Autism Spectrum Disorders

  • Theoharis C. Theoharides
  • Irene Tsilioni


Autism spectrum disorders (ASD) are characterized by deficits in sociability and communication, as well as severe anxiety and stereotypic movements. Moreover, over 50 % of children with ASD experience atopic symptoms indicative of mast cell (MC) activation (asthma, eczema, food allergies and/or intolerance) which correlate with the presence of brain auto-antibodies. ASD pathogenesis is unknown preventing the development of effective treatments. As a result, more than 70 % of children with ASD are prescribed psychopharmacologic agents that often have little benefit and serious adverse effects. Increasing evidence indicates that local brain inflammation is involved in ASD. In particular, there is activation and proliferation of microglia, which communicate with MCs, located perivascularly primarily in the thalamus and hypothalamus, as well as the lining of the ventricles. MCs are stimulated by corticotropin-releasing hormone (CRH) and neurotensin (NT) secreted from the hypothalamus under stress; these peptides can also induce each other’s surface receptors leading to autocrine and paracrine effects. Stimulated MCs release inflammatory and neurotoxic mediators that disrupt the blood-brain barrier (BBB), activate microglia and cause focal inflammation. CRH and NT are significantly increased in serum of ASD children compared to normotypic controls. Addressing the “allergic” and anxiety symptoms would not only improve the health of the patients, but could also potentially reduce the core symptoms of ASD. Use of the natural anti-inflammatory flavonoid luteolin, in an olive fruit oil preparation to increase oral absorption, appears to provide significant benefit and should be investigated further. Treatment approaches targeting brain inflammation could have a great benefit.


Autism spectrum disorders (ASD) Corticotropin-releasing hormone (CRH) Mast cells (MCs) Microglia Neurotensin (NT) 



Aspects of the work discussed were funded in part by the Autism Research Institute, the National Autism Association, Safe Minds and The Jane Botsford Johnson Foundation.

Competing Interests 

The authors declare they have no competing interests.


TCT has been awarded US Patents No 8,268,365; 9,050,275 and 9,176,146 covering the treatment of brain inflammation and ASD.


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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and PathobiologyTufts University School of MedicineBostonUSA
  2. 2.Department of Internal MedicineTufts University School of Medicine and Tufts Medical CenterBostonUSA
  3. 3.Department of PsychiatryTufts University School of Medicine and Tufts Medical CenterBostonUSA

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