title: Prenatal Major Depressive Disorder, Placenta Glucocorticoid and Serotonergic Signaling, and Infant Cortisol Response.
abstract: Extending prior studies of prenatal adversity and depressive symptoms, we tested associations between maternal prenatal major depressive disorder (MDD) and infant cortisol regulation. Based on prior findings by our group, we also tested placenta glucocorticoid (HSD11B2 methylation) and serotonin (SLC6A4 gene expression) signaling as moderators of links between prenatal MDD and infant cortisol.
  
  
  
  Participants were 153 mother-infant pairs from a low-income, diverse sample (M [SD] age = 26 [6] years). Repeated structured diagnostic interviews were used to identify mothers with (a) prenatal MDD, (b) preconception-only MDD, and (c) controls. Placenta samples were assayed for HSD11B2 methylation and SLC6A4 gene expression. Infant salivary cortisol response to a neurobehavioral examination was assessed at 1 month.
  
  
  
  Daughters of prenatal MDD mothers had 51% higher baseline (ratio = 1.51; 95% confidence interval [CI] = 1.01-2.27; p = .045) and 64% higher stress responsive cortisol (ratio = 1.64; 95% CI = 1.05-2.56; p = .03) than daughters of controls and 75% higher stress-responsive cortisol (ratio = 1.75; 95% CI = 1.04-2.94; p = .04) than daughters of preconception-only MDD mothers. HSD11B2 methylation moderated links between prenatal MDD and baseline cortisol (p = .02), with 1% methylation decreases associated with 9% increased baseline cortisol in infants of prenatal MDD mothers (ratio = 1.09; 95% CI = 1.01-1.16). SLC6A4 expression moderated links between prenatal MDD and cortisol response among boys alone (p = .007), with 10-fold increases in expression associated with threefold increases in stress-responsive cortisol (ratio = 2.87; 95% CI = 1.39-5.93) in sons of control mothers.
  
  
  
  Results highlight specificity of associations between prenatal versus preconception MDD and cortisol regulation and the importance and complexity of placenta glucocorticoid and serotonergic pathways underlying the intergenerational transmission of risk from maternal adversity.
authors.affiliation: From the Department of Psychiatry and Human Behavior (Stroud, Parade, Salisbury, Lester), Warren Alpert Medical School, Brown University; Providence, Rhode Island; Centers for Behavioral and Preventive Medicine (Stroud), The Miriam Hospital, Providence, Rhode Island; Department of Biostatistics, School of Public Health (Papandonatos), Brown University, Providence, Rhode Island; Bradley/Hasbro Children's Research Center (Parade), Providence, Rhode Island; Department of Pediatrics (Salisbury, Lester, Padbury), Warren Alpert Medical School, Brown University, Providence, Rhode Island; Women & Infants' Hospital of Rhode Island (Salisbury, Phipps, Lester, Padbury), Providence, Rhode Island; Department of Obstetrics and Gynecology (Phipps), Warren Alpert Medical School, Brown University, Providence, Rhode Island; and Department of Environmental Health (Marsit), Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Stroud
authors.forename: George D
authors.initials: GD
authors.lastname: Papandonatos
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Parade
authors.forename: Amy L
authors.initials: AL
authors.lastname: Salisbury
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Phipps
authors.forename: Barry M
authors.initials: BM
authors.lastname: Lester
authors.forename: James F
authors.initials: JF
authors.lastname: Padbury
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000328:Adult; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007223:Infant; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D012463:Saliva; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction; D013315:Stress, Psychological / Q000378:metabolism*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D006854:Hydrocortisone