Influence of TPH2 DNA methylation and family functioning, parenting styles on OCD severity.

Objective: The etiology of obsessive-compulsive disorder (OCD) is multifactorial and remains incompletely understood. While both the Tryptophan hydroxylase 2 (TPH2) gene and the family environment have been implicated in OCD, few studies have examined their combined effects. This study aimed to investigate the association between TPH2 DNA methylation and family functioning and parenting styles in patients with OCD.

Method: A total of 58 individuals with OCD and 89 age- and gender- matched healthy controls were recruited. DNA methylation levels at 12 CpG sites in the promoter region of TPH2 were quantified using the MassARRAY system. OCD symptom severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Parenting styles and family functioning were evaluated using the Egna Minnen Barndoms Uppfostran (EMBU) and Family Assessment Device (FAD), respectively.

Results: (1) Methylation at CpG site 6 was significantly associated with OCD status in a binary logistic regression model and remained significant after Bonferroni correction. (2) In the OCD group, CpG sites 2 and 1/3/8 showed negative correlations with the 'general functioning' and 'roles' subscales of the FAD, respectively, while CpG site 7 was positively correlated with 'affective involvement'. Methylation levels at CpG sites 2, 4, 5, 9 and 10 significantly differed based on the presence or absence of specific parenting styles in EMBU. (3) Regarding symptom severity, methylation at CpG sites 6, 9 and 12, as well as FAD dimensions (problem-solving, communication, affective responsiveness, general functioning), father's punishment, and mother's preference, were significantly associated with Y-BOCS scores.

Conclusion: DNA methylation at specific CpG sites in the TPH2 promoter region may play a critical role in the pathogenesis and symptom severity of OCD. Methylation patterns also correlated with family functioning and parenting styles. These findings suggest that TPH2 methylation may mediate the link between adverse family environments and OCD, possibly through reduced serotonin synthesis and impaired emotion regulation. Our results support a gene-environment interaction model contributing to OCD vulnerability.