Exploring the Influence of DNA Methylation and family factors on OCD and symptoms Severity: Insights into the TPH2 Gene

Abstract

Abstract Objective: The etiology of obsessive-compulsive disorder (OCD) remains incompletely understood. Previous studies have implicated the TPH2 gene and several family factors in OCD. This study aimed to investigate the correlation of TPH2 gene methylation and family factors (parenting styles and family functioning) on OCD and its clinical severity. Method: A total of 88 patients with OCD and 94 healthy controls were enrolled. DNA methylation levels at twelve sites in the promoter region of the TPH2 gene were measured using DNA inflight mass spectrometry system and polymerase chain reaction (PCR). The severity of OCD symptoms was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Egna Minnen Barndoms Uppfostran (EMBU) and Family Assessment Device (FAD) scales were used to measure parenting styles and family functioning, respectively. Results: DNA methylation levels of CpG site 5 were negatively correlated, and site 6 was positively associated with the onset of OCD. Further analysis revealed a positive association between DNA methylation level at CpG site 5 and a paternal-favoring parenting style as measured by the EMBU in OCD. Additionally, DNA methylation levels at CpG site 2 were positively correlated with maternal emotional warmth of EMBU but negatively correlated with the general functioning of FAD; they were also negatively correlated with compulsive behavior scores and total scores of Y-BOCS. DNA methylation levels at CpG site 1,3,8 were negatively associated with maternal emotional warmth of EMBU while positively correlated with compulsive behavior scores and total scores of Y-BOCS. Moreover, DNA methylation levels of CpG site 9, 10 and 12 were positively associated with problem-solving, total scores of Y-BOCS, and maternal emotional warmth, respectively. Obsessive thoughts were found to be negatively associated only with paternal emotional warmth of EMBU. Conclusion: DNA methylation at different CpG sites in the promoter region of the TPH2 gene may play critical roles in the onset and progression of OCD. Parenting styles and family functioning could impact the progression of the disease, and the DNA methylation of the TPH2 gene may mediated the effect of family factors on OCD.