title: The association of serotonin receptor 3A methylation with maternal violence exposure, neural activity, and child aggression.
abstract: Methylation of the serotonin 3A receptor gene (HTR3A) has been linked to child maltreatment and adult psychopathology. The present study examined whether HTR3A methylation might be associated with mothers' lifetime exposure to interpersonal violence (IPV), IPV-related psychopathology, child disturbance of attachment, and maternal neural activity.
  
  
  
  Number of maternal lifetime IPV exposures and measures of maternal psychopathology including posttraumatic stress disorder (PTSD), major depression and aggressive behavior (AgB), and a measure of child attachment disturbance known as "secure base distortion" (SBD) were assessed in a sample of 35 mothers and children aged 12-42 months. Brain fMRI activation was assessed in mothers using 30-s silent film excerpts depicting menacing adult male-female interactions versus prosocial and neutral interactions. Group and continuous analyses were performed to test for associations between clinical and fMRI variables with DNA methylation.
  
  
  
  Maternal IPV exposure-frequency was associated with maternal PTSD; and maternal IPV-PTSD was in turn associated with child SBD. Methylation status of several CpG sites in the HTR3A gene was associated with maternal IPV and IPV-PTSD severity, AgB and child SBD, in particular, self-endangering behavior. Methylation status at a specific CpG site (CpG2_III) was associated with decreased medial prefrontal cortical (mPFC) activity in response to film-stimuli of adult male-female interactions evocative of violence as compared to prosocial and neutral interactions.
  
  
  
  Methylation status of the HTR3A gene in mothers is linked to maternal IPV-related psychopathology, trauma-induced brain activation patterns, and child attachment disturbance in the form of SBD during a sensitive period in the development of self-regulation.
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland. Electronic address: daniel.schechter@hcuge.ch.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Schechter
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Dominik A
authors.initials: DA
authors.lastname: Moser
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Virginie C
authors.initials: VC
authors.lastname: Pointet
authors.affiliation: Institute of Psychology, University of Bern, Bern, Switzerland.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Aue
authors.affiliation: Department of Mental Health and Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Stenz
authors.affiliation: Department of Genetic Medecine and Development, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Paoloni-Giacobino
authors.affiliation: Department of Mental Health and Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Wafae
authors.initials: W
authors.lastname: Adouan
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Manini
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Suardi
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Marylene
authors.initials: M
authors.lastname: Vital
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: Sancho Rossignol
authors.affiliation: Faculty of Health, Psychology and Social Care, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Cordero
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Molly
authors.initials: M
authors.lastname: Rothenberg
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Ansermet
authors.affiliation: Division of Child & Adolescent Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rusconi Serpa
authors.affiliation: Department of Mental Health and Psychiatry, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland; Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
authors.forename: Alexandre G
authors.initials: AG
authors.lastname: Dayer
mesh_terms: D000328:Adult; D000069586:Adult Survivors of Child Adverse Events / Q000523:psychology*; D000374:Aggression / Q000502:physiology*; D002652:Child Behavior / Q000502:physiology*; D002675:Child, Preschool; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000503:physiopathology; D000069581:Exposure to Violence / Q000523:psychology*; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009769:Object Attachment; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D000068356:Self-Control; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology*
chemical_list: C509409:HTR3A protein, human; D044406:Receptors, Serotonin, 5-HT3
keywords: Attachment disorder; Epigenetics; Interpersonal violence; Maternal posttraumatic stress disorder (PTSD); Serotonin receptor; fMRI