title: CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI.
abstract: Recently several steroid compounds have been discovered to act as neuromodulators in diverse central nervous system (CNS) functions. We wondered if neuroactive steroids might be involved in affective illness or in the mode of action of mood-regulating medications such as carbamazepine. Levels of the neuroactive steroids pregnenolone and progesterone, 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 subjects who were clinically depressed at the time of the LP had lower CSF 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 differences 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 carbamazepine. CSF pregnenolone is decreased in subjects with affective illness, particularly during episodes of active depression. Further research into the role of neuroactive steroids in mood regulation is warranted.
authors.affiliation: Biological Psychiatry Branch, National Institutes of Mental Health, Bethesda, MD 20892.
authors.forename: M S
authors.initials: MS
authors.lastname: George
authors.forename: A
authors.initials: A
authors.lastname: Guidotti
authors.forename: D
authors.initials: D
authors.lastname: Rubinow
authors.forename: B
authors.initials: B
authors.lastname: Pan
authors.forename: K
authors.initials: K
authors.lastname: Mikalauskas
authors.forename: R M
authors.initials: RM
authors.lastname: Post
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000523:psychology; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D002352:Carrier Proteins / Q000134:cerebrospinal fluid* / Q000187:drug effects; D003866:Depressive Disorder / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000523:psychology; D026261:Diazepam Binding Inhibitor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010552:Personality Assessment; D011284:Pregnenolone / Q000134:cerebrospinal fluid*; D011374:Progesterone / Q000134:cerebrospinal fluid*; D012008:Recurrence
chemical_list: D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D002220:Carbamazepine; D011374:Progesterone; D011284:Pregnenolone