About 17 years ago, when I acquired a personal interest in autism, the link to abdominal symptoms was mentioned in the literature but readily dismissed as coincidental. Throughout the years there has been increasing interest on the subject fueled, curiously enough, by highly speculative hypotheses often backed by little supportive evidence, e.g., leaky gut syndrome, autistic enterocolitis. The reason for this blog is that, if such a relationship proved to be non-coincidental, I would have sought for a simpler explanation. In essence the burden of proof should make use of the most parsimonious medically acceptable proposition, doing otherwise would lead to a type of infinite regress. In the case of autism and abdominal pains I would have first started by eliminating a possible link to migraines.
Both autism and migraines are conditions that are entirely diagnosed based on clinical history. In some children with family history of migraine,s abdominal pains, bloating, vomiting and diarrhea may occur as paroxysmal attacks usually starting around the mean age of 7 years. These paroxysms reach a peak by the age of ten and then gradually diminish and are replaced by the traditional headaches around the time of puberty; otherwise, headaches per se do not necessarily accompany the symptoms. These attacks are precipitated by sounds, lights and/or smells in patients that may show a variety of autonomic symptoms such as pallor and flushing of the skin. Foods are usual triggers for abdominal migraines. Common culprits include cow’s milk, chocolate, cheese, wheat products, rye, and baked beans. Intolerance to a large range of foods have led some investigators to suggest that abdominal migraines are a type of food allergy that can be treated by diets. Many of these factors offer a commonality to autism. However, the most striking commonality is that a significant percentage (about 30%) of both migraneurs and autistic individuals have elevated levels of a chemical in the blood called serotonin.
The large majority of serotonin is found in cells lining the gut. The action of serotonin in the gut may help explain many of the previously related symptoms (see figure below) but at the same time may offer hope for a therapeutic intervention. Current management of migraine includes serotonergic agents (called “agonists” because they propitiate actions of the same) during acute episodes and anticonvulsants as migraine prophylactics. Migraneurs, like autistics, also exhibit a hyperexcitable cerebral cortex with epileptiform activity reported during the active headache phase. It has been reported that the visual auras and discomfort, as well as illusions, of migraneurs are manifestations of their hyperexcitable cortex.
In patients where their serotonin level have been increased as a side effect of medications (e.g., antidepressants) there may be a rapid onset of symptoms characterized by agitation, diarrhea, hallucinations, nausea, vomiting, changes in body temperature, and movements that become less coordinated than usual.
The figure illustrates the rich role serotonin plays in gut function. The chemical name of serotonin is 5-hydroxytriptamine which is abbreviated as 5-HT.
Abdominal migraine is episodic with recovery between attacks. The differential diagnosis includes episodic abdominal conditions such as biliary disease, partial bowel obstruction and irritable bowel syndrome. Oliver Sacks has stated that with migraine equivalents: “…indeed there is probably no field in medicine so strewn with the debris of misdiagnosis and treatment, and of well-intentioned but wholly mistaken medical and surgical interventions”. Least to say the misdiagnosis of migraine equivalents is a common occurrence leading to multiple referrals among a variety of medical specialties and invasive studies such as endoscopy.
Are migraines more common in autistic individuals? Nobody knows for sure. Large scale studies have not been performed. There are many apocryphal patient reports within the internet. In a recent pole in the Wrong Planet among self-reported adult ASD patients (146 responses) females with migraines far outweighed those without 42 to 9%. Among males, the ratio was smaller, migraneurs still outnumbering those without headaches: 36 to 11%.
Several years ago I wrote an article about the commonalities of migraines and abdominal symptoms in autistic patients (Casanova, 2008) . The article emphasized the following: Both autism and migraine are defined by serotonergic abnormalities and a hyperexcitable cortex. Other commonalities exist in regards to clinical history and laboratory findings making the hypothesis empirically meaningful. Difficulties in establishing a relationship stem from the fact that diagnostic criteria for migraine rely exclusively on a good history. Autistic patients have deficits in language development which makes it difficult for them to communicate symptoms. However, electrophysiological methods may bypass collection of history and provide for outcome measures making the hypothesis falsifiable. In this regards methods such as transcranial magnetic stimulation (TMS) may simultaneously provide for outcome measures of cortical hyperexcitability and provide for potential interventions. See my previous blog on TMS https://corticalchauvinism.wordpress.com/2013/01/27/why-use-transcranial-magnetic-stimulation-tms-in-autism/
The discovery of hyperserotonemia in 1961 by Schain and Freedman gave rise to a putative intervention with a drug that causes the long term depletion of serotonin: fenfluramine. After some promising results, the drug showed great variability of effects and no improvements in large clinical trials. Ultimately the drug was withdrawn from the US market after reports of some serious side effects that included heart valve disease, pulmonary hypertension and cardiac fibrosis. It is thus important to cautiously consider any conclusions before translating findings into clinical trials, e.g. serotonergic drugs and nitric oxide synthase inhibitors. Such attempts provide an opportunity for symptomatic treatment but otherwise remain far removed from providing a cure.
Casanova MF. The minicolumnopathy of autism: a link between migraines and gastrointestinal symptoms. Med Hypothesis 70(1):73-80, 2008.
Sacks O. Migraine. Vintage Press, 1999.
[Addendum 5/12/13: People interested in this line of thinking can also read about a condition called “cyclical vomiting syndrome”. Although the cause is unknown, some people relate the same to migraines. It has been treated with some success with the antihistamine cyproheptadine (Periactin) and/or the antidepressant amytriptiline. The mechanisms of action of these drugs in migraine is not known. Other people have recommended a gluten casein free diet. Some migraine attacks can be precipitated precipitated by eating chocolate, caffeine, alcohol, cheese, etc. Try to rule out food triggers for your migraines. Remember that recurrent vomiting can dehydrate a person. For some additional information see: http://pediatrics.about.com/cs/weeklyquestion/a/cyclic_vomiting.htm ]