LOW CEREBROSPINAL-FLUID CORTICOTROPIN-RELEASING HORMONE CONCENTRATIONS IN EUCORTISOLEMIC DEPRESSION

Hypersecretion of corticotropin-releasing hormone (CRH) and resulting hypercortisolism have been implicated in the pathogenesis of major dep ression, To test this CRH hypersecretion hypothesis, cerebrospinal flu id (CSF) was continuously withdrawn from 11:00 AM to 5:00 PM via an in dwelling subarachnoid catheter (placed at 8:00 AM), and immunoreactive CRH concentrations were determined at 10-min intervals in 10 depresse d patients, the majority of whom exhibited at least one ''atypical'' s ymptom, and in 15 normal volunteers. CSF CRH was low, plasma adrenocor ticotropin (ACTH) fended to be low, and plasma cortisol was normal in the depressed patients. Also, tobacco smokers had lower CSF CRH than n onsmokers. CRH increased acutely in response to lumbar puncture, had a brief half-life, showed rapid variability in concentration over time, and displayed a diurnal concentration rhythm that was preserved in fa sting individuals and in most depressed patients, CSF CRH did not corr elate with plasma ACTH or cortisol; this and its rapidly fluctuating l evels suggest a primarily extrahypothalamic origin of lumbar CSF CRH. (C) 1997 Society of Biological Psychiatry.