Chapter

Neuroimmune Pharmacology

pp 643-659

Date:

Autism Spectrum Disorders

  • Theoharis C. TheoharidesAffiliated withMolecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of MedicineDepartment of Internal Medicine, Tufts University School of Medicine and Tufts Medical CenterDepartment of Psychiatry, Tufts University School of Medicine and Tufts Medical Center Email author 
  • , Irene TsilioniAffiliated withMolecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine

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Abstract

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.

Keywords

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