Arnold Paul D, Rosenberg David R, Mundo Emanuela, Tharmalingam Subi, Kennedy James L, Richter Margaret A
Child Psychiatry Program, Neurogenetics Section, 1st Floor, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8.
Psychopharmacology (Berl). 2004 Aug;174(4):530-8. doi: 10.1007/s00213-004-1847-1. Epub 2004 Apr 9.
Recent investigation suggests that a reversible glutamatergically mediated thalamocortical-striatal dysfunction may serve as a reliable pathophysiological and treatment response marker for obsessive-compulsive disorder (OCD). We postulated that N-methyl- d-aspartate (NMDA) receptors were involved in OCD, and specifically that polymorphisms in the 3' untranslated region of GRIN2B (glutamate receptor, ionotropic, N-methyl- d-aspartate 2B) were associated with OCD in affected families.
The objective of this investigation was to test the association between GRIN2B variants and transmission of the OCD trait using a family-based design.
Using the Family Based Association Test (FBAT), we tested for association with OCD diagnosis in 130 families, and also performed a haplotype analysis. FBAT was additionally used in a subset of 98 families to test for association with the quantitative phenotype of lifetime OCD symptom severity. RESULTS. Under a non-additive model of inheritance, the 5072T/G variant was significantly associated with OCD even after correcting for the number of models tested ( P=0.014). In addition, there was a significant positive association with OCD diagnosis ( P=0.002) for the 5072G-5988T haplotype under the recessive model.
Although preliminary and requiring replication in larger samples, these results provide evidence that GRIN2B may be associated with susceptibility to OCD. Coupled with basic neuroscience and clinical neuroimaging findings in patients with OCD, our results provide new and converging support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.
最近的研究表明，一种可逆的谷氨酸能介导的丘脑皮质 - 纹状体功能障碍可能是强迫症（OCD）可靠的病理生理和治疗反应标志物。我们推测N - 甲基 - D - 天冬氨酸（NMDA）受体与强迫症有关，特别是GRIN2B（离子型谷氨酸受体，N - 甲基 - D - 天冬氨酸2B）3'非翻译区的多态性与受影响家庭中的强迫症有关。
本研究的目的是使用基于家系的设计来测试GRIN2B变异与强迫症特征传递之间的关联。
我们使用基于家系的关联测试（FBAT），在130个家庭中测试与强迫症诊断的关联，并进行单倍型分析。另外，在98个家庭的子集中使用FBAT来测试与终身强迫症症状严重程度的定量表型的关联。结果。在非加性遗传模型下，即使校正测试模型的数量后，5072T/G变异与强迫症仍显著相关（P = 0.014）。此外，在隐性模型下，5072G - 5988T单倍型与强迫症诊断有显著正相关（P = 0.002）。
尽管这些结果是初步的且需要在更大样本中重复验证，但它们提供了证据表明GRIN2B可能与强迫症易感性有关。结合强迫症患者的基础神经科学和临床神经影像学发现，我们的结果为谷氨酸能神经传递改变在强迫症发病机制中的作用提供了新的和一致的支持。
