title: Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder.
abstract: Borderline personality disorder (BPD) is a complex psychiatric disease of increasing importance. Epigenetic alterations are hallmarks for altered gene expression and could be involved in the etiology of BPD. In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). DNA methylation was analyzed by bisulfite restriction analysis and pyrosequencing in whole blood samples of patients diagnosed with DSM-IV BPD and in controls. Aberrant methylation was not detectable using bisulfite restriction analysis, but a significantly increased methylation of HTR2A, NR3C1, MAOA, MAOB and soluble COMT (S-COMT) was revealed for BPD patients using pyrosequencing. For HTR2A the average methylation of four CpG sites was 0.8% higher in BPD patients compared to controls (p = 0.002). The average methylation of NR3C1 was 1.8% increased in BPD patients compared to controls (p = 0.0003) and was higher at 2 out of 8 CpGs (p ≤ 0.04). In females, an increased average methylation (1.5%) of MAOA was observed in BPD patients compared to controls (p = 0.046). A similar trend (1.4% higher methylation) was observed for MAOB in female BPD patients and increased methylation was significant for 1 out of 6 CpG sites. For S-COMT, a higher methylation of 2 out of 4 CpG sites was revealed in BPD patients (p ≤ 0.02). In summary, methylation signatures of several promoter regions were established and a significant increased average methylation (1.7%) occurred in blood samples of BPD patients (p < 0.0001). Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD.
authors.affiliation: Psychiatric Hospital, Muensterlingen, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dammann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Teschler
authors.forename: Tanja
authors.initials: T
authors.lastname: Haag
authors.forename: Franziska
authors.initials: F
authors.lastname: Altmüller
authors.forename: Frederik
authors.initials: F
authors.lastname: Tuczek
authors.forename: Reinhard H
authors.initials: RH
authors.lastname: Dammann
mesh_terms: D000328:Adult; D001883:Borderline Personality Disorder / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA