METHYLATION OF SEROTONIN RECEPTOR 3A IN ADHD, BORDERLINE PERSONALITY, AND BIPOLAR DISORDERS: LINK WITH SEVERITY OF THE DISORDERS AND CHILDHOOD MALTREATMENT.
BACKGROUND
Serotonin 3A receptor (5-HT3A 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-HT3A 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-HT3A 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-HT3A 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-HT3A R is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood.
Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland.|Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Nader
N
Perroud
Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Seblewongel
S
Zewdie
Department of Psychiatry, University of Geneva, Geneva, Switzerland.|Department of Basic Neuroscience, University of Geneva, Switzerland.
Ludwig
L
Stenz
Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Wafae
W
Adouan
Department of Psychiatry, University of Geneva, Geneva, Switzerland.|Department of Basic Neuroscience, University of Geneva, Switzerland.
Sabine
S
Bavamian
Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland.
Paco
P
Prada
Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland.
Rosetta
R
Nicastro
Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Roland
R
Hasler
Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland.
Audrey
A
Nallet
Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland.
Camille
C
Piguet
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Ariane
A
Paoloni-Giacobino
Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland.|Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Jean-Michel
JM
Aubry
Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland.|Department of Psychiatry, University of Geneva, Geneva, Switzerland.|Department of Basic Neuroscience, University of Geneva, Switzerland.
Alexandre
A
Dayer
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D001883:Borderline Personality Disorder / Q000235:genetics* / Q000523:psychology; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D012720:Severity of Illness Index
D044406:Receptors, Serotonin, 5-HT3
depression; epigenetics; methylation; mood episodes; rs1062613; serotonin receptor