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The role of GABA in PMDD?

Research suggests that changes in gamma-aminobutyric acid (GABA) receptor sensitivity and activity may play a role in Premenstrual Dysphoric Disorder (PMDD). GABA is a neurotransmitter that has inhibitory effects on brain activity, helping to regulate mood and anxiety. Alterations in GABAergic signalling, particularly changes in GABA receptor function, have been proposed as potential contributors to the mood and emotional symptoms associated with PMDD.

doctors looking at MRI images of the brain
PMDD brain changes

Here's how GABA receptor changes may be linked to PMDD:

  1. GABAergic System and Mood Regulation: GABA receptors are critical components of the GABAergic system, which is responsible for modulating neural activity and maintaining a balance between excitation and inhibition in the brain. GABA receptors have inhibitory effects on neurons, helping to reduce neuronal firing and promote a sense of calm and relaxation.

  2. GABA Receptor Subtypes: GABA receptors come in different subtypes, including GABA-A receptors and GABA-B receptors. GABA-A receptors are ionotropic receptors that mediate fast inhibitory neurotransmission, while GABA-B receptors are metabotropic receptors that play a role in slower and more sustained inhibitory signalling.

  3. Allopregnanolone and GABA-A Receptors: Allopregnanolone, a neurosteroid derived from progesterone, enhances the activity of GABA-A receptors. During the luteal phase of the menstrual cycle (the phase before menstruation), when PMDD symptoms are most severe, there is an increase in allopregnanolone levels due to rising progesterone. This increase in allopregnanolone may lead to increased GABA-A receptor activation and heightened inhibitory effects, contributing to mood stabilization.

  4. GABA Receptor Sensitivity Changes: Some research suggests that individuals with PMDD might experience changes in GABA receptor sensitivity and function. It's proposed that these changes in receptor sensitivity could contribute to the mood-related symptoms seen in PMDD, such as irritability, mood swings, and anxiety.

  5. Interplay with Hormonal Fluctuations: Hormonal fluctuations, especially those involving progesterone and allopregnanolone, can impact GABA receptor function. The cyclical changes in these hormones during the menstrual cycle might lead to variations in GABA receptor activity, potentially contributing to the mood disturbances in PMDD.

It's important to note that while these theories are promising, the exact relationship between GABA receptor changes and PMDD is still being studied, and further research is needed to fully understand the complex mechanisms underlying the disorder. Additionally, PMDD is likely influenced by a combination of factors, including genetic predisposition, hormonal fluctuations, neurotransmitter activity, and more.

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