Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder

Background. Alterations in the gamma-amino-butyric acid (GABA) neurotransmitter system have been identified in some populations with posttraumatic stress disorder (PTSD). Methods: To further investigate factors of relevance to GABAergic neurotransmission in PTSD, we measured cerebrospinal fluid (CSF) levels of allopregnanolone and pregnanolone combined (ALLO: congeners that potently and positively modulate effects of GABA at the GABA(A) receptor), 5 alpha-dihydroprogesterone (5 alpha-DHP: the immediate precursor for allopregnanolone), dehydroepi-androsterone (DHEA: a negative modulator of GABA(A) receptor function), and progesterone with gas chromatography, mass spectrometry in premenopausal women with (n = 9) and without (n = 10) PTSD. Subjects were free of psychotropic medications, alcohol, and illicit drugs; all were in the follicular phase of the menstrual cycle except three healthy and four PTSD subjects receiving oral contraceptives. Results: There were no group differences in progesterone, 5 alpha-DHP, or DHEA levels. The PTSD group ALLO levels were < 39% of healthy group levels. The ALLO/DHEA ratio correlated negatively with PTSD re-experiencing symptoms (n = -82, p < 008; trend) and with Profile of Mood State depression/dejection scores (n = -0.70, p < 0008). Conclusion: Low CSF ALLO levels in premenopausal women with PTSD might contribute to an imbalance in inhibitory versus excitatory neurotransmission, resulting in increased PTSD re-experiencing and depressive symptoms.