Division of Psychological Medicie and Psychiatry, Section of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
Neuropsychopharmacology. 2009 Nov;34(12):2489-96. doi: 10.1038/npp.2009.77. Epub 2009 Aug 12.
Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive-compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood-brain barrier to bind against BG or other components of the OCD circuit. It is also unclear how they might lead to hyperactivity in the OCD circuit. We examined this by investigating the presence of autoantibodies directed against the BG or thalamus in the serum as well as CSF of 23 OCD patients compared with 23 matched psychiatrically normal controls using western blot. We further investigated CSF amino acid (glutamate, GABA, taurine, and glycine) levels and also examined the extent to which these levels were related to the presence of autoantibodies. There was evidence of significantly more binding of CSF autoantibodies to homogenate of BG as well as to homogenate of thalamus among OCD patients compared with controls. There was no significant difference in binding between patient and control sera except for a trend toward more bands to BG and thalamic protein corresponding to 43 kD among OCD patients compared with controls. CSF glutamate and glycine levels were also significantly higher in OCD patients compared with controls, and further multivariate analysis of variance showed that CSF glycine levels were higher in those OCD patients who had autoantibodies compared with those without. The results of our study implicate autoimmune mechanisms in the pathogenesis of OCD and also provide preliminary evidence that autoantibodies against BG and thalamus may cause OCD by modulating excitatory neurotransmission.
虽然针对基底神经节 (BG) 的血清自身抗体表明强迫症 (OCD) 的发病机制与自身免疫有关，但这些抗体是否可以穿过血脑屏障与 BG 或 OCD 回路的其他成分结合仍不清楚。它们如何导致 OCD 回路过度活跃也不清楚。我们通过使用 Western blot 法在血清和脑脊液中检查了 23 名 OCD 患者和 23 名匹配的精神病正常对照者中针对 BG 或丘脑的自身抗体的存在情况，以此来研究这个问题。我们进一步调查了 CSF 氨基酸（谷氨酸、GABA、牛磺酸和甘氨酸）水平，并研究了这些水平与自身抗体存在的关系。与对照组相比，OCD 患者的 CSF 自身抗体对 BG 匀浆和丘脑匀浆的结合明显更多。除了与对照组相比，OCD 患者的 BG 和丘脑蛋白对应于 43 kD 的蛋白的结合趋势更多外，患者和对照组血清之间的结合没有显著差异。与对照组相比，OCD 患者的 CSF 谷氨酸和甘氨酸水平也明显更高，进一步的方差分析显示，与没有自身抗体的 OCD 患者相比，具有自身抗体的 OCD 患者的 CSF 甘氨酸水平更高。我们的研究结果表明自身免疫机制参与了 OCD 的发病机制，并提供了初步证据表明针对 BG 和丘脑的自身抗体可能通过调节兴奋性神经传递导致 OCD。
