Glutamate levels in the medial prefrontal cortex of healthy pregnant women compared to non-pregnant controls

et al. 2022

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.

Section: Discussionsupporting

confidence: 91%

“…A full description of the methods used to obtain 1 H-MRS data in this study can be found in our previous work [ 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Ghuman

McEwen

et al. 2022

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Luki²,

Hanstock³

et al. 2022

Front. Psychiatry

ObjectiveThe perimenopause is associated with an increased risk of developing a major depressive (MD) episode. The biological changes occurring during perimenopause responsible for this increased risk of depression remain to be elucidated. Postmortem and magnetic resonance spectroscopy (MRS) studies have revealed decreased gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the dorsolateral prefrontal cortex (DLPFC) of MD patients. The objective of this study was to compare LDLPFC GABA+ and Glu ratios (referenced to creatine and phosphocreatine) in healthy reproductive-aged (RD) and perimenopausal (PM) women.Materials and methodsEighteen healthy PM and 20 RD women were included in the study. Our dependent variables, LDLPFC Glu and GABA+ ratios which include homocarnosine and macromolecules, were measured via MRS, using a 3 Tesla magnet. Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle (MC). PM women were scanned outside of ovulatory cycles.ResultsMean LDLPFC GABA+ and Glu ratios were not statistically different between the PM group and RD group (PM mean = 0.10 ± 0.06, RD mean = 0.11 ± 0.04, t = –0.383, df = 36, d = −0.13, p = 0.70) (PM mean = 0.56 ± 0.06, RD mean = 0.57 ± 0.05, t = –0.794, df = 36, d = −0.26, p = 0.43), respectively. The perimenopause demarcates the end of the reproductive life. Unsurprisingly PM women were older than RD women (PM women: 48.8 ± 3.55 years, range 41–53 years old; RD women: 31.5 ± 9.66 years, range 18–47 years old) (p < 0.001). This inherent entanglement of group and age is a limitation of our study.ConclusionContrary to our previous findings of decreased GABA+ and Glu in the medial prefrontal cortex in perimenopausal women, the perimenopause is not associated with decreased GABA+ or Glu ratios in the LDLPFC. This suggests that brain areas playing a role in MD display different sensitivity to the female hormones fluctuations associated with perimenopause.

Decreased GABA+ Levels in the Medial Prefrontal Cortex of Perimenopausal Women: A 3T 1H-MRS Study

International Journal of Neuropsychopharmacology

Luki

Hanstock

et al. 2022

Objective Perimenopause is associated with an increased risk of developing a major depressive (MD) episode. A significant number of women develop their first MD episode during perimenopause, suggesting a unique pathophysiology of perimenopausal depression. Previous research has shown that depression is associated with decreased gamma-aminobutyric acid (GABA) levels in the medial prefrontal cortex (MPFC) of MD patients. The objective of this study was to compare MPFC GABA+ levels in healthy reproductive-aged (RD) and perimenopausal (PM) women. Methods 18 healthy PM and 20 RD women were included in the study. MPFC GABA+ levels which include homocarnosine and macromolecules were measured via Magnetic Resonance Spectroscopy (MRS), using a 3 Tesla magnet. MPFC GABA+ levels were reference to creatine + phosphocreatine (Cr+PCr). Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle (MC). PM women were scanned outside of ovulatory cycles. Results Mean MPFC GABA+ concentrations (relative to Cr+PCr) were decreased in the PM group compared to RD group PM mean = 0.08 ± 0.02, RD mean = 0.09 ± 0.02, t = –2.03, df = 36, p = 0.05) even after correcting for % in GM. PM women being inherently older than RD women (48.8 ± 3.55 and 31.5 ± 9.66 years old respectively), the age difference between the 2 groups was statistically significant (p<0.001). When age was treated as an independent co-variate and included in the model, the difference in GABA+ between PM and RD women was not significant anymore (p = 0.092). Conclusion Perimenopause is associated with decreased MPFC GABA+/Cr+PCr levels which may be contributing to the increased risk of experiencing a MD episode during PM.