Investigating DNA Methylation in Peripheral Tissues in Borderline Personality Disorder: Association with Symptom Severity but Not Adverse Childhood Experiences.

BACKGROUND

Borderline Personality Disorder (BPD) is a complex psychiatric condition with multifactorial origins, with a high proportion of patients reporting early trauma. Stressors such as adverse childhood experiences (ACEs) can shape the epigenetic landscape including DNA methylation (DNAm) and act on gene expression. DNAm is increasingly being investigated as a molecular link between environmental exposures such as ACE and psychiatric outcomes. Differential DNAm of the gene PR domain zinc finger protein 8 (), a histone methyltransferase, has recently been reported to be sensitive to early life trauma. Its role in BPD, especially in the context of ACE, remains to be elucidated.

METHODS

This study investigated DNAm patterns of in peripheral blood and saliva obtained from BPD patients undergoing Dialectic Behavioral Therapy (DBT) compared to healthy control (HC) participants. Associations with ACE and BPD symptom severity were assessed, and therapy-related changes in DNAm were examined.

RESULTS

At baseline, BPD patients demonstrated significant hypomethylation of in blood relative to the HC group. Following DBT, a nominally significant increase in DNAm was observed, aligning with inversely correlated symptom severity. No significant differences in saliva were detected. ACE was not associated with DNAm.

CONCLUSIONS

Our findings suggest that DNAm might be associated with BPD and therapeutic intervention but not with ACE. Together with prior research, the results underscore the importance of future investigation of gene-environment interactions and the functional significance of regulation in the pathophysiology of BPD.