Animal study indicates that neonatal exposure to the anesthetic sevoflurane may lead to abnormal social behaviors.

A review of: Maiko Satomoto, Yasushi Satoh, Katsuo Terui, Hideki Miyao, Kunio Takishima, Masataka Ito, Junko Imaki (2009). Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice Anesthesiology, 110 (3), 628-637 DOI: 10.1097/ALN.0b013e3181974fa2

NOTE: THIS IS A PRE-CLINICAL (ANIMAL) STUDY.

I will keep my reviews of animal studies short and I want to emphasize that these type of studies are intended only to inform future research with animals and humans, and no extrapolations of these findings to humans should be made. This is of great importance because most findings obtained with animals are eventually not replicated with humans. That is, our field is littered with interesting, controversial, and often shocking animal findings that simply eventually didn’t apply to humans. In addition, animal models of specific conditions are by definition limited, in that animal dysregulation of behavior does not necessarily parallel human processes. For example, lack of social interactivity in the mice does not necessarily reflect “mice autism,” just like limited social interactivity in humans does not by itself reflect autism. Animal work is of utmost importance but we must use caution when reaching conclusions from such findings.

A number of studies have examined the effects of neonatal exposure to anesthesia on brain development, yet little is known about the possible effects of pediatric anesthesia on social functioning. In this study the authors examined the effects of sevoflurane on the social development of mice. The researchers reported that neonatal exposure to sevoflurane resulted in neurodegeneration in the caudate/putamen, retrosplenial cortex, dorsal hippocampal commisuure, and neocortex. Neonatal exposure also resulted in normative responses to novel environment (normal fear behaviors) but significantly less social behaviors. For example, when given the option, typical mice spend more time interacting with other mice than with objects. However, under the same environment, mice exposed to sevoflurane during the neonatal period spend more time interacting with objects than other mice. Furthermore, mice exposed to sevoflurane displayed impaired social memory when compared to non-exposed mice.

As previously stated, this study presents very preliminary animal evidence that a common pediatric anesthetic produces brain neurodegeneration and social impairment in mice. The authors correctly called for the need for additional animal and human research that could examine whether the risk of neonatal exposure to sevoflurane in regards to social functioning is also found in humans. Currently, there is no evidence that such association exists.

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3 Responses to Sevoflurane and Autism: Animal evidence of neonatal anesthesia risk?

  1. Lindsay says:

    This sounds somewhat similar to the research on endogenous opioids in the 1990s.

    Jaak Panksepp had proposed that maybe the social unresponsiveness in autism comes from an overactive endogenous-opioid system that prevents autistic people from experiencing loneliness as a bad thing. Because being alone did not distress them, they never learned to reach out to other people, I think the reasoning went.

    Later researchers running with this hypothesis did find autistic-like behaviors (asociality, stereotypy) in monkeys treated with opioids, which led to speculation that those monkeys might constitute an animal model of autism, and that the endogenous-opioid system might underlie autism in humans.

    Clinical trials of opioid blockers in autistic humans were uneven, with some showing a small effect and some showing no difference from placebo.

    I think that research, as well as the mouse research you have summarized, definitely shows that there is some connection between feelings of distress (fear or pain) and the development of social behavior in baby mammals. But, as you say, autism involves a lot more than just failure to develop normal social behavior.

  2. Another fascinating post Nestor.

    Your comments about the limits of animal studies are interesting. I assume that a major difficulty arises from the near impossibility of conducting actual experimental studies on children?

    What about survey type studies to see what percentage of people with autism received pediatric anesthesia compared to non autistic populations? Would that be a reasonable follow up on the animal studies?

    Note: My son with Autistic Disorder did in fact receive anesthesia for an operation during his first year.

  3. Thank you Harold and Lindsay for your comments.

    @harold, although such type of research would help clarify the question, you still have to deal with a major confound: all kids who are exposed to general anesthesia have some major issue that require surgery. So it would be nearly impossible to determine whether the effects observed (hypothetical increased rates of autism) are due to the anesthesia, to the actual surgery, or to other factors associated with the surgery, recovery, etc etc.

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