Blunted neuroactive steroid and HPA axis responses to stress are associated with reduced sleep quality and negative affect in pregnancy: a pilot study

• Published in: Psychopharmacology Vol. 233; no. 7; pp. 1299 - 1310
• Main Authors: Crowley, Shannon K., O’Buckley, Todd K., Schiller, Crystal E., Stuebe, Alison, Morrow, A. Leslie, Girdler, Susan S.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016; Springer; Springer Nature B.V
• Subjects: Adrenocorticotropic Hormone - metabolism; Adult; Affect - physiology; Anxiety; Behavior; Biomedical and Life Sciences; Biomedicine; Complications and side effects; Female; Health aspects; Humans; Hydrocortisone - blood; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - physiopathology; Neurosciences; Original Investigation; Pharmacology/Toxicology; Pilot Projects; Pituitary-Adrenal System - metabolism; Pituitary-Adrenal System - physiopathology; Postpartum depression; Pregnancy; Pregnanolone - blood; Progesterone - blood; Psychiatry; Psychological aspects; Sleep; Sleep - physiology; Sleep disorders; Steroids (Drugs); Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Young Adult; Pregnancy; Allopregnanolone (ALLO); Sleep; Neurosteroids; Anxiety; Postpartum depression; Cortisol; Stress
• DOI: 10.1007/s00213-016-4217-x
• ISSN: 0033-3158

Rationale Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy. Objectives Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA-ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy. Methods Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2-week subjective and objective recording of sleep-wake behavior. Results Lower cortisol, progesterone, and a combined measure of ALLO + pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated with worse sleep quality. Lower adrenocorticotropic hormone was associated with greater anxious and depressive symptoms. Stress produced paradoxical reductions in cortisol, progesterone, and a combined measure of allopregnanolone + pregnanolone, while tetrahydrodeoxycorticosterone levels were elevated. Conclusions These data suggest that cortisol, progesterone, and ALLO + pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and the negative impact of acute stress challenge appears to exert its effects by reducing these steroids to further promote negative emotional responses.