Biological Psychiatry
Volume 60, Issue 7 , 1 October 2006, Pages 704-713
doi:10.1016/j.biopsych.2006.03.026
Copyright © 2006 Society of Biological Psychiatry Published by Elsevier Inc.

Original article

Decreased Cerebrospinal Fluid Allopregnanolone Levels in Women with Posttraumatic Stress Disorder

Ann M. Rasmusson a,d,,, Graziano Pinna e, Prashni Paliwal a,c, David Weisman b, Christopher Gottschalk a,b, Dennis Charney f, John Krystal a,dand Alessandro Guidotti e
aDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
bDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut
cDivision of Women's Behavioral Health, Yale University School of Medicine, New Haven, Connecticut
dClinical Neuroscience Division Veterans Affairs National Center for PTSD, West Haven, Connecticut
ePsychiatric Institute, University of Illinois, Chicago, Illinois
fDepartments of Psychiatry, Neuroscience and Pharmacology Mount Sinai School of Medicine, New York, New York.
Received 10 August 2005; revised 3 March 2006; accepted 7 March 2006. Available online 24 August 2006.

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 Areceptor), 5_-dihydroprogesterone (5alpha-DHP: the immediate precursor for allopregnanolone), dehydroepiandrosterone (DHEA: a negative modulator of GABA Areceptor 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).

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.

Key Words: Posttraumatic stress disorder; depression; allopregnanolone; GABA; dehydroepiandrosterone; women


Address reprint requests to Ann M. Rasmusson, MD, VA Connecticut Healthcare System, Psychiatry Service/116A, 950 Campbell Ave., West Haven, CT 06516