CSF NEUROACTIVE STEROIDS IN AFFECTIVE-DISORDERS - PREGNENOLONE, PROGESTERONE, AND DBI

Recently several steroid compounds have been discovered to act as neur omodulators in diverse central nervous system (CNS) functions. We wond ered if neuroactive steroids might be involved in affective illness or in the mode of action of mood-regulating medications such as carbamaz epine. Levels of the neuroactive steroids pregnenolone and progesteron e, as well as the neuropeptide diazepam binding inhibitor (DBI) (known to promote steroidogenesis), were analyzed from cerebrospinal fluid ( CSF) obtained by lumbar puncture (LP) from 27 medication-free subjects with affective illness and 10 healthy volunteers. Mood-disordered sub jects who were clinically depressed at the time of the LP had lower CS F pregnenolone (n = 9, 0.16 ng/ml) compared with euthymic volunteers ( n = 10, 0.35 ng/ml; p < 0.01). In addition, pregnenolone was lower in all affectively ill subjects (n = 26, 0.21 ng/ml), regardless of mood state on the LP day, than healthy volunteers (p < 0.05). No difference s were found for progesterone or DBI levels by mood state or diagnosis . Progesterone, pregnenolone, and DBI did not change significantly or consistently in affectively ill subjects after treatment with carbamaz epine. CSF pregnenolone is decreased in subjects with affective illnes s, particularly during episodes of active depression. Further research into the role of neuroactive steroids in mood regulation is warranted .