Theoharides Theoharis C, Kempuraj Duraisamy, Redwood Lyn
Molecular Immunopharmacology and Drug Discovery Laboratory, Tufts University School of Medicine, Tufts Medical Center, Department of Pharmacology, Boston, MA 02111, USA.
Expert Opin Pharmacother. 2009 Sep;10(13):2127-43. doi: 10.1517/14656560903107789.
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.
To review recent publications on ASDs pathogenesis and treatment with emphasis on neuroimmune processes and new therapeutic approaches.
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.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征为沟通困难、重复刻板行为、社交障碍、注意力不集中、认知及学习缺陷。ASD在幼儿期出现，其患病率已显著上升至每150名儿童中有1例。尽管有多种理论，但患病率上升的实际原因仍不清楚。目前尚无可靠的筛查测试，也没有明确的发病机制或治疗方法。因此，这一重大差距阻碍了有效治疗方法的开发。
综述近期关于ASD发病机制及治疗的文献，重点关注神经免疫过程和新的治疗方法。
对1990年至2009年5月期间Medline数据库中有关ASD流行病学、可能的发病机制或治疗的450篇主要原创论文进行了综述。所有作者均参与了本综述。
结果/结论：ASD存在氧化应激增加和免疫失调。肥大细胞活化可能导致肠-血-脑屏障破坏和脑部炎症。目前尚未出现有效的治疗方法。针对非精神药物的精心设计的临床试验很少，且ASD的特征差异很大，难以得出结论。精神药物常用于治疗刻板行为和攻击性行为。与抗氧化和抗炎类黄酮的独特组合具有前景。文中提出了新的潜在转化研究领域和可能的治疗方法。
