title: Peripartum neuroactive steroid and γ-aminobutyric acid profiles in women at-risk for postpartum depression.
abstract: Neuroactive steroids (NAS) are allosteric modulators of the γ-aminobutyric acid (GABA) system. NAS and GABA are implicated in depression. The peripartum period involves physiologic changes in NAS which may be associated with peripartum depression and anxiety. We measured peripartum plasma NAS and GABA in healthy comparison subjects (HCS) and those at-risk for postpartum depression (AR-PPD) due to current mild depressive or anxiety symptoms or a history of depression. We evaluated 56 peripartum medication-free subjects. We measured symptoms with the Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). Plasma NAS and GABA were quantified by liquid chromatography-mass spectrometry. We examined the associations between longitudinal changes in NAS, GABA and depressive and anxiety symptoms using generalized estimating equation methods. Peripartum GABA concentration was 1.9±0.7ng/mL (p=0.004) lower and progesterone and pregnanolone were 15.8±7.5 (p=0.04) and 1.5±0.7ng/mL (p=0.03) higher in AR-PPD versus HCS, respectively. HAM-D17 was negatively associated with GABA (β=-0.14±0.05, p=0.01) and positively associated with pregnanolone (β=0.16±0.06, p=0.01). STAI-S was positively associated with pregnanolone (β=0.11±0.04, p=0.004), allopregnanolone (β=0.13±0.05, p=0.006) and pregnenolone (β=0.02±0.01, p=0.04). HAM-A was negatively associated with GABA (β=-0.12±0.04, p=0.004) and positively associated with pregnanolone (β=0.11±0.05, p=0.05). Altered peripartum NAS and GABA profiles in AR-PPD women suggest that their interaction may play an important role in the pathophysiology of peripartum depression and anxiety.
authors.affiliation: Center for Psychopharmacologic Research & Treatment, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA; Women's Mental Health Program, Departments of Psychiatry and Obstetrics & Gynecology, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA 01655, USA. Electronic address: kristina.deligiannidis@umassmemorial.org.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Deligiannidis
authors.affiliation: Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: aimee.kroll@umassmed.edu.
authors.forename: Aimee R
authors.initials: AR
authors.lastname: Kroll-Desrosiers
authors.affiliation: Proteomics and Mass Spectrometry Facility and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: shunyan.mo@umassmed.edu.
authors.forename: Shunyan
authors.initials: S
authors.lastname: Mo
authors.affiliation: Proteomics and Mass Spectrometry Facility and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: hien.nguyen@umassmed.edu.
authors.forename: Hien P
authors.initials: HP
authors.lastname: Nguyen
authors.affiliation: Center for Psychopharmacologic Research & Treatment, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: abbysve@gmail.com.
authors.forename: Abby
authors.initials: A
authors.lastname: Svenson
authors.affiliation: Center for Psychopharmacologic Research & Treatment, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA; National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709-2233, USA. Electronic address: nina.jaitly@nih.gov.
authors.forename: Nina
authors.initials: N
authors.lastname: Jaitly
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709-2233, USA. Electronic address: janet.hall@nih.gov.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Hall
authors.affiliation: Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: bruce.barton@umassmed.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Barton
authors.affiliation: Center for Psychopharmacologic Research & Treatment, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: anthony.rothschild@umassmemorial.org.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Rothschild
authors.affiliation: Proteomics and Mass Spectrometry Facility and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: scott.shaffer@umassmed.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Shaffer
mesh_terms: D004092:20-alpha-Dihydroprogesterone / Q000097:blood; D000328:Adult; D016022:Case-Control Studies; D019052:Depression, Postpartum / Q000097:blood*; D003900:Desoxycorticosterone / Q000097:blood; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D058725:Peripartum Period / Q000502:physiology / Q000523:psychology; D011247:Pregnancy; D011280:Pregnanolone / Q000097:blood; D011374:Progesterone / Q000097:blood; D011963:Receptors, GABA-A / Q000097:blood; D012307:Risk Factors; D013256:Steroids / Q000097:blood*; D005680:gamma-Aminobutyric Acid / Q000097:blood*
chemical_list: D011963:Receptors, GABA-A; D013256:Steroids; D004092:20-alpha-Dihydroprogesterone; D003900:Desoxycorticosterone; D011374:Progesterone; D005680:gamma-Aminobutyric Acid; D011280:Pregnanolone
keywords: Anxiety; Depression; Neuroactive steroid; Postpartum; Pregnancy; γ-aminobutyric acid