title: BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample.
abstract: It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF) signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study examines the link between methylation of the BDNF gene promoter region and patterns of neural activity that are associated with maternal response to stressful versus non-stressful child stimuli within a sample that includes mothers with interpersonal violence-related PTSD (IPV-PTSD). 46 mothers underwent fMRI. The contrast of neural activity when watching children-including their own-was then correlated to BDNF methylation. Consistent with the existing literature, the present study found that maternal BDNF methylation was associated with higher levels of maternal anxiety and greater childhood exposure to domestic violence. fMRI results showed a positive correlation of BDNF methylation with maternal brain activity in the anterior cingulate (ACC), and ventromedial prefrontal cortex (vmPFC), regions generally credited with a regulatory function toward brain areas that are generating emotions. Furthermore we found a negative correlation of BDNF methylation with the activity of the right hippocampus. Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between vmPFC/ACC activity and BDNF methylation may be linked to mothers who are at a disadvantage with respect to emotion regulation when facing stressful parenting situations. Overall, this study provides evidence that epigenetic signatures of stress-related genes can be linked to functional brain regions regulating parenting stress, thus advancing our understanding of mothers at risk for stress-related psychopathology.
authors.affiliation: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Dominik A
authors.initials: DA
authors.lastname: Moser
authors.affiliation: Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Paoloni-Giacobino
authors.affiliation: Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Stenz
authors.affiliation: Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Wafae
authors.initials: W
authors.lastname: Adouan
authors.affiliation: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Manini
authors.affiliation: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Suardi
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: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Marylene
authors.initials: M
authors.lastname: Vital
authors.affiliation: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: Sancho Rossignol
authors.affiliation: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rusconi-Serpa
authors.affiliation: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Ansermet
authors.affiliation: Faculty of Health, Psychology and Social care, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: Alexandre G
authors.initials: AG
authors.lastname: Dayer
authors.affiliation: Department of Child & Adolescent Psychiatry, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Schechter
mesh_terms: D000328:Adult; D001007:Anxiety; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002675:Child, Preschool; D019175:DNA Methylation; D017579:Domestic Violence; D044127:Epigenesis, Genetic; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D009035:Mothers / Q000523:psychology; D011401:Promoter Regions, Genetic; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human