Cortisol response to the Trier Social Stress Test in pregnant women at risk for postpartum depression

Antepartum depression and anxiety are risk factors for postpartum depression (PPD). Postpartum abnormalities in hypothalamic-pituitary-adrenal (HPA) reactivity are associated with PPD. It is not known if antepartum HPA abnormalities exist in women at risk for PPD (AR-PPD). We measured salivary cortisol response to the Trier Social Stress Test (TSST) in 44 (24 AR-PPD, 20 healthy comparison) pregnant women. Depression and anxiety were measured using the Edinburgh Postnatal Depression Scale (EPDS) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). We analyzed longitudinal changes in cortisol using generalized estimating equation methods to control for the correlation within subjects at the six TSST time points. Group differences in area under the curve (AUC) were examined. A majority (70.8 %) of the AR-PPD had prior depression. EPDS total score was higher in AR-PPD vs. comparison women (mean EPDS = 9.8 +/- 4.9 vs. mean EPDS = 2.4 +/- 2.0 respectively, p \u3c 0.001). Mean STAI-S total score was higher in AR-PPD vs. comparison women at all TSST time points and over time (z = 2.71, df = 1, p = 0.007). There was no significant difference in cortisol concentration over time between groups. We observed no detectable difference in cortisol response to psychosocial stress induced by the TSST despite clinically significant between-group differences in current/past depression and current symptomatology

Peripartum neuroactive steroid and gamma-aminobutyric acid profiles in women at-risk for postpartum depression

Neuroactive steroids (NAS) are allosteric modulators of the gamma-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 (beta=-0.14+/-0.05, p=0.01) and positively associated with pregnanolone (beta=0.16+/-0.06, p=0.01). STAI-S was positively associated with pregnanolone (beta=0.11+/-0.04, p=0.004), allopregnanolone (beta=0.13+/-0.05, p=0.006) and pregnenolone (beta=0.02+/-0.01, p=0.04). HAM-A was negatively associated with GABA (beta=-0.12+/-0.04, p=0.004) and positively associated with pregnanolone (beta=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