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), 5alpha-dihydroprogesterone (5alpha-DHP: the immediate precursor for allopregnanolone), dehydroepiandrosterone (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, 5alpha-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).


CONCLUSIONS
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.
Rasmusson
Ann M
AM
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. ann.rasmusson@yale.edu
Pinna
Graziano
G
Paliwal
Prashni
P
Weisman
David
D
Gottschalk
Christopher
C
Charney
Dennis
D
Krystal
John
J
Guidotti
Alessandro
A
D043582:5-alpha-Dihydroprogesterone / Q000134:cerebrospinal fluid; D000328:Adult; D000339:Affect; D000704:Analysis of Variance; D003687:Dehydroepiandrosterone / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000134:cerebrospinal fluid; D011280:Pregnanolone / Q000134:cerebrospinal fluid*; D011374:Progesterone / Q000134:cerebrospinal fluid*; D011963:Receptors, GABA-A / Q000378:metabolism*; D012016:Reference Values; D013313:Stress Disorders, Post-Traumatic / Q000134:cerebrospinal fluid* / Q000378:metabolism
D011963:Receptors, GABA-A; D003687:Dehydroepiandrosterone; D011374:Progesterone; D043582:5-alpha-Dihydroprogesterone; D011280:Pregnanolone