Fig. 3.

Theoretical framework of the multi-system dysregulation caused by stress and the potential restoration of homeostasis by neuroactive steroids. Acute stress causes an increase in neuroactive steroids, CRF, glucocorticoids and proinflammatory neuroimmune signaling. Chronic stress induces a decrease of neuroactive steroids and GABAergic signaling while increasing CRF and TLR4 neuroimmune signaling. Neuroactive steroids may restore homeostasis by increasing GABA_A receptor-mediated inhibition, decreasing CRF, and stabilizing glucocorticoids release and deleterious TLR4 signaling, all of which contribute to the etiology of stress-related psychiatric disorders. (PREG = pregnenolone; ALLO = allopregnanolone; CORT = cortisol/corticosterone). (Created with Biorender.com).