A potentiated startle study of uncertainty and contextual anxiety in adolescents diagnosed with autism spectrum disorder
Open accessAbstract
Background: Beyond the core symptoms of autism spectrum disorder (ASD), associated symptoms of anxiety can cause substantial impairment for individuals affected by ASD and those who care for them. Methods: We utilized a potentiated startle paradigm with a puff of air to the neck as the unconditioned stimulus in order to investigate differences between response to cued fear and contextual anxiety among cognitively able adolescents diagnosed with ASD and an age- and IQ-matched typically developing group. Results: In a threat-modulated startle paradigm, response patterns to neutral, predictable, and unpredictable conditions were comparable across typically developing and ASD youth in terms of startle response magnitude and latency. However, the ASD group showed significantly greater absolute startle responsivity at baseline and throughout the experiment, suggesting possibly enhanced general sensitivity to threatening contexts. The ASD group, but not the control group, demonstrated moderate to strong negative correlations between psychophysiological response to unpredictable threats (uncertainty) and questionnaire measures of generalized anxiety, intolerance of uncertainty, and repetitive behavior. Conclusions: Our data suggest enhanced general reactivity among the ASD group, possibly reflecting greater sensitivity to the threatening context of the startle paradigm. Associations with the response to uncertainty may help explain shared neurobehavioral mechanisms in ASD and anxiety. This task can provide useful targets for future neuroimaging and genetics studies as well as specific avenues for intervention. We emphasize the importance of further basic and clinical research into links among these important constructs.
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In people with ASD, intolerance of uncertainty is a transdiagnostic construct associated with a range of anxiety disorders.
“Studies of people with ASD suggest that IU is a transdiagnostic construct associated with a range of anxiety disorders [9–13].”
From Coping with Uncertainty in Everyday Situations (CUES©) to address intolerance of uncertainty in autistic children: Study protocol for an intervention feasibility trial (2019) · cites this paper as [12]
The Background section links intolerance of uncertainty (IU) to worry and anxiety in ASD and specifically discusses generalized anxiety disorder. The Results section examines IU alongside total anxiety and GAD symptoms, but the paper does not establish that IU is associated with a range of distinct anxiety disorders in people with ASD or describe it as transdiagnostic. (LLM, conf=0.86)
Experimental — accuracy not yet measuredChamberlain et al. (2013) report associations between shared neurobehavioral mechanisms in ASD and anxiety, indicating specific avenues for intervention targeting IU.
“Chamberlain et al. (2013) report associations between shared neurobehavioral mechanisms in ASD and anxiety, indicating specific avenues for intervention targeting IU, and Maisel et al. (2016) illustrate the role that IU has in anxiety in autistic adults.”
From Towards a Treatment for Intolerance of Uncertainty for Autistic Adults: A Single Case Experimental Design Study. (2018) · cites this paper as Chamberlain et al. 2013
The Discussion reports associations among startle response, intolerance of uncertainty (IU), repetitive behavior, and anxiety symptoms in adolescents with ASD, but says the processes linking them have not been adequately studied. The Conclusions say further research may identify avenues for improved anxiety treatment; they do not identify a specific intervention targeting IU or establish a shared neurobehavioral mechanism. (LLM, conf=0.86)
Experimental — accuracy not yet measuredChamberlain et al. (2013) report associations between shared neurobehavioural mechanisms in ASD and anxiety, indicating specific avenues for intervention targeting IU.
“Chamberlain et al. (2013) report associations between shared neurobehavioural mechanisms in ASD and anxiety, indicating specific avenues for intervention targeting IU.”
From Towards a Treatment for Intolerance of Uncertainty in Young People with Autism Spectrum Disorder: Development of the Coping with Uncertainty in Everyday Situations (CUES©) Programme. (2017) · cites this paper as Chamberlain et al. (2013)
The Discussion reports associations among responses to uncertainty, IU, repetitive behavior, and anxiety symptoms in ASD, but says the underlying pathways need further study. The Conclusions suggest that studying these mechanisms could identify avenues for improved treatment of anxiety-related distress; they do not specify an intervention targeting IU. No page numbers are available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe IUS-12 has been successfully used to show an association between intolerance of uncertainty and anxiety in children and adolescents diagnosed with ASD.
“The IUS-12 has been successfully used to show an association between intolerance of uncertainty and anxiety in children and adolescents diagnosed with ASD (Boulter et al., 2014; Chamberlain et al., 2013).”
From Modeling the cognitive mechanisms linking autism symptoms and anxiety in adults. (2016) · cites this paper as Chamberlain et al., 2013
The Methods (Associated variables; page unavailable) say the study used a shortened 12-item IUS in adolescents with ASD. The Results (Relationship with associated variables; page unavailable) report that child-reported IU and anxiety scores were each associated with startle response during the unpredictable condition, but do not establish a direct association between IU and anxiety scores. The sample was aged 15–18, rather than spanning children and adolescents. (LLM, conf=0.88)
Experimental — accuracy not yet measuredChamberlain et al. reported associations between shared neurobehavioural mechanisms in ASD and anxiety, indicating specific avenues for intervention targeting intolerance of uncertainty.
“Chamberlain et al. [12] reported associations between shared neurobehavioural mechanisms in ASD and anxiety, indicating specific avenues for intervention targeting IU.”
There is a growing evidence base for the centrality of IU to anxiety in autistic people.
“Given the growing evidence base of the centrality of IU to anxiety in autistic people (Boulter et al. 2014; Chamberlain et al. 2013; Rodgers et al. 2016a, b; Keefer et al. 2016; Wigham et al. 2015)”
From Towards a Treatment for Intolerance of Uncertainty for Autistic Adults: A Single Case Experimental Design Study. (2018) · cites this paper as Chamberlain et al. 2013
A potentiated startle study has suggested a role for IU in the physiological arousal responses associated with anxiety.
“a potentiated startle study has suggested a role for IU in the physiological arousal responses that are associated with anxiety (Chamberlain et al., 2013).”
From Modeling the cognitive mechanisms linking autism symptoms and anxiety in adults. (2016) · cites this paper as Chamberlain et al., 2013
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“Multiple studies have now established the link between IU, anxiety, and ASD symptomology (28, 34, 35, 39).”
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Self-citationDefensive activation to (un)predictable interoceptive threat: The NPU respiratory threat test (NPUr)
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Exercise decreases defensive responses to unpredictable, but not predictable, threat
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Dialectical Behavior Therapy in Autism
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Cadherin-16 regulates acoustic sensory gating in zebrafish through endocrine signaling
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Not So Fast: Autistic traits and Anxious Apprehension in Real-World Visual Search Scenarios
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- Authors
- Chamberlain, P. D., Rodgers, J., Crowley, M. J., White, S. E., Freeston, M. H., & South, M.
- Affiliations
- Brigham Young University (US)
- Newcastle University (GB)
- Yale University (US)
- University of California, Davis (US)
- Corresponding author
- South, Mikle
- Venue
- Molecular Autism
- Published
- 2013-09-04
- Volume
- 4
- Issue
- 1
- Pages
- 31-31
- ISSN
- 2040-2392 (ISSN-L)
- PMC
- PMC3844321
- OpenAlex
- W2101682915
- Cited by
- 99
- References
- 41
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 16 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 12 · 2015: 4 · 2014: 5 · 2013: 1
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Autism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Brigham Young University
- National Alliance for Research on Schizophrenia and Depression
- National Institute for Health and Care Research
- Newcastle University
- Fundação Bial
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, adolescents, anxiety, uncertainty, intolerance of uncertainty, generalized anxiety disorder, repetitive behavior, threat sensitivity
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