Exploring the role of BDNF DNA methylation and hydroxymethylation in patients with obsessive compulsive disorder

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.