Adams D D, Knight J G, Ebringer A
Faculty of Medicine, University of Otago, Box 913, Dunedin 9050, New Zealand.
ISRN Psychiatry. 2012 Apr 30;2012:758072. doi: 10.5402/2012/758072. Print 2012.
Schizophrenia is of mysterious causation. It is not infectious, not congenital, but shows familial aggregation, the Mendelian genetics indicating involvement of multiple codominant genes with incomplete penetrance. This is the pattern for autoimmune diseases, such as Graves' disease of the thyroid, where forbidden clones of B lymphocytes develop, and cause thyrotoxicosis by secreting autoantibodies that react with the thyroid gland's receptor for thyroid-stimulating hormone from the pituitary gland. In 1982, Knight postulated that autoantibodies affecting the function of neurons in the limbic region of the brain are a possible cause of schizophrenia. Today, this is even more probable, with genes predisposing to schizophrenia having being found to be immune response genes, one in the MHC and two for antibody light chain V genes. Immune response genes govern the immune repertoire, dictating the genetic risk of autoimmune diseases. The simplest test for an autoimmune basis of schizophrenia would be trial of immunosuppression with prednisone in acute cases. The urgent research need is to find the microbial trigger, as done by Ebringer for rheumatoid arthritis and for ankylosing spondylitis. This could lead to prophylaxis of schizophrenia by vaccination against the triggering microbe.
精神分裂症的病因成谜。它不具传染性，也非先天性疾病，但具有家族聚集性，孟德尔遗传学表明其涉及多个共显性基因且外显率不完全。这是自身免疫性疾病的模式，比如甲状腺的格雷夫斯病，在该病中，B淋巴细胞的禁忌克隆会发展，并通过分泌与垂体分泌的促甲状腺激素的甲状腺受体发生反应的自身抗体而导致甲状腺毒症。1982年，奈特推测影响大脑边缘区域神经元功能的自身抗体可能是精神分裂症的一个病因。如今，这种可能性更大了，因为已发现与精神分裂症易感性相关的基因是免疫反应基因，一个在主要组织相容性复合体中，另外两个与抗体轻链V基因有关。免疫反应基因控制免疫库，决定自身免疫性疾病的遗传风险。对于精神分裂症基于自身免疫的最简单测试是在急性病例中用泼尼松进行免疫抑制试验。迫切需要进行的研究是找到微生物触发因素，就像埃布林格对类风湿性关节炎和强直性脊柱炎所做的那样。这可能会通过接种针对触发微生物的疫苗来预防精神分裂症。
