Background: Patients suffering from schizophrenic psychosis show reduced synaptic connectivity compared to healthy individuals. Furthermore, the use of cannabis often precedes the onset of schizophrenic psychosis. Therefore, we investigated whether consumption of cannabis has an impact on the methylation pattern of schizophrenia candidate genes concerned with the development and preservation of synapses and synaptic function. Methods: Fifty blood samples of outpatients affected by treatment-resistant schizophrenic psychosis were collected in the outpatient department of Ch Ste Anne/INSERM (Paris, France). Extracted DNA was sent to the LMN/MHH (Hanover, Germany) where DNA samples were bisulfite converted. The methylation patterns of the promoter region of neuregulin 1 (NRG1), neurexin (NRXN1), disrupted in schizophrenia 1 (DISC1), and microtubule-associated-protein tau (MAPT) were then analysed by sequencing according to Sanger. Results: In NRXN1 the group of non-consumer patients showed a methylation rate slightly lower than controls. In patients with preliminary use of tetrahydrocannabinol (THC) the NRXN1 promoter turned out to be methylated almost two times higher than in non-consumer patients. In MAPT, non-consumer patients showed a significant lower mean methylation rate in comparison to controls. In THC-consuming patients the difference compared with controls became less. NRG1 and DISC1 showed no significant differences between groups, whereas DISC1 appeared to be not methylated at all. Conclusion: In MAPT and NRXN1 mean methylation rates were lower in non-consumer patients compared with controls, which seems to be a compensatory mechanism. With consumption of THC, mean methylation rates were increased: in the case of MAPT compared with controls, and in NRXN1 even significantly beyond that. Methylation of NRG1 and DISC1 seems not to be affected by the psychiatric disorder or by consumption of THC.
Neuropsychobiology

中文翻译：

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与非消费患者和健康对照相比，服用四氢大麻酚的抗药性精神分裂症患者的精神分裂症候选基因的差异甲基化模式。

背景：与健康个体相比，患有精神分裂症的精神病患者的突触连接性降低。此外，大麻的使用通常先于精神分裂症精神病的发作。因此，我们调查了大麻的消费是否对与突触和突触功能的发育和保存有关的精神分裂症候选基因的甲基化模式有影响。方法：在 Ch Ste Anne/INSERM（法国巴黎）门诊部收集了 50 份患有难治性精神分裂症精神病的门诊患者的血液样本。提取的 DNA 被送到 LMN/MHH（德国汉诺威），在那里 DNA 样品被亚硫酸氢盐转化。神经调节蛋白 1 ( NRG1)启动子区的甲基化模式)、神经蛋白 ( NRXN1 )、在精神分裂症 1 中被破坏 ( DISC1 ) 和微管相关蛋白 tau ( MAPT ) 然后根据 Sanger 通过测序进行分析。结果：在NRXN1中，非消费患者组的甲基化率略低于对照组。在初步使用四氢大麻酚 (THC) 的患者中，NRXN1启动子的甲基化率几乎是非消费患者的两倍。在MAPT 中，与对照组相比，非消费患者的平均甲基化率显着降低。在使用 THC 的患者中，与对照组相比差异变小。NRG1和DISC1在组间没有显着差异，而DISC1似乎根本没有甲基化。结论：在MAPT和NRXN1中，非消费患者的平均甲基化率低于对照组，这似乎是一种补偿机制。随着 THC 的消耗，平均甲基化率增加：在MAPT的情况下，与对照相比，在NRXN1 中甚至显着超过了这一点。NRG1和DISC1 的甲基化似乎不受精神疾病或 THC 消耗的影响。
神经心理生物学