The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.

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Corticotropin releasing factor (CRF) may regulate endocrine, autonomic, and behavioral responses to stress. Evidence indicates that CRF-like immunoreactivity (CRF-LI) is widely distributed throughout the CNS. In this study, the distribution of CRF-LI was determined in 36 rat brain regions by combined radioimmunoassay-micropunch dissection techniques and the effect of stress on CRF-LI was investigated, using a chronic stress model that induces endocrine changes in rats similar to those seen in depressed humans. A control group of rats was handled daily. An acute stress group was subjected to 3 hr of immobilization at 4 degrees C, while a chronic stress group was exposed to unpredictable stressors. Thirty-six brain regions were microdissected by the technique of Palkovits and assayed for CRF-LI, using a specific antiserum to ovine CRF. CRF-LI was detected in most regions. In controls, the highest concentrations were found in the arcuate nucleus/median eminence, the hypothalamic paraventricular (PVN) nucleus, and the periventricular nucleus. The next highest levels were found in the raphe nuclei and dorsal vagal complex. CRF-LI was well represented in the locus coeruleus (LC); in the central, cortical, and medial amygdaloid nuclei; and in the bed nucleus of the stria terminalis. Low concentrations occurred in the hippocampus and cerebrocortical regions. Appreciable concentrations were detected in midbrain and brain stem regions. Acute stress reduced CRF-LI in the arcuate nucleus/median eminence (ME) (by 52%) and in the median preoptic (MPO) nucleus (by 32%) and doubled its concentration in the locus coeruleus.(ABSTRACT TRUNCATED AT 250 WORDS)

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