Autism

Addressing Sleep Problems May Be Key to Treatment of Aggressive Behavior in Patients with Autism

autism aggressive behavior treatment

If you are the parent of a child with autism spectrum disorder (ASD) who displays aggressive behaviors, you’re not alone: estimates indicate that about one in every four children who are diagnosed with autism fall within the clinical range on commonly-used aggressive behavior scales, and this symptom is the primary cause of residential placement for patients with autism. Unfortunately, among the widely varying physical and behavioral symptoms associated with autism, aggressive behavior can be one of the most challenging to treat. This is largely because the etiology of behavioral problems is so poorly understood: scientists hypothesize that aggressive behaviors in patients with ASD are caused by a complex combination of biological, behavioral, and environmental factors but have yet to develop a fully comprehensive model for understanding the underpinnings of this common symptom.

Currently, the standard recommendation for autism patients displaying aggressive behavior is antipsychotic medication. In 2006, risperidone (a second-generation antipsychotic) was approved for patients as young as five years old. Several controlled studies indicate it can be effective for treating aggressive behavior in autism patients during childhood, so it has become one of the most widely used medications in the field. The other FDA-approved option is aripiprazole, a similar antipsychotic drug. These medications have clear safety benefits over clozapine, which was the medication that was most commonly used in the past, but they lack consistent efficacy and can produce unwanted side effects like weight gain and daytime drowsiness. Therefore, scientists are still exploring pharmacological options that could be considered for FDA approval in the future, such as haloperidol, olanzapine, lurasidone, quetiapine, and sertraline. Preliminary small-scale, open-label studies suggest that these drugs may offer benefits for some patients.

Although lab-based and clinical research has historically focused on pharmacological therapeutics, many parents and practitioners are increasingly interested in alternative options. Not only are there concerns about the side effects and overall efficacy of pharmaceutical therapies for treating aggressive behavior in patients with autism, but some parents simply want to avoid starting their child on a prescription medication so early in life. Still, the lack of understanding of the basis of aggressive behavior makes it difficult to address directly, so some researchers are exploring an innovation solution: targeting conditions that are statistically associated with the symptom. Specifically, scientists have recently observed significant correlations between aggressive behaviors and sleep problems in children with autism. This has led to the hypothesis that it may be possible to effectively reduce aggressive behavior with butyric acid, which address sleep problems.

The Connection Between Autism and Sleep Problems

There are multiple studies suggesting a relevant clinical connection between aggressive behaviors in patients with autism and sleep problems. One particularly strong paper from 2015, which was published by a group of researchers from Oregon Health and Science University, assessed the prevalence and correlation between aggressive behaviors and a variety of other co-varying conditions in a large clinical sample of 400 patients between the ages of 2 and 16 years. Recognizing that the roots of aggressive behavior are poorly understood in patients with autism, their goal was to identify better-understood conditions that could be targeted more effectively in the hopes that the therapy would address both the aggressive behavior and the co-morbid condition. Chronic sleep problems was one of the conditions that immediately stood out as a feasible target.

Consistent with previous studies, the OHSU researchers found statistically significant associations between aggressive behavior and scores on a survey that measured eight different sleep domains among patients with autism, including:

  • Bedtime resistance
  • Latency in sleep onset
  • Sleep duration
  • Anxiety related to sleep
  • Late-night wakeups
  • Disordered breathing during sleep
  • Parasomnias
  • Daytime sleepiness

Based on this data, the authors concluded that sleep problems were a practicable target in future treatment strategies designed to reduce aggressive behavior problems in children with ASD.

The Relationship Between Short Chain Fatty Acids and the Circadian Clock

The next question, of course, is how best to address sleep problems in patients with autism. Traditional over-the-counter sleep aids like diphenhydramine HCl are always an option, but drowsiness and dizziness are common side effects—the same side effects, in fact, that many parents are trying to avoid by seeking alternatives to antipsychotics. Also, because sleep problems in patients with autism tend to be chronic, an over-the-counter sleep aid is not suitable, since these are intended for periodic (not regular) usage, and children can develop tolerance over time.

One promising option is to address abnormalities in the gut microbiome. According to one recent study, the presence of short chain fatty acids in the gut has an important role in the regulation of the circadian clock, which influences sleep and wake cycles. In a 2018 study in mouse models, a group of researchers from Waseda University in Tokyo, Japan, found that the concentrations of short chain fatty acids in the gut—including butyrate, acetate, and propionate—could directly modulate the functioning of the circadian clock. These short chain fatty acids are produced by bacteria in the gut when they ferment fibers that humans cannot digest. Therefore, the researchers suggested that increasing the dietary intake of prebiotic fiber, either through whole foods or through supplementation, could help improve outcomes for patients suffering from sleep problems.

Based on this finding, another option for patients with autism would be to introduce short chain fatty acids directly into the gut with a butyrate supplement. The scientists who produced this paper did not focus on autism patients, but some studies suggest that patients with autism may lack healthy concentrations butyrate-producing gut bacteria. For these patients, directly supplementing with butyrate might be more effective for reducing sleep problems than taking prebiotic fiber and assuming that the patient’s microbiome is healthy enough to ferment the fiber and produce the circadian-clock-regulating butyrate as expected. Supplementation is also ideal for patients with ASD since sensory inputs surrounding food can often trigger symptoms, including aggressive behavior.

Of course, parents and practitioners must recognize that the study was conducted in mice, so it is not entirely clear whether supplements like prebiotic fiber and butyrate will have similar effects on the circadian clock in humans. Nevertheless, for those who are looking to indirectly target aggressive behavior in autism patients through a closely correlated condition—that is, sleep problems—trying a butyrate supplement and/or choosing a diet that is high in prebiotic fiber is a relevant strategy to try. Another option to consider is melatonin, a hormone supplement that has been shown to help resolve sleep problems in children with autism in early studies. In the future, clinical studies can help resolve questions about how best to harness the correlation between sleep problems and aggressive behavior in patients with autism for the development of optimal treatments.

At Foundational Medicine Review, we analyze and synthesize the latest and most relevant research on a wide range of complex conditions, including autism. Join our mailing list to stay abreast of emerging scientific literature and news.

Works Cited

Cermak SA, Curtin C, Bandini LG. 2010. Food selectivity and sensory sensitivity in children with autism spectrum disorders. Journal of the American Dietetic Association. 110(2):238-246. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601920/

Chen C, Shen YD, Xun GL, Cai WX, Shi LJ et al.  2017. Aggressive behaviors and treatable risk factors of preschool children with autism spectrum disorder. Autism Research. 10(6):1155-62. https://www.ncbi.nlm.nih.gov/pubmed/28266803

DeFillipis M, Wagner KD. 2016. Treatment of autism spectrum disorder in children and adolescents. Psychopharmacology Bulletin. 46(2):18-41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044466/

Farmer C, Butter E, Mazurek MO, Cowan C, Lainhart J et al. 2015. Aggression in children with autism spectrum disorders an a clinic-referred comparison group. Autism. 19(3):281-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331245/

Felt BT, Chervin RD. 2014. Medications for sleep disturbances in children. Neurology Clinical Practice. 4(1):82-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943656/

Hill AP, Zuckerman KE, Hagen AD, Kriz DJ, Duvall SW et al. 2014. Aggressive behavior problems in children with autism spectrum disorders: Prevalence and correlates in a large clinical sample. Research in Autism Spectrum Disorders. 8(9):1121-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160737/

LeClerc S, Easley D. 2015. Pharmacological therapies for autism spectrum disorder: A review. 40(6):389-97. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450669/

Malow BA, Adkins KW, McGrew SG, Wang L, Goldman SE et al. 2012. Melatonin for sleep in children with autism: A controlled trial examining dose, tolerability, and outcomes. Journal of Autism and Developmental Disorders. 42(8):1729-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368078/

Pivovarciova A, Hnilcova S, Ostatnikova D, Mace FC. 2015. Bio-behavioral model of aggression in autism spectrum disorders: Pilot study. Bratislavske Lekarske Lisky. 116(12):702-6. https://www.ncbi.nlm.nih.gov/pubmed/26924148

Strati F, Cavalieri D, Albanese D, DeFelice C, Donati C et al. 3017. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 5:24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320696/

Tahara Y, Yamazaki M, Sukigara H, Mohotashi H, Sasaki H, Miyakawa H et al. 2018. Gut microbiota-derived short chain fatty acids induce circadian clock entrainment in mouse peripheral tissue. Scientific Reports. 8:1395. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780501/

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