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

Abstract

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.

Keywords: Allopregnanolone (ALLO); Anxiety; Cortisol; Neurosteroids; Postpartum depression; Pregnancy; Sleep; Stress.

Figure 1

Schematic representation of stress testing protocol: ^aCardiovascular measures [heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP)] were collected (1) every two minutes during the last 10-min of the venipuncture recovery period; (2) at the beginning of the speech preparation period; (3) at the beginning and at minute two of the speech task; (4) every two minutes of the PASAT task; and (5) every five minutes of the first 20 minutes of the post-stress recovery period. These measures were then averaged to obtain a mean speech preparation, speech, and PASAT task value for each cardiovascular measure. ^bBlood for cortisol was collected at the end of venipuncture recovery and again 10, 20, 30, and 40 minutes post-stressor completion. ^cBlood for adrenocorticotrophic hormone (ACTH) was collected (1) at the end of venipuncture recovery; (2) immediately following stressor completion (after the PASAT task); and (3) 10 and 20 minutes post-stressor completion. Blood for ^dprogesterone (PROG) and neurosteroids [ALLO, Pregnanolone, 3α,5β-THDOC (THDOC)] was collected (1) at the end of venipuncture recovery period; (2) minute two of the speech task; (3) immediately following stressor completion (after the PASAT task); and (4) 10, 20, 30, and 40 minutes post-stressor completion.

Figure 2

Scatterplot and regression line reflecting Pearson correlation (r) of Cortisol AUG_G and (A) mean actigraphy-measured wake after sleep onset (WASO) duration (in minutes); and (B) anxiety in response to the Paced Auditory Serial Addition Task (PASAT)

Figure 3

Time course of the ALLO + pregnanolone combined measure stress response in second trimester pregnant women, measured via GC-MS. Data represent mean ± SEM as a function of time across the task. ^aSample taken during minute 2 of the speech task. ^bSample taken immediately following the PASAT task. **p ≤ 0.05

Figure 4

Time course of 3,5β–THDOC stress response in second trimester pregnant women, measured via GC-MS. Data represent mean ± SEM as a function of time across the task. ^aSample taken during minute 2 of the speech task. ^bSample taken immediately following the PASAT task. *p ≤ 0.01; ** p ≤ 0.05