Prospective Investigation of Glutamate Levels and Percentage Gray Matter in the Medial Prefrontal Cortex in Females at Risk for Postpartum Depression

Curr Neuropharmacol. 2022;20(10):1988-2000. doi: 10.2174/1570159X20666220302101115.


Background: The substantial female hormone fluctuations associated with pregnancy and postpartum have been linked to a greater risk of developing depressive symptoms, particularly in high-risk women (HRW), i.e. those with histories of mood sensitivity to female hormone fluctuations. We have shown that glutamate (Glu) levels in the medial prefrontal cortex (MPFC) decrease during perimenopause, a period of increased risk of developing a major depressive episode. Our team has also demonstrated that percentage gray matter (%GM), another neural correlate of maternal brain health, decreases in the MPFC during pregnancy.

Objective: To investigate MPFC Glu levels and %GM from late pregnancy up to 7 weeks postpartum in HRW and healthy pregnant women (HPW).

Methods: Single-voxel spectra were acquired from the MPFC of 41 HPW and 22 HRW using 3- Tesla in vivo proton magnetic resonance spectroscopy at five different time points.

Results: We observed a statistically significant interaction between time and group for the metabolite Glu, with Glu levels being lower for HRW during pregnancy and early postpartum (p<0.05). MPFC %GM was initially lower during pregnancy and then significantly increased over time in both groups (p<0.01).

Conclusion: This investigation suggests that the vulnerability towards PPD is associated with unique fluctuations of MPFC Glu levels during pregnancy and early postpartum period. Our results also suggest that the decline in MPFC %GM associated with pregnancy seems to progressively recover over time. Further investigations are needed to determine the specific role that female hormones play on the physiological changes in %GM during pregnancy and postpartum.

Keywords: Glutamate; depression; gray matter; magnetic resonance spectroscopy; postpartum; pregnancy.

MeSH terms

  • Depression, Postpartum* / metabolism
  • Depressive Disorder, Major* / metabolism
  • Female
  • Glutamic Acid / metabolism
  • Gray Matter / diagnostic imaging
  • Gray Matter / metabolism
  • Hormones / metabolism
  • Humans
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / metabolism
  • Pregnancy
  • Prospective Studies


  • Hormones
  • Glutamic Acid