Cerebrospinal fluid immunoreactive somatostatin concentrations in patients with Cushing's disease and major depression: relationship to indices of corticotropin-releasing hormone and cortisol secretion.
To further explore the differential effects of peripherally and centrally derived hypercortisolism on neurohormonal systems implicated in the pathophysiology of mood and cognitive disturbances, we examined the cerebrospinal fluid (CSF) concentrations of immunoreactive somatostatin (IR-SRIF) in patients with Cushing's disease and major depression and the relationship of these levels to CSF immunoreactive corticotropin-releasing hormone (CRH) concentrations and urinary free cortisol excretion. In particular, since CSF SRIF levels consistently have been shown to be reduced in depression, we wished to assess whether decreased centrally directed SRIF was more likely a primary or a secondary factor in the hypercortisolism of major depression. CSF SRIF levels were significantly reduced in 11 patients with documented Cushing's disease and in 1 patient with ectopic adrenocorticotropic hormone secretion as compared with both 41 healthy volunteers (19.4 +/- 2.9 vs. 37.4 +/- 1.5 pmol/l; p < 0.01) and 28 patients with major depression (30.2 +/- 2.4 pmol/l; p < 0.05), whose CSF SRIF levels were also significantly reduced as compared with controls (p < 0.05). CSF SRIF levels in the Cushing's disease patients correlated positively with CSF CRH (r = 0.64; p < 0.025), suggesting that either the sustained hypercortisolism in these patients and/or its suppression of central CRH secretion contributed to the reduction in SRIF. A more modest but significant correlation between CSF SRIF and CSF CRH was observed in the healthy volunteers (r = 0.37; d.f. = 37; p < 0.02); in the depressed patients, no linear relationship, but rather an inverted U-shaped relationship was found which significantly fit by a quadratic function (r2 = 0.90; d.f. = 22; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Kling
M A
MA
Clinical Neuroendocrinology Branch, National Institue of Mental Health, Bethesda, Md.
Rubinow
D R
DR
Doran
A R
AR
Roy
A
A
Davis
C L
CL
Calabrese
J R
JR
Nieman
L K
LK
Post
R M
RM
Chrousos
G P
GP
Gold
P W
PW
D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003480:Cushing Syndrome / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D003866:Depressive Disorder / Q000134:cerebrospinal fluid* / Q000209:etiology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011863:Radioimmunoassay; D013004:Somatostatin / Q000134:cerebrospinal fluid*
D013004:Somatostatin; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone