Decreased Cerebrospinal Fluid Allopregnanolone Levels in Women with Posttraumatic Stress Disorder

• Published in: Biological psychiatry (1969) 2006-10, Vol.60 (7), p.704-713
• Main Authors: Rasmusson, Ann M., Pinna, Graziano, Paliwal, Prashni, Weisman, David, Gottschalk, Christopher, Charney, Dennis, Krystal, John, Guidotti, Alessandro
• Format: Article
• Language: English
• Subjects: 5-alpha-Dihydroprogesterone - cerebrospinal fluid; Adult; Adult and adolescent clinical studies; Affect; allopregnanolone; Analysis of Variance; Anxiety disorders. Neuroses; Biological and medical sciences; dehydroepiandrosterone; Dehydroepiandrosterone - cerebrospinal fluid; Depression; Female; GABA; Humans; Medical sciences; Menstrual Cycle - cerebrospinal fluid; Mood disorders; Post-traumatic stress disorder; Posttraumatic stress disorder; Pregnanolone - cerebrospinal fluid; Progesterone - cerebrospinal fluid; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptors, GABA-A - metabolism; Reference Values; Stress Disorders, Post-Traumatic - cerebrospinal fluid; Stress Disorders, Post-Traumatic - metabolism; women
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.03.026

Alterations in the γ-amino-butyric acid (GABA) neurotransmitter system have been identified in some populations with posttraumatic stress disorder (PTSD). 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), 5α-dihydroprogesterone (5α-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. There were no group differences in progesterone, 5α-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). 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.