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METHYLATION OF SEROTONIN RECEPTOR 3A IN ADHD, BORDERLINE PERSONALITY, AND BIPOLAR DISORDERS: LINK WITH SEVERITY OF THE DISORDERS AND CHILDHOOD MALTREATMENT
Author(s) -
Perroud Nader,
Zewdie Seblewongel,
Stenz Ludwig,
Adouan Wafae,
Bavamian Sabine,
Prada Paco,
Nicastro Rosetta,
Hasler Roland,
Nallet Audrey,
Piguet Camille,
PaoloniGiacobino Ariane,
Aubry JeanMichel,
Dayer Alexandre
Publication year - 2016
Publication title -
depression and anxiety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.634
H-Index - 129
eISSN - 1520-6394
pISSN - 1091-4269
DOI - 10.1002/da.22406
Subject(s) - bipolar disorder , borderline personality disorder , psychology , epigenetics , personality disorders , mood disorders , dna methylation , clinical psychology , methylation , psychiatry , mood , personality , genetics , anxiety , gene , biology , social psychology , gene expression
Background Serotonin 3A receptor (5‐HT 3A R) is associated at the genetic and epigenetic levels with a variety of psychiatric disorders and interacts with early‐life stress such as childhood maltreatment. We studied the impact of childhood maltreatment on the methylation status of the 5‐HT 3A R and its association with clinical severity outcomes in relation with a functional genetic polymorphism. Methods Clinical severity indexes of 346 bipolar, borderline personality, and adult attention deficit hyperactivity disorders patients were tested for association with the DNA methylation status of eight 5‐HT 3A R gene CpGs. Relationship between the functional variant rs1062613 (C > T) and methylation status on severity of the disorders were also assessed. Results Childhood maltreatment was associated with higher severity of the disease (higher number of mood episodes, history of suicide attempts, hospitalization, and younger age at onset) across disorders and within each individual disorder. This effect was mediated by two 5‐HT 3A R CpGs. Compared to T allele carriers, CC carriers had higher methylation status at one CpG located 1 bp upstream of this variant. Conclusions This study shows that epigenetic modification of the 5‐HT 3A R is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood.