Serial Cerebrospinal Fluid Corticotropin-releasing Hormone Concentrations in Healthy and Depressed Humans

CRH, a hypothalamic peptide that is the most potent ACTH secretagogue known, also appears to be produced in the cerebral cortex and spinal cord. Depressed patients have blunted responses to exogenous CRH and normal to high concentrations of CRH immunoreactivity in single morning samples of lumbar cerebrospinal fluid (CSF). Although these data suggest that depression may be associated with hypersecretion of CRH, it has also been postulated that central nervous system insufficiency of CRH might have a pathophysiological role in certain depressive syndromes. We continuously sampled lumbar CSF via indwelling subarachnoid catheters from 1100-1700 h and measured CRH at 10-min intervals in depressed patients and normal subjects. A standardized mixed liquid meal was administered at 1300 h. CSF CRH was strikingly reduced in depressed patients compared to normal subjects [4.2 +/- 1.1 pmol/L vs. 13 +/- 2.1 pmol/L (mean +/- SEM), respectively, P less than 0.01 by Wilcoxon test]. CSF CRH concentrations rose progressively during the experiment in both groups, suggesting a diurnal rhythm and, possibly, response to a test meal. CRH had a very brief half-life in CSF (less than 10 min), suggesting that the spinal cord is the origin of CRH in lumbar CSF. The rapid transients in CSF CRH concentration demonstrate that single samples provide very limited information. There were no intraindividual correlations between CSF CRH concentrations and those of either plasma ACTH or cortisol, both of which rose in response to eating. The present data show that impaired central nervous system secretion of CRH can exist during states of severe depression.