TY - JOUR
T1 - Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence
AU - Adinoff, Bryon
AU - Anton, Ray
AU - Linnoila, Markku
AU - Guidotti, Alessandra
AU - Nemeroff, Charles B.
AU - Bissette, Garth
N1 - Funding Information:
This work was conducted at the Department of Psychiatry, Medical University of South Carolina, and the VA Medical Center, Charleston; Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine; Department of Pharmacology; Duke University Medical Center. This work was supported by the Upjohn Company and NIMH grant MH-42088.
PY - 1996/9
Y1 - 1996/9
N2 - The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing hormone (CRH) elicit anxiety-like symptoms when administered intracerebroventricularly to laboratory animals. Because of the similarities between the symptoms of certain anxiety states and the alcohol withdrawal syndrome, we hypothesized that increased secretion of either of these endogenous neuropeptides may at least in part, be responsible for the symptoms of alcohol withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and again at 3 week's abstinence (Day 21). In addition, plasma concentrations of cortisol were measured to evaluate the relationship between pituitary-adrenal axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI, was significantly higher on Day 1 than on Day 21. Although there was a significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a significant correlation between CSF CRH and plasma cortisol concentrations was not observed at either time point. Neither CSF neutropeptide correlated with clinical measures of withdrawal severity. These tentative findings may implicate CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the central release of CRH and DBI may not be adequately reflected in lumbar CSF.
AB - The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing hormone (CRH) elicit anxiety-like symptoms when administered intracerebroventricularly to laboratory animals. Because of the similarities between the symptoms of certain anxiety states and the alcohol withdrawal syndrome, we hypothesized that increased secretion of either of these endogenous neuropeptides may at least in part, be responsible for the symptoms of alcohol withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and again at 3 week's abstinence (Day 21). In addition, plasma concentrations of cortisol were measured to evaluate the relationship between pituitary-adrenal axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI, was significantly higher on Day 1 than on Day 21. Although there was a significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a significant correlation between CSF CRH and plasma cortisol concentrations was not observed at either time point. Neither CSF neutropeptide correlated with clinical measures of withdrawal severity. These tentative findings may implicate CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the central release of CRH and DBI may not be adequately reflected in lumbar CSF.
KW - Alcohol withdrawal
KW - Alcoholism
KW - Corticotropin releasing hormone
KW - Diazepam binding inhibitor
KW - GABA receptor
KW - HPA axis
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U2 - 10.1016/0893-133X(95)00212-V
DO - 10.1016/0893-133X(95)00212-V
M3 - Article
C2 - 8873112
AN - SCOPUS:0030249351
SN - 0893-133X
VL - 15
SP - 288
EP - 295
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 3
ER -