Behaviors Associated With Fever in Children With Autism Spectrum Disorders

Curran, Laura Kresch; Newschaffer, Craig J.; Lee, Li Ching; Crawford, Stephen O.; Johnston, Michael V.; Zimmerman, Andrew W.

doi:10.1542/peds.2007-0360

Cited by 135 publications

(108 citation statements)

References 18 publications

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Section: Significancementioning

confidence: 69%

“…Fourth, widespread anecdotal reports have suggested that fever can dramatically but temporarily ameliorate the disturbed behavior of many autistic patients (21). Notably, the degree of improvement (mostly in stereotypic behavior and inappropriate speech) was unrelated to the severity of fever or of autism (21).…”

Section: Significancementioning

confidence: 96%

“…Notably, the degree of improvement (mostly in stereotypic behavior and inappropriate speech) was unrelated to the severity of fever or of autism (21). This study explicitly suggested that elucidation of the fever response might provide insight into the mechanisms of ASD and point to new therapeutic approaches (21,22). Fever up-regulates heat-shock proteins and related mechanisms central to multiple cellular processes in the CNS, including synaptic transmission (23,24), and may improve long-range cerebral cortical connectivity that is depressed in ASD (25).…”

Section: Significancementioning

confidence: 98%

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Sulforaphane treatment of autism spectrum disorder (ASD)

Singh

Connors

Macklin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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372

261

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Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medicoeconomic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)-derived from broccoli sprout extracts-or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 μmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015-0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.

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Section: Significancementioning

confidence: 69%

Section: Significancementioning

confidence: 96%

Section: Significancementioning

confidence: 98%

See 1 more Smart Citation

Sulforaphane treatment of autism spectrum disorder (ASD)

Singh

Connors

Macklin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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372

261

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“…Following is Dr. Kinsbourne's response. Curran et al (2007) confirmed that children with autism behave less aberrantly when they are febrile due to infections, a phenomenon that might offer insight into the cause and treatment of autistic symptoms. Good (2011) attributes the improvement to an increase in cerebral blood flow.…”

mentioning

confidence: 69%

“…Evidence is lacking that fever increases the perfusion of these regions, or that they would function better if it did. Indeed, Curran et al (2007) found no relationship between degree of fever and degree of improvement.…”

mentioning

confidence: 94%

The Immune System’s Moderating Response to Inflammation Relieves Autistic Behavior: Response to Peter Good

Kinsbourne

2011

Neuropsychol Rev

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Children with autism spectrum disorder who improve with fever: Insights from the Simons Simplex Collection

et al. 2017

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Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show parent-reported behavioral improvements associated with fever and (b) compare the demographic, behavioral, and genetic characteristics of this subset of children to children whose parents report no change during fever. Parents of 2,152 children from the Simons Simplex Collection provided information about whether and in which areas their child improved during fever. Children were randomly assigned into discovery or replication samples. In discovery analyses, children who reportedly improved with fever (Improve Group) were compared to those who reportedly did not improve (No Improve Group) on demographics, medical history, ASD symptoms, adaptive skills, and presence of de novo ASD-associated mutations. Significant and marginal results from discovery analyses were tested in the replication sample. Parent reports of 17% of children indicated improvements during fever across a range of domains. Discovery and replication analyses revealed that the Improve Group had significantly lower non-verbal cognitive skills (NVIQ) and language levels and more repetitive behaviors. Groups did not differ on demographic variables, parentreport of current ASD symptoms or the presence of de novo mutations. Understanding the profiles of children who improve during episodes of fever may provide insights into innovative treatments for ASD. Autism Res 2018, 11: 175-184. V C 2017 International Society for Autism Research, Wiley Periodicals, Inc.Lay Summary: This study explored characteristics of children with ASD who are reported to improve during fever.Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non-verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD.

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Behaviors Associated With Fever in Children With Autism Spectrum Disorders

Cited by 135 publications

References 18 publications

Sulforaphane treatment of autism spectrum disorder (ASD)

Sulforaphane treatment of autism spectrum disorder (ASD)

The Immune System’s Moderating Response to Inflammation Relieves Autistic Behavior: Response to Peter Good

Children with autism spectrum disorder who improve with fever: Insights from the Simons Simplex Collection

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