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

Abstract

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. The objective of this study was to investigate MPFC Glu levels and %GM from late pregnancy up to 7 weeks postpartum in HRW and healthy pregnant women (HPW). 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. 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). 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.

A comparative magnetic resonance spectroscopy study of GABA+ and glutamate referenced to creatine and phosphocreatine in the left dorsolateral prefrontal cortex of perimenopausal women and women of reproductive age

“…A limitation of this study was that sample sizes were relatively small for both PM ( n = 18) and RD ( n = 20) groups. However, we were able to show decreased GABA+ and/or Glu ratios in similar or smaller samples that investigated the impact of reproductive status on these metabolites ( 3 , 18 , 33 ). We do not believe that our negative results are explained by a small sample size and therefore by a type II error.…”

“…However, Cr+PCr have been used extensively as a reference molecule in previous MRS MD research ( 42 ). In addition, our group recently demonstrated that Cr+PCr was unaffected by the large female hormone changes experienced during pregnancy and postpartum ( 33 , 43 ). Together, these findings indicate that Cr+PCr is a viable reference molecule for MRS research in PM women.…”

“…Statistical Parametric Mapping (SPM12) ( 33 ) were used for T1 image volumetric and segmentation analysis. Included in Gannet package pipeline were steps to generate a mask of the MRS voxel in T1-image space and to utilize the SPM12 “Segmentation” function to calculate relative GM, WM, and CSF fractions within MPFC voxel (later referenced to as %GM, %WM, and %CSF).…”

Assessing the risk of prenatal depressive symptoms in Chinese women: an integrated evaluation of serum metabolome, multivitamin supplement intake, and clinical blood indicators

“…Some amino acids and their precursors act as the neurotransmitters in the regulation of depressive symptoms. For example, glutamate, an important excitatory neurotransmitter, is usually observed at low levels in the prefrontal cortex of women with late pregnancy or postpartum depression ( 19 ). It can be restored in the dorsolateral prefrontal cortex after progesterone treatment ( 23 ).…”

Structural, functional, and metabolic signatures of postpartum depression: A systematic review

“…The perinatal period alone is associated with substantial changes in the brain connectivity and structural integrity in healthy mothers, as their brains undergo the process of adaptation to the maternal caregiving ( 12 , 13 ). Considering these essential transformations, it is of interest to examine whether the PPD brain features differ from those observed in a non-depressed peripartum mother.…”