Autism Action Month: 12-month autism research recap 2018
Autism Awareness is not enough – April is Autism Action Month:
2017-2018 research & science year in review
1. GUT PROBLEMS IN AUTISM – AGAIN AND AGAIN AND AGAIN
The old parental observation that what goes on in the gut is very much linked to what goes on in the children’s brains has been confirmed. Several times over!
A review of more than 150 papers found a large body of evidence showing that restoring a healthy balance of gut bacteria can reduce autism symptoms. The study observed that the first scientific reports on the links between gut bacteria and autism symptoms and behaviours go all the way back to the 1960s.
We also learned that the bacteria in the mouths of children with autism are very different to those of neurotypical children. The difference was so striking that the authors suggested their test could in future be used to help diagnose autism!
One of the bacterial species found in large amounts in the mouths of children with autism was Streptococcus, “a potent immunogenic trigger”, which produces neurotoxins that can cause central nervous system dysfunctions such as tics, obsessive-compulsive behaviours (think PANS and PANDAS), and movement and coordination disorders (think every other child with autism). Rothia species of bacteria were also highly abundant in kids with autism. Because its levels were correlated to severity of autism, the authors suggested that it “might be involved in systemic inflammation and immune response in the pathogenesis of ASD”.
Going further down the GI tract, we found that Small Intestinal Bacterial Overgrowth (SIBO) is present in many children with autism and that it is significantly associated with more severe symptoms of autism. However beneficial huge numbers of bacteria may be in the lower intestine, the small intestine generally accommodates small amounts comparatively, so SIBO is bad news indeed.
Various other teams of scientists also found altered microbiota in other parts of the gut in autism, as well as evidence of immune alterations–such as raised levels of immunoglobulin A–and mitochondrial dysfunction. For those who have been following the developments in the increasingly fascinating field of mitochondria (the energy-producing organelles in the cells) and metabolic dysfunction in autism, we now know that the functioning of mitochondria in the guts of children with autism is significantly different from other groups of children with similar gut symptoms.
We found out that the prevalence of Coeliac Disease (CD) in autism is very high, even in those children without any gastrointestinal complaints. So if a child doesn’t ‘look’ like they react to gluten, their body still might be having a problem with it. Coincidentally, another team of scientists revealed at about the same time that children with CD are at increased risk for most psychiatric disorders, including autism, while a third group of researchers found a sound biological explanation for wheat sensitivity: systemic immune activation due to breakdown of intestinal barrier.
A very large study in the US looked at thousands of medical records and found high rates of Inflammatory Bowel Disease in autism. The authors concluded that those and other gut problems in autism are likely linked to systemic inflammation.
“Our review looked at taking probiotics, prebiotics, changing the diet — for example, to gluten — and casein-free diets, and faecal matter transplants. All had a positive impact on symptoms… such things as increased sociability, a reduction in repetitive behaviour, and improved social communication — all hugely beneficial to the life of an ASD sufferer.”
2. HEALTH IN AUTISM – Do people suffer ill health because of autism, or do they have autism because they are/were unwell?
We have had further confirmations of the link between medical problems and autism. Children and adults with autism suffer from many more medical problems than the general population, and on average die much younger–the average life expectancy is only 39 years for those with severe autism, and around 58 for those on the mildest end of the spectrum. This bad health seems to be linked to whatever is causing autism too–babies and toddlers who suffer bad health early on, those who are born very prematurely, or those born to mothers who have suffered ill health during pregnancy, have much higher chances of developing symptoms of autism.
The biggest medical problem in autism, and the biggest killer, is seizure disorders, followed by various metabolic, mitochondrial, neurological, immune, gastrointestinal, psychiatric, cardiovascular and respiratory diseases and disorders. The severity of these conditions most often correlates with the severity of autism.
In addition, many medical conditions are often hard to identify and diagnose in autism. This is often due to diagnostic overshadowing, where initial signs are symptoms manifest as behaviours and, sadly, are dismissed as ‘just autism’.
On the positive side, successful identification and treatment of those conditions–many of which seem not to be occurring merely ‘in parallel’ with autism but are actively causing or worsening the very symptoms of autism– often leads to improvements not only in health but also in the severity of those autism symptoms and behaviours.
In conclusion, the findings of the past twelve months add further weight to the large body of evidence showing that challenging behaviours in autism, such as aggression, self-harm, irritability, tantrums, sleep disturbances, strange feeding and dietary problems, obsessive, repetitive, anxious-avoidant and others often have a physical cause. The first line approach for tackling challenging behaviours in autism should be investigation and treatment of possible underlying medical causes.
“Malow et al., (2006) reported a notable example that autistic manifestation was decreased after adenotonsillectomy (AT) for treatment of obstructive sleep apnea (OSA) in a 5-year-old female with ASD.
In the present study, we also found a significant improvement of the features of ASD such as withdrawal behavior (derives little enjoyment from social activity, prefers to be alone, will not talk, secretive, shy, etc.), social problems (behaving immaturely, does not get along with others, is teased, not well-liked, etc.), and thought problems (absent-minded, self-injury, engages in repetitive and/or strange behaviors, etc.) besides ADHD-like symptoms after OSA treatment in 30 ASD children with OSA” (Murata 2017)
3. TREATMENT TRIALS: the age of precision medicine. Or to state the obvious, treat the child, not the label!
After a longish period of slumber, this past year has given birth to several very promising novel (and not so novel) treatments for autism.
Treating ‘hidden’ seizures in autism brings about COGNITIVE and behavioural improvements
A large majority of children and adults with autism suffer from subclinical (invisible) seizure activity in their brains, even when they don’t suffer full blown (visible) epilepsy. It has long been wrongly assumed that normalising abnormal brain activity does nothing to improve brain function and therefore many parents seeking treatment for their children have been dismissed. However, current research shows that normalising abnormal brain activity (‘decreasing subclinical epileptiform discharges’ in science speak) does actually improve brain function and behaviours. Oh, and yes, it does reduce autism symptoms too.
Century-old drug offers new hope for autism treatment
It was fascinating to read the findings of the suramin study, seeing how a 100-year old drug successfully reduced symptoms of autism. The study was well designed and meticulously carried out. STOP PRESS! We have just learned that the authors have now secured the large funding needed for the next phase of this research.
New autism treatment could come from altering gut microbiota
In addition to the aforementioned large scientific review that concluded, on the basis of all available evidence, that targeting gut microbiome through diets and supplements can have a positive impact on autism symptoms, another brand new trial showed that children with autism may benefit from microbiota transfer therapy (MTT). This is the first time that scientists have shown positive long-term effects of MTT on improving both gastrointestinal and behavioural symptoms in children with autism.
Diuretic drug improves core autism symptoms
Following on from the promising results of their earlier preliminary trials, a team of French researchers and clinicians have recently tested bumetanide again on a larger group of children, and found it decreased the severity of core autism symptoms, and did so in a dose-dependent manner.
A single therapy benefits both stuttering and autism
Adrenocorticotropic hormone therapy in patients with night-time subclinical seizure activity improves their stuttering and autism symptoms alongside EEG readings. Read more.
Treating sleep apnoea can improve symptoms of autism
Researchers in Japan showed that correcting obstructive sleep apnoea in children with autism spectrum disorders can significantly improve their behaviour. Read more.
Some other treatment trials of interest:
Inflammation, seizures and brain function, once again
Finally, in a stunning and unexpected discovery a team of researchers has just discovered evidence of massive immune activation in the brains of children with epilepsy. While this study did not include any children with autism the finding is very pertinent, as up to one third of ASD children develop epilepsy at some point in their lives, and a large majority–over 80% by some counts–suffer chronic subclinical seizure activity in the absence of full blown, visible epilepsy.
Interestingly enough, another study was published recently in which scientists observed lifelong abnormal EEG brain seizure activity in a rodent model of autism. Newborn animals exposed to immune activation shortly after birth–a standard way of creating animals with neurodevelopmental and behavioural abnormalities–developed both social/behavioural oddities as well as EEG readings that were identical to those found in humans with autism.
Both teams are hopeful that their findings will lead to better and more targeted treatments for both epilepsy and autism, including anti-inflammatory immunological treatments.
More than ever, scientific discoveries are confirming what parents of children with autism have been observing and reporting for years. The field of autism research is–thankfully!– ever-evolving and very lively at present, with forward-thinking researchers and practitioners seeking answers rather than relying on unproven assumptions, developing new treatments and repurposing old ones for the comorbidities and disability associated with autism. Parents matter, and their actions and words count, and we encourage you to keep pressing and ACTING for a better present and future for our children. We hope that you can share this work and any other documents we’ve prepared to enlighten and educate people around you.
“Increasing evidence suggests a role for inflammation in neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous work in rodents has established that immune activation during critical developmental periods can cause phenotypes that reproduce core features of ASD, including decreased social interaction, aberrant communication, and increased repetitive behavior. In humans, ASD is frequently associated with comorbid medical conditions including sleep disorders, motor hyperactivity, and seizures.
Here we use a ‘two-hit’ immune-activation paradigm to determine whether perinatal immune activation can also produce these comorbid features in mice. In this paradigm, we treated timed-pregnant mice with…Poly I:C, which simulates a viral infection…A subset of the offspring also received a second ‘hit’ of lipopolysaccharide (LPS), which simulates a bacterial infection, on postnatal day 9.
At 6 weeks of age, mice were implanted with wireless telemetry transmitters…Both prenatal Poly I:C and postnatal LPS produced changes in locomotor activity and temperature patterns, increases in slow-wave sleep, and shifts in EEG spectral power…Postnatal LPS also produced persistent increases in spontaneous bursts of epileptiform activity (spike-wave discharges) that occurred predominantly during sleep.
Our findings demonstrate that early-life immune activation can lead to long-lasting physiologic perturbations that resemble medical comorbidities often seen in ASD and other neuropsychiatric conditions.” (Missig al. 2017)
Section 1: Gut health and gastrointestinal problems in autism
Butwicka A, et al. (2017) Celiac Disease Is Associated with Childhood Psychiatric Disorders: A Population-Based Study. J Pediatr. May;184:87-93.e1.
Kang DW, et al. (2017) Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. Anaerobe. Dec 22;49:121-131
Lee M, et al. (2017) Association of Autism Spectrum Disorders and Inflammatory Bowel Disease. J Autism Dev Disord. Nov 23.
Lee Y, et al. (2017) Rapid Assessment of Microbiota Changes in Individuals with Autism Spectrum Disorder Using Bacteria-derived Membrane Vesicles in Urine. Exp Neurobiol. Oct;26(5):307-317.
Li Q, et al. (2017) The Gut Microbiota and Autism Spectrum Disorders. Front Cell Neurosci. Apr 28;11:120. Article
Qiao Y, et al. (2018) Alterations of oral microbiota distinguish children with autism spectrum disorders from healthy controls. Sci Rep. Jan 25;8(1):1597. Article.
Rose S, et al. (2017) Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study. PLoS One. Oct 13;12(10):e0186377.
Strati F, et al. (2017) New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. Feb 22;5(1):24.
Wang L, et al. (2017) Hydrogen breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in autism. Eur Child Adolesc Psychiatry. Aug 10.
Zhou J, et al. (2017) Increased stool immunoglobulin A level in children with autism spectrum disorders. Res Dev Disabil. Nov 6.
Section 2: Health and medical conditions in autism
Ahmad SF, et al. (2017) Imbalance between the anti-and pro-inflammatory milieu in blood leukocytes of autistic children. Mol Immunol. Feb;82:57-65.
Bean Jaworski JL, et al. (2017) Rates of autism and potential risk factors in children with congenital heart defects. Congenit Heart Dis. Mar 16.
Careaga M et al. (2017) Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates. Biol Psychiatry. Mar 1;81(5):391-401.
Careaga M, et al. (2017) Immune Endophenotypes in Children With Autism Spectrum Disorder. Biol Psychiatry. Mar 1;81(5):434-441.
Colombo P, et al. (2017) Assessing mental health in boys with Duchenne muscular dystrophy: Emotional, behavioural and neurodevelopmental profile in an Italian clinical sample. Eur J Paediatr Neurol. Mar 24.
Dachew B, et al. (2018). Pre-eclampsia and the risk of autism-spectrum disorder in offspring: Meta-analysis. The British Journal of Psychiatry, 1-6.
Gentile I, et al. (2017) Prevalence of congenital cytomegalovirus infection assessed through viral genome detection in dried blood spots in children with autism spectrum disorders. In Vivo, Vol. 31, No. 3, May-June, 467-473.
Getahun D, et al. (2017) Association of Perinatal Risk Factors with Autism Spectrum Disorder. Am J Perinatol. Feb;34(3):295-304.
Gillberg C, et al. (2017) Febrile Seizures and Epilepsy: Association With Autism and Other Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden. Pediatr Neurol. Sep;74:80-86.e2.
Hornig M, et al. (2018) Prenatal fever and autism risk. Mol Psychiatry. Mar;23(3):759-766.
Krakowiak P, et al. (2017) Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder. Biol Psychiatry. Mar 1;81(5):442-451.
Lee AS, et al. (2017) Developmental microglial priming in postmortem autism spectrum disorder temporal cortex. Brain Behav Immun. May;62:193-202.
Logan JW, et al. (2017) Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm. J Perinatol. Jan 12.
Maher GM, et al. (2017) Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol. BMJ Open. Oct 5;7(10):e018313.
Miller KM, et al. (2017) Meconium exposure and autism risk. J Perinatol. Feb;37(2):203-207.
Mitchell R, et al. (2017) Risk factors for the development of autism spectrum disorder in children with tuberous sclerosis complex: protocol for a systematic review. Syst Rev. Mar 8;6(1):49.
Modabbernia A, et al. (2017) Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. Mar 17;8:13.
Muskens JB, et al. (2017) Medical comorbidities in children and adolescents with autism spectrum disorders and attention deficit hyperactivity disorders: a systematic review. European Child & Adolescent Psychiatry. July 3.
Patel S et al. (2017) Social impairments in autism spectrum disorder are related to maternal immune history profile. Mol Psychiatry. Oct 10.
Rom AL et al. (2018) Parental Rheumatoid Arthritis and Autism Spectrum Disorders in Offspring: A Danish Nationwide Cohort Study. J Am Acad Child Adolesc Psychiatry. Jan;57(1):28-32.e1.
Scott O, et al. (2017) Clinical clues for autoimmunity and neuroinflammation in patients with autistic regression. Dev Med Child Neurol. Apr 6.
Soke GN, et al. (2018) Prevalence of Co-occurring Medical and Behavioral Conditions/Symptoms Among 4- and 8-Year-Old Children with Autism Spectrum Disorder in Selected Areas of the United States in 2010. J Autism Dev Disord.
Tsao PC, et al. (2017) Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study. Eur Child Adolesc Psychiatry. Apr 17.
Yeong SY, et al. (2017) Reversing behavioural abnormalities in mice exposed to maternal inflammation. Nature, volume 549, pages 482–487.
Section 3: Treatment trials in autism
El-Rashidy O, et al. (2017) Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metab Brain Dis. Aug 14.
Kang DW, et al. (2017) Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017 Jan 23;5(1):10
Lee RWY, et al. (2018) A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder. Physiol Behav. Feb 5;188:205-211.
Missig G, et al. (2018) Perinatal Immune Activation Produces Persistent Sleep Alterations and Epileptiform Activity in Male Mice. Neuropsychopharmacology. Feb;43(3):482-491. link
Murata E, et al. (2017) Evaluation of behavioral change after adenotonsillectomy for obstructive sleep apnea in children with autism spectrum disorder. Research in Developmental Disabilities, May 14, Vol. 65, 127-39. link
Naviaux RK, et al. (2017) Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Ann Clin Transl Neurol.
Shaaban SY, et al. (2017) The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutr Neurosci. Jul 7:1-6.
Wang M, et al. (2017) Levetiracetam is associated with decrease in subclinical epileptiform discharges and improved cognitive functions in pediatric patients with autism spectrum disorder. Neuropsychiatr Dis Treat. Aug 31;13:2321-2326
Willfors C, et al. (2017) Medical history of discordant twins and environmental etiologies of autism. Transl Psychiatry. Jan 31;7(1):e1014.
Xu D, et al. (2018) Peripherally derived T regulatory and γδ T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy. J Exp Med. Feb 27.
Yang Y, et al. (2018) Targeting gut microbiome: A novel and potential therapy for autism. Life Sci. Feb 1;194:111-119. Epub Dec 23. Review.
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