Zakharyan Roksana, Boyajyan Anna
Institute of Molecular Biology, National Academy of Sciences of the Republic of Armenia (NAS RA), 7 Hasratyan St., 0014 Yerevan, Armenia.
Clin Biochem. 2014 Aug;47(12):1052-5. doi: 10.1016/j.clinbiochem.2014.03.021. Epub 2014 Apr 5.
A growing number of studies implicate brain-derived neurotrophic factor (BDNF), an important promoter of synaptic transmission and neural plasticity, in the pathogenesis of schizophrenia. However, the existing data are controversial, that may reflect population differences between studied groups.
In the present study we performed a comparative analysis of BDNF plasma levels and its relation with rs6265 (G196A; Val66Met) polymorphism of BDNF gene (BDNF) in schizophrenia-affected and healthy subjects (controls) of the Armenian population. To check the influence of antipsychotics on BDNF plasma levels both medicated and non-medicated patients were involved in this study. Patients with paranoid form of schizophrenia chronically treated with typical antipsychotics (n=103), age- and sex-matched controls (n=105), and 25 antipsychotic-naive first-episode schizophrenia patients were involved. The levels of BDNF in the blood plasma were measured with a solid-phase enzyme-linked immunosorbent assay.
Decreased plasma levels of BDNF in both medicated and non-medicated schizophrenia patients compared to controls were observed. No significant difference in BDNF levels between medicated and non-medicated patients was detected. It was also detected that, compared to individuals homozygous for the standard allele (G/G) of rs6265, carriers of the rs6265 minor allele (A/G+A/A), which is significantly more frequent in schizophrenia patients than in controls, had decreased BDNF levels.
The data obtained suggested that the pathogenesis of schizophrenia is characterized by genetically predetermined decreased blood levels of BDNF. These results indicated that genetically determined alterations of neuroimmune modulators may be among the risk factors of schizophrenia and contribute to disease-specific pathologic changes in functional activity of both the neuronal synaptic plasticity and the immune system.
越来越多的研究表明，脑源性神经营养因子（BDNF）作为突触传递和神经可塑性的重要促进因子，参与了精神分裂症的发病机制。然而，现有数据存在争议，这可能反映了研究组之间的人群差异。
在本研究中，我们对亚美尼亚人群中精神分裂症患者和健康对照者（对照组）的BDNF血浆水平及其与BDNF基因（BDNF）的rs6265（G196A；Val66Met）多态性的关系进行了比较分析。为了检验抗精神病药物对BDNF血浆水平的影响，本研究纳入了服用药物和未服用药物的患者。纳入了长期接受典型抗精神病药物治疗的偏执型精神分裂症患者（n = 103）、年龄和性别匹配的对照组（n = 105）以及25例未服用过抗精神病药物的首发精神分裂症患者。采用固相酶联免疫吸附测定法测量血浆中BDNF的水平。
与对照组相比，服用药物和未服用药物的精神分裂症患者的BDNF血浆水平均降低。未检测到服用药物和未服用药物的患者之间BDNF水平的显著差异。还检测到，与rs6265标准等位基因（G/G）纯合个体相比，rs6265次要等位基因（A/G + A/A）携带者的BDNF水平降低，该次要等位基因在精神分裂症患者中的频率显著高于对照组。
获得的数据表明，精神分裂症的发病机制具有基因预先决定的BDNF血液水平降低的特征。这些结果表明，神经免疫调节因子的基因决定改变可能是精神分裂症的危险因素之一，并导致神经元突触可塑性和免疫系统功能活动中特定疾病的病理变化。
