Aripiprazole decreases irritability in 12 out of 14 youth with autism spectrum disorders.
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ABSTRACT:
SUBMITTER: Maloney A
PROVIDER: S-EPMC4137505 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
Publications
Aripiprazole decreases irritability in 12 out of 14 youth with autism spectrum disorders.
Maloney Ann A Mick Eric O EO Frazier Jean J
Journal of child and adolescent psychopharmacology 20140514 6
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Project description: Not available
| S-EPMC7120220 | biostudies-literature
Project description: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.
| S-EPMC7080324 | biostudies-literature
Project description:BackgroundIrritability in people with autism spectrum disorders (ASD) is common and impairing, yet its mechanisms remain understudied. We investigated symptom reporting and mechanisms of irritability in ASD, focusing on the relation between irritability and physiological stress responses.MethodsForty-seven unmedicated boys with high-functioning ASD (hfASD) and 23 typically developing boys aged 10-16 years completed a psychosocial stress test. Changes in cortisol, heart rate and heart rate variability throughout the test were recorded. Self- and parent-reported measures of irritability were obtained. Irritability symptom reporting in the hfASD group was compared to two groups of boys without ASD: highly irritable boys (severe mood dysregulation, SMD; n = 40) and healthy-control boys (HC; n = 30).ResultsBoys with hfASD scored significantly higher on irritability than HC boys, and they reported a pattern of irritability symptoms closely resembling that of boys with SMD. The internal consistency of irritability in hfASD was high by parent- and self-report. Although boys with hfASD showed significant stress-induced changes in cortisol and heart rate, those who rated themselves as highly irritable had lower cortisol levels throughout the test compared to those low on irritability. Participants rated as highly irritable by their parents showed blunted cortisol and heart rate responses to stress. The effects of irritability on heart rate, but not cortisol, were accounted for by trait anxiety.ConclusionsIrritability can be measured reliably in hfASD and is associated with distinct biological responses to stress.
| S-EPMC4737220 | biostudies-literature
Project description:Anxiety is one of the most common co-occurring psychiatric conditions in youth with autism spectrum disorders (ASDs). This article reviews recent evidence as well as earlier relevant studies regarding the characteristics, assessment, and treatment of anxiety in youth with ASD.It is well established that the prevalence of anxiety in youth with an ASD is significantly greater than the prevalence of anxiety in the general population. Recent studies have highlighted the importance of informant, method, and instrument when measuring anxiety in this population. Despite the high prevalence, findings to date have been unable to identify any consistent risk factors for anxiety. New psychological treatments, including modified cognitive behavioral therapy for youth with high functioning ASD and co-occurring anxiety, are emerging. Pharmacological data, however, are scant. Existing studies show that youth with ASD are at increased risk for behavioral activation when taking SSRIs.Clinicians working with youth with ASD are encouraged to routinely screen for anxiety. Until further data are available, clinical judgment is needed when prescribing treatments, particularly selective serotonin reuptake inhibitors, which require close monitoring of side-effects. Research on risk factors, pathophysiology, and treatment of this condition is needed.
| S-EPMC5764108 | biostudies-other
Project description:Anxiety disorders are one of the most common psychiatric comorbidities among children and adolescents with autism spectrum disorders (ASD). There has been a recent proliferation of research examining the prevalence, phenomenology, assessment and treatment of anxiety disorders among youth with ASD. While there is currently very limited support for the use of pharmacological agents to treat anxiety among youth with ASD and comorbid anxiety, there has been overwhelming support across numerous modestly sized controlled studies for the efficacy of cognitive behavioral therapy. This review discusses advances in the treatment literature for anxiety in youth with ASD, and discusses the current evidence base for whether standard treatment needs to be adapted for this population.
| S-EPMC4886863 | biostudies-other
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.
| S-EPMC4442591 | biostudies-literature
Project description:Autism spectrum disorders (ASD) and early-onset psychosis (EOP) are neurodevelopmental disorders that share genetic, clinical and cognitive facets; it is unclear if these disorders also share spatially overlapping cortical thickness (CT) and surface area (SA) abnormalities. MRI scans of 30 ASD, 29 patients with early-onset first-episode psychosis (EO-FEP) and 26 typically developing controls (TD) (age range 10-18 years) were analyzed by the FreeSurfer suite to calculate vertex-wise estimates of CT, SA, and cortical volume. Two publicly available datasets of ASD and EOP (age range 7-18 years and 5-17 years, respectively) were used for replication analysis. ASD and EO-FEP had spatially overlapping areas of cortical thinning and reduced SA in the bilateral insula (all p's < .00002); 37% of all left insular vertices presenting with significant cortical thinning and 20% (left insula) and 61% (right insula) of insular vertices displaying decreased SA overlapped across both disorders. In both disorders, SA deficits contributed more to cortical volume decreases than reductions in CT did. This finding, as well as the novel finding of an absence of spatial overlap (for ASD) or marginal overlap (for EOP) of deficits in CT and SA, was replicated in the two nonoverlapping independent samples. The insula appears to be a region with transdiagnostic vulnerability for deficits in CT and SA. The finding of nonexistent or small spatial overlap between CT and SA deficits in young people with ASD and psychosis may point to the involvement of common aberrant early neurodevelopmental mechanisms in their pathophysiology.
| S-EPMC6865706 | biostudies-literature
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.
| S-EPMC4861140 | biostudies-literature
Project description:In this study, whole genome sequencing was performed in two autistic families (as trio).
| PRJEB34754 | ENA
Project description:We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents (6-17 years) with autism spectrum disorder (ASD) in a randomized, double-blind, placebo-controlled 8-week study in Japan. Patients received flexibly dosed aripiprazole (1-15 mg/day) or placebo. Ninety-two patients were randomized to placebo (n = 45) or aripiprazole (n = 47). Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8. Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8. All patients randomized to aripiprazole completed the study, and no serious adverse events were reported. Three patients in placebo group discontinued. Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents.
| S-EPMC5617873 | biostudies-literature