Damion J Grasso1, Stacy Drury2, Margaret Briggs-Gowan3, Amy Johnson4, Julian Ford3, Garry Lapidus5, Victoria Scranton3, Christine Abreu6, Jonathan Covault3. 1. Department of Psychiatry, University of Connecticut School of Medicine, United States. Electronic address: dgrasso@uchc.edu. 2. Psychiatry and Behavioral Sciences, Tulane University School of Medicine, United States. 3. Department of Psychiatry, University of Connecticut School of Medicine, United States. 4. Obstetrics & Gynecology, Hartford Hospital, United States. 5. Department of Pediatrics and Community Medicine, University of Connecticut School of Medicine and Connecticut Children's Medical Center, United States. 6. Clinical Research Center, University of Connecticut School of Medicine, United States.
Abstract
BACKGROUND: Genetic variation and epigenetic mechanisms involving the stress-related gene FKBP5 have been implicated in the intergenerational transmission of trauma-related effects in adult offspring of trauma-exposed caregivers, but these processes have not been fully explored in postpartum women and their newborn infants. METHODS: Women recruited from a prenatal care clinic during their third trimester of pregnancy (N = 114) completed a battery of instruments assessing adverse childhood experiences (ACEs), adversity in adulthood, posttraumatic stress disorder (PTSD) symptoms, negative emotional state, and emotion dysregulation. FKBP5 rs1360780 genotype and intron 7 methylation were derived from saliva collected from postpartum mothers and their newborn infants within 24 h of delivery. RESULTS: Allele-specific associations of methylation with maternal ACEs and prenatal trauma-related symptoms were evident; however, relations differed between mothers and newborns. In mothers carrying the stress sensitive T-allele (CT and TT genotypes), maternal FKBP5 methylation negatively correlated with threat-based ACEs and maternal PTSD symptoms during pregnancy, but not deprivation-based ACEs. In infants homozygous for the C allele (CC genotype), infant FKBP5 methylation positively correlated with maternal threat-based ACEs and prenatal PTSD symptom severity, but not deprivation-based ACEs or adversity in adulthood. CONCLUSIONS: Our results provide evidence that links maternal threat-based ACEs and trauma-related symptoms during pregnancy with allele-specific epigenetic patterns in postpartum women and their newborn infants. These findings provide mechanistic insight into the potential intergenerational impact of ACEs and the effect of maternal PTSD symptoms during pregnancy.
BACKGROUND: Genetic variation and epigenetic mechanisms involving the stress-related gene FKBP5 have been implicated in the intergenerational transmission of trauma-related effects in adult offspring of trauma-exposed caregivers, but these processes have not been fully explored in postpartum women and their newborn infants. METHODS:Women recruited from a prenatal care clinic during their third trimester of pregnancy (N = 114) completed a battery of instruments assessing adverse childhood experiences (ACEs), adversity in adulthood, posttraumatic stress disorder (PTSD) symptoms, negative emotional state, and emotion dysregulation. FKBP5rs1360780 genotype and intron 7 methylation were derived from saliva collected from postpartum mothers and their newborn infants within 24 h of delivery. RESULTS: Allele-specific associations of methylation with maternal ACEs and prenatal trauma-related symptoms were evident; however, relations differed between mothers and newborns. In mothers carrying the stress sensitive T-allele (CT and TT genotypes), maternal FKBP5 methylation negatively correlated with threat-based ACEs and maternal PTSD symptoms during pregnancy, but not deprivation-based ACEs. In infants homozygous for the C allele (CC genotype), infantFKBP5 methylation positively correlated with maternal threat-based ACEs and prenatal PTSD symptom severity, but not deprivation-based ACEs or adversity in adulthood. CONCLUSIONS: Our results provide evidence that links maternal threat-based ACEs and trauma-related symptoms during pregnancy with allele-specific epigenetic patterns in postpartum women and their newborn infants. These findings provide mechanistic insight into the potential intergenerational impact of ACEs and the effect of maternal PTSD symptoms during pregnancy.
Authors: Vasiliki Michopoulos; Alex O Rothbaum; Elizabeth Corwin; Bekh Bradley; Kerry J Ressler; Tanja Jovanovic Journal: Arch Womens Ment Health Date: 2014-10-03 Impact factor: 3.633
Authors: Adam Bryant Miller; Margaret A Sheridan; Jamie L Hanson; Katie A McLaughlin; John E Bates; Jennifer E Lansford; Gregory S Pettit; Kenneth A Dodge Journal: J Abnorm Psychol Date: 2018-02
Authors: Rachel Yehuda; Nikolaos P Daskalakis; Linda M Bierer; Heather N Bader; Torsten Klengel; Florian Holsboer; Elisabeth B Binder Journal: Biol Psychiatry Date: 2015-08-12 Impact factor: 13.382
Authors: Torsten Klengel; Divya Mehta; Christoph Anacker; Monika Rex-Haffner; Jens C Pruessner; Carmine M Pariante; Thaddeus W W Pace; Kristina B Mercer; Helen S Mayberg; Bekh Bradley; Charles B Nemeroff; Florian Holsboer; Christine M Heim; Kerry J Ressler; Theo Rein; Elisabeth B Binder Journal: Nat Neurosci Date: 2012-12-02 Impact factor: 24.884
Authors: Kai MacDonald; Michael L Thomas; Andres F Sciolla; Beacher Schneider; Katherine Pappas; Gijs Bleijenberg; Martin Bohus; Bradley Bekh; Linda Carpenter; Alan Carr; Udo Dannlowski; Martin Dorahy; Claudia Fahlke; Ricky Finzi-Dottan; Tobi Karu; Arne Gerdner; Heide Glaesmer; Hans Jörgen Grabe; Marianne Heins; Dianna T Kenny; Daeho Kim; Hans Knoop; Jill Lobbestael; Christine Lochner; Grethe Lauritzen; Edle Ravndal; Shelley Riggs; Vedat Sar; Ingo Schäfer; Nicole Schlosser; Melanie L Schwandt; Murray B Stein; Claudia Subic-Wrana; Mark Vogel; Katja Wingenfeld Journal: PLoS One Date: 2016-01-27 Impact factor: 3.240
Authors: Błażej Misiak; Paweł Karpiński; Elżbieta Szmida; Tomasz Grąźlewski; Marcin Jabłoński; Katarzyna Cyranka; Joanna Rymaszewska; Patryk Piotrowski; Kamila Kotowicz; Dorota Frydecka Journal: J Clin Med Date: 2020-11-24 Impact factor: 4.241
Authors: Cheryl Buehler; Savannah A Girod; Esther M Leerkes; Lauren Bailes; Lenka H Shriver; Laurie Wideman Journal: Womens Health Rep (New Rochelle) Date: 2022-06-13