PTSD is associated with deficits in synthesis of progesterone metabolites such as allopregnanolone and pregnanolone that potently facilitate gamma-amino-butyric acid (GABA) effects at GABAA receptors. These neurosteroids modulate neuronal firing rate, regional brain connectivity, and activation of amygdala-mediated autonomic nervous system, hypothalamic-pituitary-adrenal axis, and behavioral reactions to unconditioned and conditioned threat. They also play critical roles in learning and memory processes such as extinction and extinction retention and inhibit toll-like receptor activation of intracellular pro-inflammatory pathways. Deficient synthesis of these neurosteroids thus may contribute to individually variable PTSD clinical phenotypes encompassing symptom severity, capacity for PTSD recovery, and vulnerability to common PTSD-comorbidities such as major depression, chronic pain, alcohol and nicotine dependence, cardiovascular disease, metabolic syndrome, reproductive disorders, and autoimmune conditions.
Keywords: Allopregnanolone; Depression; GABA; Neurosteroids; PTSD; Pregnanolone.