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

• Peripartum progesterone and pregnanolone concentrations were higher in at-risk women.
• Peripartum GABA concentrations were lower in at-risk women.
• Peripartum GABA concentration increased across peripartum time in both groups.

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 ± 0.7 ng/mL (p = 0.004) lower and progesterone and pregnanolone were 15.8 ± 7.5 (p = 0.04) and 1.5 ± 0.7 ng/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.