Decreased Medial Prefrontal Cortex Glutamate Levels in Perimenopausal Women.

Sidney Yap,Christopher C Hanstock,Huaying (Helen) Zhao,Jessica Luki,Alynna Lirette,Katherine J Aitchison,Peter Seres,Tami Shandro,Jean-Michel Le Melledo,Sarah E C Hanstock

doi:10.3389/fpsyt.2021.763562

Abstract

Objective: There is an increased risk of experiencing depression during perimenopause (PM), a period of rapidly changing female hormone concentrations. Women at particular risk of developing major depression (MD) during PM are those with history of mood sensitivity to female hormone fluctuations i.e., women with a history of premenstrual dysphoric disorder (PMDD) and/or post-partum depression (PPD). Depressive symptomology has been associated with fluctuations of glutamate (Glu) levels in the medial prefrontal cortex (MPFC) in MD patients as well as PMDD and PPD patients. The objective of the study was to compare MPFC Glu levels in healthy perimenopausal and reproductive-aged (RD) women.Methods: Medial prefrontal cortex Glu levels in healthy perimenopausal (n = 15) and healthy RD women (n = 16) were compared via Magnetic Resonance Spectroscopy (MRS) scan using a 3 Tesla (T) magnet. Absence of depressive symptomology and psychiatric comorbidity was confirmed via semi-structured interview. Participants were scanned during the early follicular phase (FP) of the menstrual cycle (MC).Results: Mean MPFC Glu concentrations were decreased in the PM group compared to RD group (PM mean = 0.57 ± 0.03, RD mean = 0.63 ± 0.06, t = −3.84, df = 23.97, p = 0.001).Conclusion: Perimenopause is associated with decreases in MPFC Glu levels. This decrease may be contributing to the increased risk of experiencing depression during PM. Further research should assess MPFC Glu levels in perimenopausal women suffering from MD.

Highlights

The perimenopause (PM) is a phase within the normal female reproductive life cycle marked by the end of menstrual cycle (MC) regularity
Risk factors for PM depression include a history of major depression (MD) or a history of mood sensitivity to female hormone fluctuations [i.e., a history of premenstrual dysphoric disorder (PMDD) or post-partum depression (PPD)] [2, 3]
We found increased medial prefrontal cortex (MPFC) Glu levels in women suffering from PPD [10], suggesting that MPFC Glu levels may play a role in episodes of MD occurring in the context of female hormone fluctuations

Summary

Introduction

The perimenopause (PM) is a phase within the normal female reproductive life cycle marked by the end of menstrual cycle (MC) regularity. Risk factors for PM depression include a history of major depression (MD) or a history of mood sensitivity to female hormone fluctuations [i.e., a history of premenstrual dysphoric disorder (PMDD) or post-partum depression (PPD)] [2, 3]. The peripheral physiological alterations associated with the PM are well-understood, little is known regarding the impact of PM on brain biology. Without such knowledge, it is difficult to investigate the cerebral mechanisms responsible for the increased risk of MD during PM. Glutamate (Glu), the major excitatory neurotransmitter, is widespread throughout the brain functioning at approximately 60% of the synapses within the central nervous system [4]. An increasing body of evidence supports the involvement of the glutamatergic system in the pathophysiology of MD [5]

Methods

Results

Conclusion