered. Further study or revision of the ABC-I may improve convergent validity with transdiagnostic formulations of irritability as well as prevent confound from self-harm in treatment studies for irritability in ASD.

SUBMITTER: Stoddard J

PROVIDER: S-EPMC7080324 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The Internal Structure of the Aberrant Behavior Checklist Irritability Subscale: Implications for Studies of Irritability in Treatment-Seeking Youth With Autism Spectrum Disorders.

Stoddard Joel J Zik Jodi J Mazefsky Carla A CA DeChant Briar B Gabriels Robin R

Behavior therapy 20191126 2

Given the prominence of the Aberrant Behavior Checklist (ABC), Irritability Subscale (ABC-I), in treatment outcome studies, we conducted a critical examination of its internal consistency and relationship to other measures of irritability in 758 psychiatrically hospitalized youth with autism spectrum disorder. In exploratory and confirmation samples, we conducted factor and bifactor analyses to describe the internal structure of the ABC-I. Our results suggest that the ABC-I roughly represents a ...[more]

PMID: 32138940

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Project description:OBJECTIVES:Our clinical experience with low dose loxapine (5-15?mg/day) suggests promising efficacy and safety for irritability in autism spectrum disorders (ASD). We studied low dose loxapine prospectively in adolescents and adults with ASD and irritability. Additionally, we measured loxapine and metabolite concentrations, and brain-derived neurotrophic factor (BDNF) as a biomarker of neuromodulation. METHODS:We performed a 12 week open trial of add-on loxapine in subjects, ages 13-65 years, diagnosed with ASD, and Aberrant Behavior Checklist-Irritability (ABC-I) subscale scores >14. Loxapine was dosed flexibly up to 15?mg daily, starting with 5?mg on alternate days. From weeks 1 to 6, other psychoactive medications were tapered if possible; from weeks 6 to 12, all medication doses were held stable. The primary outcome was the Clinical Global Impressions-Improvement subscale (CGI-I), ratings of Much Improved or Very Much Improved. Secondary outcomes were the ABC-I, Repetitive Behavior Scale-Revised, and Schalock Quality of Life scale. Serum BDNF and loxapine and metabolite concentrations were assayed. BDNF rs6265 was genotyped. RESULTS:Sixteen subjects were enrolled; 12 completed all visits. Median age was 18 years (range 13-39). Median final loxapine dose was 7.5?mg/day (2.5-15). All 14 subjects (100%) with data at week 12 were rated as Much Improved on CGI-I at 12 weeks. Mean change on ABC-I at 12 weeks was -31%, p=0.01. Mean body mass index (BMI)-Z decreased between weeks 6 and 12, p=0.03. Side effects were minimal, and prolactin elevation occurred in only one subject. BDNF concentrations measured in 11 subjects increased significantly (p=0.04). Subjects with AG genotype for BDNF rs6265 required a lower dose of loxapine at study end, but had similar behavioral and BDNF concentration changes as the GG genotype. CONCLUSIONS:Low dose loxapine shows promise as a repurposed drug for irritability in ASD. Loxapine effects on BDNF warrant further study.

Project description:ImportanceMore than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regulating emotional reactions to stimuli has important implications for intervention.ObjectiveTo determine differences in brain responses, habituation, and connectivity during exposure to mildly aversive sensory stimuli in youth with ASDs and SOR compared with youth with ASDs without SOR and compared with typically developing control subjects.Design, setting, and participantsFunctional magnetic resonance imaging was used to examine brain responses and habituation to mildly aversive auditory and tactile stimuli in 19 high-functioning youths with ASDs and 19 age- and IQ-matched, typically developing youths (age range, 9-17 years). Brain activity was related to parents' ratings of children's SOR symptoms. Functional connectivity between the amygdala and orbitofrontal cortex was compared between ASDs subgroups with and without SOR and typically developing controls without SOR. The study dates were March 2012 through February 2014.Main outcomes and measuresRelative increases in blood oxygen level-dependent signal response across the whole brain and within the amygdala during exposure to sensory stimuli compared with fixation, as well as correlation between blood oxygen level-dependent signal change in the amygdala and orbitofrontal cortex.ResultsThe mean age in both groups was 14 years and the majority in both groups (16 of 19 each) were male. Compared with neurotypical control participants, participants with ASDs displayed stronger activation in primary sensory cortices and the amygdala (P < .05, corrected). This activity was positively correlated with SOR symptoms after controlling for anxiety. The ASDs with SOR subgroup had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with groups without SOR. Youth with ASDs without SOR showed a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex (thresholded at z > 1.70, P < .05).Conclusions and relevanceResults demonstrate that youth with ASDs and SOR show sensorilimbic hyperresponsivity to mildly aversive tactile and auditory stimuli, particularly to multiple modalities presented simultaneously, and show that this hyperresponsivity is due to failure to habituate. In addition, findings suggest that a subset of youth with ASDs can regulate their responses through prefrontal downregulation of amygdala activity. Implications for intervention include minimizing exposure to multiple sensory modalities and building coping strategies for regulating emotional response to stimuli.

Dataset Information

The Internal Structure of the Aberrant Behavior Checklist Irritability Subscale: Implications for Studies of Irritability in Treatment-Seeking Youth With Autism Spectrum Disorders.

Publications

The Internal Structure of the Aberrant Behavior Checklist Irritability Subscale: Implications for Studies of Irritability in Treatment-Seeking Youth With Autism Spectrum Disorders.

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