MHL, 2000 McElderry St., Baltimore, MD 21205, USA.
Med Hypotheses. 2011 May;76(5):653-60. doi: 10.1016/j.mehy.2011.01.024. Epub 2011 Mar 8.
Human alpha-fetoprotein is a pregnancy-associated protein with an undetermined physiological role. As human alpha-fetoprotein binds retinoids and inhibits estrogen-dependent cancer cell proliferation, and because retinoic acid (a retinol metabolite) and estradiol (an estrogen) can both initiate cellular gene transcription, it is hypothesized here that alpha-fetoprotein functions during critical gestational periods to prevent retinoic acid and maternal estradiol from inappropriately stimulating gene expression in developing brain regions which are sensitive to these chemicals. Prenatal/maternal factors linked to increased autism risk include valproic acid, thalidomide, alcohol, rubella, cytomegalovirus, depression, schizophrenia, obsessive-compulsive disorder, autoimmune disease, stress, allergic reaction, and hypothyroidism. It will be shown how each of these risk factors may initiate expression of genes which are sensitive to retinoic acid and/or estradiol - whether by direct promotion or by reducing production of alpha-fetoprotein. It is thus hypothesized here that autism is not a genetic disorder, but is rather an epigenetic disruption in brain development caused by gestational exposure to chemicals and/or conditions which either inhibit alpha-fetoprotein production or directly promote retinoic acid-sensitive or estradiol-sensitive gene expression. This causation model leads to potential chemical explanations for autistic brain morphology, the distinct symptomatology of Asperger's syndrome, and the differences between high-functioning and low-functioning autism with regard to mental retardation, physical malformation, and sex ratio. It will be discussed how folic acid may cause autism under the retinoic acid/estradiol model, and the history of prenatal folic acid supplementation will be shown to coincide with the history of what is popularly known as the autism epidemic. It is thus hypothesized here that prenatal folic acid supplementation has contributed to the post-1980 increase in US autism diagnoses. In addition to explaining the epidemic within the wider retinoic acid/estradiol model of causation, this theory leads to potential explanations for certain genetic findings in autism, autistic regression, and changing trends in autism symptomatology with regard to mental retardation, wheat allergy, and gastrointestinal problems.
人甲种胎儿蛋白是一种与未确定的生理作用有关的妊娠相关蛋白。由于人甲种胎儿蛋白结合视黄酸并抑制雌激素依赖性癌细胞增殖，并且由于视黄酸（视黄醇的代谢产物）和雌二醇（一种雌激素）都能起始细胞基因转录，所以在这里假设甲种胎儿蛋白在关键妊娠期中起作用，以防止视黄酸和母体雌二醇不恰当地刺激对这些化学物质敏感的发育中脑区的基因表达。与自闭症风险增加相关的产前/母体因素包括丙戊酸、沙利度胺、酒精、风疹、巨细胞病毒、抑郁、精神分裂症、强迫症、自身免疫性疾病、应激、过敏反应和甲状腺功能减退。将表明这些风险因素中的每一个如何通过直接促进或通过减少甲种胎儿蛋白的产生来起始对视黄酸和/或雌二醇敏感的基因的表达。因此在这里假设自闭症不是遗传疾病，而是由于妊娠期间接触化学物质和/或条件而导致的脑发育中的表观遗传破坏，这些化学物质和/或条件抑制甲种胎儿蛋白的产生或直接促进视黄酸敏感或雌二醇敏感的基因表达。该因果模型为自闭症患者的大脑形态、艾斯伯格综合征的独特症状学以及高功能和低功能自闭症在智力迟钝、身体畸形和性别比例方面的差异提供了潜在的化学解释。将讨论视黄酸/雌二醇模型下叶酸如何导致自闭症，并且将表明产前叶酸补充的历史与普遍称为自闭症流行的历史相吻合。因此在这里假设产前叶酸补充剂促成了 1980 年后美国自闭症诊断的增加。除了在更广泛的视黄酸/雌二醇因果模型内解释流行外，该理论为自闭症中的某些遗传发现、自闭症的退行以及智力迟钝、小麦过敏和胃肠道问题方面的自闭症症状学变化趋势提供了潜在的解释。
