Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?
Shannon K. Crowley; Susan S. Girdler
Psychopharmacology2014
Summary (paraphrased)
Focused on human data, this review surveys how neurosteroids, GABAergic signaling, and the HPA axis regulate each other: allopregnanolone and allo-THDOC act as an allostatic brake that terminates stress-induced HPA activation, and chronic stress degrades this brake. The authors link disrupted neurosteroid–GABA–HPA coupling to vulnerability for depression and stress-related disorders in people, and review what is known about neurosteroid measurements in human plasma, CSF, and brain. It is the human-translation counterpart to the rodent THDOC literature.
Why it’s in the systems review
The human-focused counterpart to the rodent THDOC literature: it documents that allopregnanolone/allo-THDOC normally brake the HPA axis and that chronic stress degrades this brake — the feedback-loop architecture Powers' model invokes. For a corpus built partly on patient-reported phenotypes, having the human regulatory physiology in the record matters more than another rodent study. It ties neurosteroid dysregulation to the exact mood-disorder outcomes the corpus tracks.
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