Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients.

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.

Alterations in cerebrospinal fluid concentrations of somatostatinlike immunoreactivity in neuropsychiatric disorders.

The concentration of somatostatinlike immunoreactivity in cerebrospinal fluid (CSF) from normal, healthy volunteers (n = 10) and patients with DSM-III diagnoses of major depression (n = 17), schizophrenia (n = 11), or dementia (n = 29) was measured by a sensitive and specific radioimmunoassay. Statistically significant decreases in CSF concentrations of somatostatinlike immunoreactivity were seen in all three patient populations when compared with controls. These findings confirm previous reports of decreased concentrations of somatostatinlike immunoreactivity in the CSF of patients with depression and dementia and extend this observation to patients with schizophrenia as well. These findings are concordant with the view that reductions in somatostatinlike immunoreactivity concentrations are associated with diseases in which cognitive function is disturbed.

Determinations of 5-hydroxyindoleacetic acid and homovanillic acid in human CSF with monitoring of probenecid levels in CSF and plasma.

The accumulation of 5-HIAA and HVA in cerebrospinal fluid (CSF) was studied in eight healthy volunteers after oral administration of probenecid. Simulation indicated that a dose of 4.5 g probenecid should be used to achieve probenecid plasma concentrations between 200 and 400 micrograms/ml. Almost complete inhibition of the active transport of the acidic metabolites was assumed to be obtained at these concentrations. Probenecid 4.5 g was administered in two doses (2.5 g and 2 g), separated by 4 h. Plasma samples were drawn at varying intervals over a period of 46 h and lumbar puncture (LP) was performed at either 14 h or 20 h after the first administration of probenecid. The concentration of probenecid, 5-HIAA and HVA in CSF was estimated and the probenecid-induced accumulation of 5-HIAA and HVA was compared with their baseline values. There were no statistically significant differences (P greater than 0.05) in the accumulation of the monoamine metabolites between the two LP (14 h and 20 h), neither were there any differences in CSF concentrations of probenecid at the time of LP. There were only small differences in probenecid plasma concentrations, although statistically significant. Due to maximum blockade of the active transport system no correlation was observed between the CSF concentration of probenecid and the induced accumulation of 5-HIAA and HVA, respectively. The range of probenecid-induced accumulation for 5-HIAA and HVA in these volunteers was 156-429% and 183-600%, respectively. The suggested monitoring of probenecid plasma levels is proposed as a suitable model to investigate central neuronal activity of dopamine and serotonin in the central nervous system.

Delta-sleep inducing peptide in cerebrospinal fluid from schizophrenics, depressives and healthy volunteers.

CSF levels of DSIP was measured in healthy volunteers and in hospitalized patients with schizophrenia or major depressive disorders. Both patient groups had significantly lower CSF levels of DSIP than the healthy volunteers. There was a tendency for lower CSF levels of DSIP in female compared to male schizophrenics. Neuroleptic treatment did not significantly affect those levels. The levels of DSIP in CSF tended to be inversely correlated to the sleep disturbancy scores in the depressed patients.