Marina Sarris
Interactive Autism Network at Kennedy Krieger Institute
Date Published: September 26, 2017
A fever usually makes you feel foggy, tired, and grumpy. But in some children with autism, a fever makes them "better," that is, more social, alert, even chatty. As one mother described it, her child's fevers provide a glimpse into what her child might be like without autism.
Researchers have wondered about the so-called "fever effect" since at least 1980, when a viral infection swept through a therapeutic nursery for children with autism at Bellevue Psychiatric Hospital in New York. Hospital staff reported that the children were more social, alert, and talkative while feverish.1 When their fevers faded, so did those behavioral improvements. Researchers wonder what this curious phenomenon can tell us about the mechanics of autism – and about possible treatments.
Unraveling the fever effect could lead to "innovative ways to improve the lives of individuals affected by autism," explained Rebecca Grzadzinski, a graduate student working with autism expert Catherine Lord PhD. In a new study, a research team including Ms. Grzadzinski and Dr. Lord described the characteristics of youth who are most likely to experience the fever effect. The team examined data from 2,152 children with autism who participated in the Simons Simplex Collection research project. Parents of 362 children, or 17 percent, reported that their sons or daughters had experienced the fever effect. As a group, those children also had lower nonverbal cognitive skills, less language, and more repetitive behaviors than the children who did not experience the fever effect.2
Finding a Different Child When Fever Strikes
She would say, 'Will you watch my favorite TV show with me,' 'I love you Mommy,' and 'Thank you, Mommy.'
Connie Sproul Bonarigo said her daughter with autism would act like a different person when she had a fever. Her daughter was prone to frequent outbursts and tantrums when well, but she became calm, easy-going, and affectionate when ill. "It was almost as if someone had given her a sedative," said Ms. Bonarigo, of New Jersey. "She was so loving and affectionate. She would say, 'Will you watch my favorite TV show with me,' 'I love you Mommy,' and 'Thank you, Mommy.' This would go on until the fever would go down." Her daughter is now a young adult, and still becomes more agreeable when feverish, said Ms. Bonarigo, a member of the advisory council for the Interactive Autism Network.
A mother from Texas described a similar experience when her son with autism, who is now 17, was younger. "When he didn't have a fever, he was hyperactive, stimming, pacing and running," Haven DeLay said. (Stims are lay shorthand for self-stimulatory behaviors, such as rocking, finger-flicking, and other repetitive behaviors that are common to autism). Ms. DeLay continued, "His verbal stimming was off the charts. When he had a fever, all of that stopped. There was no stimming, no tremors, no tics; every behavioral thing was better. Antibiotics helped him, too."
Researchers do not know why the fever effect appears to be more common in children with significant repetitive behaviors and other symptoms. Those children may have brain differences that make them susceptible to the fever effect. Or, the study also said, "It is possible that behavioral changes during fever are simply more easily noticeable in children who have more prominent repetitive behaviors."2
Earlier autism research suggested that more children with autism experience the fever effect than the 17 percent found in the SSC study. A small study by researchers in Baltimore found that as many as 80 percent of children with autism experienced a fever effect.3 In that 2007 research, parents of 103 children were asked to take their child's temperature and rate their behavior during and after a fever of at least 100.4 degrees Fahrenheit (38.0 degrees Celsius). Thirty children developed a fever during the study; they were compared to similar children who were fever-free. The researchers found that 25 of the 30 feverish children had fewer abnormal behaviors during fever, including irritability, hyperactivity, repetitive motions (such as hand flapping), and inappropriate speech. Those changes disappeared after the fever ended.3
Could the Fever Effect Occur Along a Spectrum?
One of those researchers, neurologist Andrew W. Zimmerman, discussed the study in an article for Autism Speaks. "This finding – that the vast majority of children with autism experience behavioral improvements during fever – suggests that the fever effect may be far more common than anyone realized. Perhaps parents don't detect improvement in autism symptoms below a certain threshold. This may be because illness tends to hide the improvements. Or, as in many areas of biology, I suspect there is a wide range of effects – from barely detectable to striking. The more-dramatic responses will be more likely to prompt parents to report and seek to understand the behavioral improvement."4
Skeptics may wonder if behavior changes are simply due to the fatigue that people feel when feverish. But researchers say something else is likely at work in the children who experience the fever effect. Dr. Zimmerman's team had asked parents to rate lethargy and behavior during and after fevers. The researchers found that improvements in behavior did not depend on how tired children appeared to be when ill.3
"We have a lot of evidence that individuals with autism think differently and that their brain functions in a different way. So why would we rule out the possibility that maybe fever impacts individuals with autism differently?" Ms. Grzadzinski said.
What Might Cause The Fever Effect in Autism?
What could be happening to those children when their temperatures rise? "The short answer is, we don't know," Ms. Grzadzinski said. But the longer answer is that fever may cause temporary cellular or metabolic changes that affect the central nervous system, she said. Those changes, in turn, affect behavior. Possible explanations include changes to the action of cells in the brain's hypothalamus5 or to the release of glutamine or taurine.6 Another theory involves "heat-shock" proteins people produce during fever to protect cells from damage.
Dr. Zimmerman and other researchers conducted a separate study to test a potential autism treatment, based in part on the heat-shock response theory. His team gave a supplement containing sulforaphane to 30 teenage and adult males with autism spectrum disorder.7 Sulforaphane, a chemical derived from broccoli sprouts, has "metabolic effects that in some ways resemble that of fevers."8 In this double-blind study, 15 males with autism were randomly assigned to take a placebo, or dummy pill; they served as a comparison group. More than half of those who took the real supplement saw behavioral improvements similar to those reported during fevers.8 As with fevers, the improvements faded when people stopped taking the supplement.
Those researchers noted that their theory and the supplement need more study, and with larger groups of people. Generally, scientists want to make sure that a result did not happen by chance, so they test a theory or treatment on large groups of people who represent the population affected by a condition.
Ms. Grzadzinski also would like to see more research into fevers and autism. Her study relied on parents' recollection of their children's behaviors during fevers. The next step would be measuring behaviors objectively during and after fevers among a large number of people with autism, she explained.
She noted that current fever research stemmed from reports from parents about this phenomenon. "It's important for families to know that they are the motivation for this research, both because they reported this phenomenon, and because we want to find new treatments to help," Ms. Grzadzinski said.
References:
- Sullivan, R. C. (1980). Why do autistic children...? Journal of Autism and Developmental Disorders, 10(2), 231-241.
- Grzadzinski, R., Lord, C., Sanders, S. J., Werling, D., & Bal, V. H. (2017). Children with autism spectrum disorder who improve with fever: Insights from the simons simplex collection. Autism Research : Official Journal of the International Society for Autism Research, doi:10.1002/aur.1856 [doi] Abstract.
- Curran, L. K., Newschaffer, C. J., Lee, L. C., Crawford, S. O., Johnston, M. V., & Zimmerman, A. W. (2007). Behaviors associated with fever in children with autism spectrum disorders. Pediatrics, 120(6), e1386-92. doi:120/6/e1386 [pii]
- Zimmerman, A. (Undated). Autism speaks' got questions blog: Parents see son's autism ease during fever; ‘Anyone studying this?'. Retrieved from https://www.autismspeaks.org/blog/2015/03/20/parents-see-son%E2%80%99s-autism-ease-during-fever-%E2%80%98anyone-studying
- Fischbach, G. (2010). SFARI director's column: Fever's promising puzzle. Retrieved from https://www.sfari.org/news/blog/2010/directors-column-fevers-promising-puzzle
- Good, P. (2017). Simplifying study of fever's dramatic relief of autistic behavior. Clinical Nutrition ESPEN, 17, 1-7. doi:S2405-4577(16)30266-2 [pii]
- Singh, K., Connors, S. L., Macklin, E. A., Smith, K. D., Fahey, J. W., Talalay, P., & Zimmerman, A. W. (2014). Sulforaphane treatment of autism spectrum disorder (ASD). Proceedings of the National Academy of Sciences of the United States of America, 111(43), 15550-15555. doi:10.1073/pnas.1416940111. Abstract.
- Singh, K., & Zimmerman, A. W. (2016). Sulforaphane treatment of young men with autism spectrum disorder. CNS & Neurological Disorders Drug Targets, 15(5), 597-601. Abstract