Frans Flentge

Urinary free cortisol excretion in elderly persons with minor and major depression

Several studies have found that cortisol hypersecretion may occur in severely depressed patients, characterized by melancholic features. On the other hand, illness chronicity seems to be related to low, rather than high, cortisol levels. This study aims to trace factors associated with 24-h urinary free cortisol levels in a sample of 23 elderly persons with major or minor depression and 21 non-depressed control subjects. Depressive episodes were subdivided according to severity and chronicity (i.e. length and recurrence). None of the depressed persons showed unusually high 24-h cortisol levels, and cortisol excretion was not elevated as compared with that in the control group, regardless of subtype of depression. The results suggest, however, that hyposecretion of cortisol may be a feature of chronic depressive episodes, especially in males.

AN ENZYME-REACTOR FOR ELECTROCHEMICAL MONITORING OF CHOLINE AND ACETYLCHOLINE - APPLICATIONS IN HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY, BRAIN-TISSUE, MICRODIALYSIS AND CEREBROSPINAL-FLUID

A sandwich-type enzyme reactor in which the enzymes are physically immobilized in a minimal dead space between two cellulose membranes, resulting in improved sensitivity, was developed for the electro-chemical detection of choline (Ch) and acetylcholine (ACh). The reactor contains the enzymes choline oxidase with or without acetylcholine esterase, for the detection of ACh and Ch, respectively. For the HPLC analysis of Ch and ACh the detection system was coupled post column. Levels of Ch and ACh of rat striatum tissue and human cerebrospinal fluid were found to be similar to those determined with published methods. Because of low back pressure--a further advantage of the reactor--the detection system could also be directly coupled to the outlet of a microdialysis device, allowing the on-line real-time measurement of extracellular brain Ch. The versatility of the enzyme reactor for the monitoring of analytes in HPLC eluates, flow injection analysis, with or without prepurification, is emphasized. The usefulness of the reactor-detector system in biomedical applications is illustrated by the measurement of increases of rat striatal extracellular Ch following cardiac arrest.

Potential psychosocial mechanisms linking depression to immune function in elderly subjects

Although depression and immune changes in elderly subjects constitute a considerable health risk, mechanisms underlying the association between depression and immune function are unclear. The question of whether personality and social support can explain the variation in immune function during depression was addressed in 21 elderly depressive and 23 control subjects. The following variables were studied: neuroticism, extraversion, received social support, depression-related immune parameters [i.e. numbers of lymphocytes, lymphocyte subsets CD3+, CD8+, natural killer-like T cells (NKT), CD4/CD8 ratio, and interleukin-6 (Il-6)]. We found that neuroticism reduced the association between depression and Il-6 (from 62 to 22.4%) and between depression and CD3+ (from 27.6 to 21.6%), and was also directly related to Il-6 (i.e. adjusted for age and depression). Social support reduced the association between depression and NKT cells from 25 to 18%, while it was also directly related to NKT cells. Extraversion, adjusted for age and depression, was negatively related to CD4/CD8 ratio. Subjects with high extraversion and high social support had more NKT cells. We concluded that changes in immune function during depression can partly be explained by neuroticism and received social support, whereas immune function is also directly related to these psychosocial variables. Neuroticism may exert its contribution to the risk for depression partly via Il-6 production.

Effects of total sleep deprivation on urinary cortisol, self-rated arousal, and mood in depressed patients

The possibility that the clinical response to total sleep deprivation (TSD) is mediated by dimensions of arousal was investigated in a group of 16 depressed patients. Self-reports of activation, stress, and mood were assessed 3 days before, during, and 2 days after TSD. Urinary cortisol excretion and responses to the dexamethasone suppression test (DST) were also measured. TSD increased cortisol excretion in depressed patients and advanced the time of the maximal excretion of cortisol. No such changes have been reported for normal subjects. Neither the increased excretion nor the time shift was related to the mood response to TSD. The DST results were also unrelated to this response. Indications that the mood response to TSD may be mediated by dimensions of arousal are the significant relationships between this response and the responses of subjective stress and activation to TSD. The TSD-induced cortisol increase was not related to the subjective arousal response to TSD. The increased cortisol excretion itself could be predicted by the averaged baseline levels of subjective stress: the lower the stress levels before TSD, the larger the cortisol response to TSD.

The influence of probenecid on the metabolism of serotonin, dopamine and their precursors in man

Probenecid inhibits the efflux of acid monoamine (MA) metabolites from the CNS. The probenecid-induced accumulation of these metabolites in the CSF in man supplies data on the central turnover of the corresponding amines. In this study an attempt was made to establish whether probenecid also exerts an influence on the metabolism of the MA precursors: tryptophan and tyrosine. The principal conclusions were the following.1.Whereas in rats probenecid lowers the serum tryptophan level and elevates that in the brain (probably as a result of interference with the binding of tryptophan to serum albumins), the serum tryptophan level in human individuals is also lowered but the CSF concentration remains unchanged. After an oral tryptophan load, however, the CSF tryptophan concentration does increase.It is suggested that in man, endogenously released and exogenous tryptophan enter different metabolic pools in the brain.2.After an oral load of 1-tryptophan, for the most part depressive patients showed a more rapid increase in CSF tryptophan concentration and a less marked rise of the CSF 5-HIAA level than did the psychologically undisturbed test subjects examined by Eccleston et al. It seems possible that, in the depressive patient, the tryptophan-metabolizing capacity is disturbed.3.After an oral load of 1-tryptophan the CSF HVA concentration increased. Possibly, tryptophan is transformed to 5-HT in dopaminergic neurons, and this 5-HT may supersede the DA from the storage sites. This effect may well be of significance in the therapeutic application of 5-HT precursors.4.The CSF concentrations of 5-HIAA, HVA, tryptophan and tyrosine show no systematic variations during the day.

The origin of CSF choline and its relation to acetylcholine metabolism in brain

Abstract Elevation of serum choline levels in the rabbit either by intravenous injection of choline or by the pharmacological action of oxotremorine results in a rise in cisternal CSF choline levels. It was excluded that the oxotremorine induced rise in CSF choline levels can be ascribed to its action on the CNS. Therefore changes in CSF choline levels can be merely the result of changes in peripheral choline stores and do not necessarily reflect changes in the cholinergic activity of the CNS. From isotopic labelling experiments the contribution of serum choline to CSF choline was found to be 42%.

Increase of NK–T cells in aged depressed patients not treated with antidepressive drugs

BACKGROUND A change in number and/or activity of natural killer cells has repeatedly been reported in depressive illness. Much less attention has yet been given to the subgroup of natural killer cells that are positive for the T-cell marker CD3 (NK-T cells). These cells possibly have important immunoregulatory properties. METHODS We compared number and percentage of NK-T cells (defined as CD3(+) and CD16(+) and/or CD56(+) by two-color flow cytometry) in the peripheral blood of control subjects and two groups of elderly depressive subjects using or not using antidepressive drugs. RESULTS The number and percentage of NK-T cells were strongly elevated in elderly depressive subjects not using antidepressive drugs, as compared with control subjects and elderly depressive subjects using antidepressive drugs. CONCLUSIONS Depressive illness in a geriatric population is associated with a substantial increase of NK-T cells. This increase was absent in a depressive group using antidepressive drugs.

Automated assay of tryptophan at the nanogram level: Determination of tryptophan in cerebrospinal fluid and of total and nonprotein bound tryptophan in serum

Abstract An automated fluorometric assay of tryptophan in serum and cerebrospinal fluid is described. In addition a comparison between two existing methods to isolate free tryptophan from serum was made. The method in which serum is centrifuged through Diaflo CF 50 membrane cones was shown to be unreliable, while the method in which serum is centrifuged through dialysis bags produced satisfactory results. The latter method was adapted for the isolation of free tryptophan from small volumes of serum.

On-line real-time monitoring of extracellular lactate, ethanol, glucose and choline, using microdialysis and enzyme reactors

Publisher Summary This chapter discusses experimental results of on-line real-time monitoring of extracellular lactate, glucose, ethanol, and choline using microdialysis and enzyme reactors. A continuous signal representing the extracellular concentrations of lactate may directly be correlated to function or behavior. This technique, designated as lactography, to emphasize its on-line nearly real-time nature has been developed by Kuhr and Korf. The lactate concentration in the dialysate is only a fraction of the extracellular lactate concentration because the diffusion to the dialysate never reaches equilibrium, and thus, a concentration gradient is maintained to drive the lactate into the perfusate. At high-perfusion rates, there is an inverse relationship between flow rate and concentration of lactate in the dialysate, and at low-flow rates, concentrations in the dialysate and the extracellular fluid approach each other. The assay for the continuous detection of choline is used to show an increase in the striatal extracellular concentrations after cardiac arrest. Lactate is formed under both normoxic and hypoxic conditions. Lactate production in resting normoxic muscle is very slow.

RS-86 IN MANIC DISORDER

Recently, the spiropiperidyl derivate RS 86, a specific muscarinic agonist, attracted attention in the context of the cholinergic hypothesis of Alzheimers disease. This compound revived the interest in the clinical usefulness of cholinergic agents in mania. In the present report, the findings in eight patients subjected to the same design will be summarized