Changes in neuroactive steroid secretion associated with CO2-induced panic attacks in normal individuals

Neuroactive steroids modulate anxiety in experimental animals and possibly in humans. The secretion of these compounds has been found to be altered in panic disorder (PD), with such alterations having been suggested to be a possible cause or effect of panic symptomatology. Panic-like attacks can be induced in healthy individuals by administration of panicogenic agents or by physical procedures, and we have now measured the plasma concen- trations of neuroactive steroids in such individuals before, during, and after panicogenic inhala- tion of CO 2 in order to investigate whether abnormalities of neuroactive steroid secretion might contribute to the pathogenesis of PD. Fifty-nine psychologically and physically healthy subjects, including 42 women (11 in the follicular phase of the menstrual cycle, 14 in the luteal phase, and 17 taking contraceptive pills) and 17 men, who experienced a panic-like attack on previous exposure to 7% CO 2 were again administered 7% CO 2 for 20 min. Thirty-three of these individuals (responders) again experienced a panic-like attack, whereas the remaining 26 subjects did not (nonresponders). All subjects were examined with the VAS-A and PSL-III-R scales for anxiety and panic symptomatology before and after CO 2 inhalation. The plasma concentrations of progester- one, 3a,5a-tetrahydroprogesterone (3a,5a-THPROG = allopregnanolone), 3a,5a-tetrahydrode- soxycorticosterone (3a,5a-THDOC), dehydroepiandrosterone (DHEA), and cortisol were measured 15 min and immediately before the onset of CO2 administration as well as immediately, 10, 30, and 50 min after the end of CO 2 inhalation.