Recent findings in rat models confirmed that altered epigenetic processes, consisting in abnormal DNA methyltransferase protein levels and increased global DNA methylation levels, are linked to anxiety- and depression-like behaviour. Our finding of high levels of methylated SRD5A2 in CNS cells of a normotensive hydrocephalus individual, displaying an epigenetic status at odds with all other control subjects, further supports the link between DNA methylation pattern and disorders of the nervous system. If abnormal SRD5A2 promoter methylation is established prenatally, these subjects could be predisposed to develop the PFS and alteration of neuroactive steroid levels in the brain. In this case, treatment by finasteride might precipitate a dormant depressive phenotype linked to such specific epigenetic pattern... In conclusion, our results demonstrate methylation of SRD5A2 promoter in a tissue-specific manner in PFS patients. Whether this epigenetic pattern is established prenatally or induced by finasteride treatment cannot be concluded but this study pinpoints the relevance of this specific methylation pattern and its correlation with levels of neuroactive steroids and their effects.
Melcangi RC, Casarini L, Marino M, Santi D, Sperduti S, Giatti S, Diviccaro S, et al. Endocr Connect. 2019 Jul 1. pii: EC-19-0199.R1. doi: 10.1530/EC-19-0199. [Endocrine Connections]