Integrative DNA Methylation and Gene Expression Analysis of Cognitive Behavioral Therapy Response in Children and Adolescents with Obsessive-Compulsive Disorder; a Pilot Study

PURPOSE: Here, we propose an integrative analysis of genome-wide methylation and gene expression to provide new insight into the biological mechanisms of Cognitive behavioral therapy (CBT) in pediatric obsessive-compulsive disorder (OCD). PATIENTS AND METHODS: Twelve children and adolescents with OCD receiving CBT for the first time were classified as responders or non-responders after eight weeks of CBT. Differentially methylated positions (DMPs) and gene co-expression modules were identified using specific R software packages. Correlations between the DMPs and gene co-expression modules were investigated. RESULTS: Two genes were enriched with significant DMPs (Δβ > ± 0.2, FDR-adjusted p-value < 0.05): PIWIL1 and MIR886. The yellowgreen module of co-expressed genes was associated with CBT response (FDR-adjusted p-value = 0.0003). Significant correlations were observed between the yellowgreen module and the CpGs in PIWIL1 and MIR886 (p < 0.008). Patients showing hypermethylation in these CpGs presented an upregulation in the genes in the yellowgreen module. CONCLUSION: Taken together, the preliminary results of this systems-level approach, despite the study limitations, provide evidence that the epigenetic regulation of ncRNAs could be a predictor of CBT response. LIMITATIONS: The sample size limited the statistical power, and given that the study was hypothesis-driven, our results should be seen as preliminary.