University of Teramo, Bioscience, Teramo, Italy; Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
University of Teramo, Bioscience, Teramo, Italy.
J Psychiatr Res. 2019 Jul;114:17-23. doi: 10.1016/j.jpsychires.2019.04.006. Epub 2019 Apr 6.
Obsessive-compulsive disorder (OCD) is a clinically heterogeneous neuropsychiatric condition associated with profound disability, whose susceptibility, stemming from genetic and environmental factors that intersect with each other, is still under investigation. In this perspective, we sought to explore the transcriptional regulation of Brain Derived Neurotrophic Factor (BDNF), a promising candidate biomarker in both development and etiology of different neuropsychiatric conditions, in peripheral blood mononuclear cells from OCD patients and healthy controls. In particular, we focused on BDNF gene expression and interrogated in depth DNA methylation and hydroxymethylation at gene promoters (exons I, IV and IX) in a sample of OCD patients attending a tertiary OCD Clinic to receive guidelines-recommended treatment, and matched controls. Our preliminary data showed a significant increase in BDNF gene expression and a significant correlation with changes in the two epigenetic modifications selectively at promoter exon I, with no changes in the other promoters under study. We can conclude that transcriptional regulation of BDNF in OCD engages epigenetic mechanisms, and can suggest that this is likely evoked by the long-term pharmacotherapy. It is important to underline that many different factors need to be taken into account (i.e. age, sex, duration of illness, treatment), and thus further studies are mandatory to investigate their role in the epigenetic regulation of BDNF gene. Of note, we provide unprecedented evidence for the importance of analyzing 5-hydroxymethylcytosine levels to correctly evaluate 5-methylcytosine changes.
强迫症（OCD）是一种临床异质性的神经精神疾病，与严重的残疾有关，其易感性源自遗传和环境因素的相互作用，目前仍在研究中。从这个角度来看，我们试图探索脑源性神经营养因子（BDNF）的转录调控，BDNF 是一种有前途的候选生物标志物，存在于不同神经精神疾病的发展和病因中，在 OCD 患者和健康对照者的外周血单核细胞中。特别是，我们专注于 BDNF 基因表达，并深入研究了在接受推荐治疗的 OCD 患者和匹配对照组的样本中，BDNF 基因启动子（外显子 I、IV 和 IX）的 DNA 甲基化和羟甲基化。我们的初步数据显示 BDNF 基因表达显著增加，与启动子外显子 I 中两种表观遗传修饰的变化显著相关，而在研究的其他启动子中没有变化。我们可以得出结论，OCD 中 BDNF 的转录调控涉及表观遗传机制，并且可以提示这可能是由长期药物治疗引起的。重要的是要强调，需要考虑许多不同的因素（即年龄、性别、疾病持续时间、治疗），因此需要进一步研究以调查它们在 BDNF 基因的表观遗传调控中的作用。值得注意的是，我们提供了前所未有的证据，证明分析 5-羟甲基胞嘧啶水平对于正确评估 5-甲基胞嘧啶变化非常重要。
