Are mast cells involved in autism?
Increasing evidence albeit indirect and circumstantial suggest that neurochemicals released by mast cells as a result of a variety of triggers like infection, intestinal bacteria, food allergies and toxins may be responsible for autism spectrum disorders in at least a subset of the patients.
The involvement of mast cells is supported by the fact that there are alterations in 5HT or serotonin in patients with ASD. High 5HT or serotonin levels have bidirectional impact on not just the brain but also the gut.
What do mast cells do?
Mast cells are postulated to play a key role in immune system, allergies including eczema, autoimmune disorders like multiple sclerosis, rheumatoid arthritis etc. Clinical manifestations are varied including headache/migraine, abdominal migraine , skin allergies and eczema, respiratory allergies, and food allergies, asthma, urticaria, gastrointestinal disturbances, many of which appear to be more common in autism.
One way to prove if the hypothesis is correct is by using agents that inhibit mast cell activation and/or some of the neurochemicals released by mast cells.
Autism-mast cell hypothesis:
Increased serotonin levels or hyperserotonaemia may be a pathologic factor in autism and cyproheptadine, a histamine-1 as well as 5-HT2 antagonist as well as a inhibitor of mast cell activation is of benefit for treatment.
What is cyproheptadine used for?
According to the NIH/NCBI publications in the US National Library of Medicine, "Cyproheptadine relieves red, irritated, itchy, watery eyes; sneezing; and runny nose caused by allergies, irritants in the air, and hay fever. It may also be used to relieve the itching of allergic skin conditions, and to treat hives, including hives caused by exposure to cold temperatures and by rubbing the skin."
Dr. Akhondzadeh and colleagues from the Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, conducted the study and published their results in the Journal of Clinical Pharmacy and Therapeutics.
- Randomized, double-blind, placebo-controlled trial
- 40 kids between 3 and 11 years and with diagnosis of autism
- Outpatients specialty clinic at University Psychiatric Teaching Hospital
- Chief clinical manifestation: severely disruptive symptoms
- Comparison of cyproheptadine + haloperidol versus haloperidol alone (+ placebo)
- Patients assessed at baseline and after 2, 4, 6 and 8 weeks
- Dose: haloperidol titrated to maximum 0.05 mg/kg/d and cyproheptadine titrated up to maximum 0.2 mg/kg/day
Autism-cyproheptadine study outcome measures
- Aberrant Behaviour Checklist-Community (ABC-C)
- Childhood Autism Rating Scale (relating to people and verbal communication
- Side effects and extrapyramidal symptoms recorded using a checklist and the Extrapyramidal Symptoms Rating Scale
Autism-cyproheptadine study results showed improvement in cyproheptadine group
- ABC-C scores improved with cyproheptadine plus haloperidol as compared to haloperidol alone. Patients in cyproheptadine demonstrated a significant mean decrease in ABC score of −10.9 compared to a mean decrease of −3.7 in patients receiving placebo
- Childhood Autism Rating Scale scores improved with cyproheptadine + haloperidol as compared to haloperidol alone
- No significant difference in extrapyramidal symptoms side-effects
Autism-cyproheptadine study conclusions
Cyproheptadine combines with a conventional antipsychotic may be superior to conventional antipsychotic alone for patients with autistic spectrum disorder. Results of the study lend support to the hypothesis that mast cells may be involved in the pathogenesis of autism spectrum disorders.
Elbe and Lalani recently concluded in the Journal of Canadian Acad Child Adolescent Psychiatry that it may be considered for use on an off-label basis when FDA approved medications are not effective or cause significant undesirable effects.
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