Allopregnanolone and mood disorders

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Please post here studies related to Allopregnanolone and mood disorders.

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Keywords: Allopregnanolone Mood GABA Anxiety Depression Alcohol Benzodiazepine Amygdala

ncbi.nlm.nih.gov/pubmed/23978486

Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties.

Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone.

ncbi.nlm.nih.gov/pubmed/24215796

During the last years, the downregulation of neurosteroid biosynthesis has been intensively discussed to be a possible contributor to the development of anxiety and depressive disorder.

The importance of allopregnanolone for the regulation of emotion and its therapeutical use in depression and anxiety may not only involve GABAergic mechanisms, but probably also includes enhancement of neurogenesis, myelination, neuroprotection, and regulatory effects on HPA axis function.

ncbi.nlm.nih.gov/pubmed/23348009

These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion. Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology.