Investigation of the Role of Glutamate and GABA in Perimenopausal Depression

Abstract

In the perimenopausal period, an event marked by end of menstrual cycle regularity, women are at a greater risk of either experiencing a reoccurrence of a major depressive episode (MDE), or presenting with their first MDE. This risk is greater in women with a history of mood vulnerability related to female hormone fluctuations, such as those diagnosed with premenstrual dysphoric disorder or postpartum depression. This suggests a unique biological mechanism behind the pathophysiology of perimenopausal depression. GABA and Glutamate (Glu) are respectively contributing to inhibitory and excitatory transmission in the brain, and it has been suggested that their imbalance could play a role in the pathophysiology of depressive symptomology. Previous studies demonstrated that Glu and GABA are dysregulated in other depressive disorders triggered by fluctuations of female hormones. GABA and Glu are rarely measured simultaneously in depression research, making interpretation of one neurotransmitter’s dysregulation difficult without information regarding the other, considering their antagonistic activity. We used proton magnetic resonance spectroscopy (MRS) to measure Glu and GABA in the medial prefrontal cortex (MPFC) and the left dorsolateral prefrontal cortex (LDLPFC) of 14 healthy perimenopausal women, and 3 perimenopausal women with current MDE. These two brain regions have been shown to be critical in mood symptomatology and influenced by female hormones. Although the results obtained are an exploratory analysis, this research project may lead to a better understanding of the biological dysregulation associated with perimenopausal depression, and contribute to better therapeutic options.