Theoharis C Theoharides1, Duraisamy Kempuraj, Lyn Redwood. 1. Molecular Immunopharmacology and Drug Discovery Laboratory, Tufts University School of Medicine, Tufts Medical Center, Department of Pharmacology, Boston, MA 02111, USA. theoharis.theoharides@tufts.edu
Abstract
BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by difficulties in communication and by repetitive and stereotypic behaviors, as well as by social impairment, attention, cognitive, and learning defects. ASDs present in early childhood and their prevalence has increased significantly to 1/150 children. Despite a number of theories, the actual reasons for this increase are still not clear. There is no reliable screening test, and no definite pathogenesis or curative therapy. Consequently, there is a major gap hampering development of effective treatments. OBJECTIVE: To review recent publications on ASDs pathogenesis and treatment with emphasis on neuroimmune processes and new therapeutic approaches. METHODS: Mostly original papers (450) on epidemiology, possible pathogenesis or treatment of ASDs in Medline from 1990 to May 2009 were reviewed. All authors contributed to this review. RESULTS/ CONCLUSION: Increased oxidative stress and immune dysregulation are present in ASDs. Mast-cell activation may contribute to gut-blood-brain barrier disruption and brain inflammation. No effective treatments have emerged. Well-designed clinical trials with nonpsychotropic drugs were few and ASD characteristics varied considerably, making conclusions difficult. Psychotropic drugs are often used for stereotypic and aggressive behaviors. Unique combinations with antioxidant and anti-inflammatory flavonoids hold promise. New potential translational research areas and possible treatments are suggested.
BACKGROUND:Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by difficulties in communication and by repetitive and stereotypic behaviors, as well as by social impairment, attention, cognitive, and learning defects. ASDs present in early childhood and their prevalence has increased significantly to 1/150 children. Despite a number of theories, the actual reasons for this increase are still not clear. There is no reliable screening test, and no definite pathogenesis or curative therapy. Consequently, there is a major gap hampering development of effective treatments. OBJECTIVE: To review recent publications on ASDs pathogenesis and treatment with emphasis on neuroimmune processes and new therapeutic approaches. METHODS: Mostly original papers (450) on epidemiology, possible pathogenesis or treatment of ASDs in Medline from 1990 to May 2009 were reviewed. All authors contributed to this review. RESULTS/ CONCLUSION: Increased oxidative stress and immune dysregulation are present in ASDs. Mast-cell activation may contribute to gut-blood-brain barrier disruption and brain inflammation. No effective treatments have emerged. Well-designed clinical trials with nonpsychotropic drugs were few and ASD characteristics varied considerably, making conclusions difficult. Psychotropic drugs are often used for stereotypic and aggressive behaviors. Unique combinations with antioxidant and anti-inflammatory flavonoids hold promise. New potential translational research areas and possible treatments are suggested.
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