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.

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.

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.

HPLC detection of choline and acetylcholine in serum and urine by an immobilized enzyme reactor followed by chemiluminescence detection.

A method using HPLC has been developed for the detection of choline (Ch) and acetylcholine (ACh) using an immobilized enzyme reactor which converts Ch and ACh into hydrogen peroxide and betaïne. The formed H(2)O(2) is quantified by means of a solid-state peroxyoxalate chemiluminescence detector based on an immobilized fluorophore and addition of oxalate from a solid bed. The conditions necessary for chemiluminescence detection are obtained by using a make-up flow of acetonitrile after the enzyme reactor. Precipitation problems due to the poor solubility of salts in the final acetonitrile-water mixture are circumvented by adding a crown ether to the make-up flow. The reproducibility of the method was calculated to be 3.4-3.7% RSD. Detection limits are in the sub-picomole range and a linear range of at least three orders of magnitude is found. Measurements in urine and serum reveal no matrix effects.

Liquid chromatography with electrochemical detection for the determination of choline and acetylcholine in plasma and red blood cells. Failure to detect acetylcholine in blood of humans and mice.

An assay is described for the measurement of choline in plasma and red blood cells using liquid chromatography, an enzyme reactor and electrochemical detection after a simple sample pretreatment. The intra-assay coefficient of variation for choline was 6.2 and 3.8% in plasma and in red blood cells, respectively. Using this method we have re-investigated the presence of acetylcholine in blood constituents. We were not able to demonstrate acetylcholine with a limit of detection of 10 pmol per ml of plasma or per ml of red blood cells.

Lithium treatment in affective disorders: The significance of strongly elevated erythrocyte choline levels.

In manic-depressive patients treated with lithium salts the transport of choline over the erythrocyte membrane is strongly inhibited, resulting in dramatically increased erythrocyte choline levels (for review see ref. 1). Whether or not there is a relationship between this effect and treatment response is not clear. Data on this issue are scarce possibly because the measurement of treatment response in lithium prophylaxis is very difficult and time consuming. Also the effect on erythrocyte choline is specific for lithium and not for manic-depressive illness. We will address here the question of a possible relation between erythrocyte choline and clinical effects of lithium.

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.

CSF choline levels in groups of patients with cranial trauma or extrapyramidal disorders.

Choline levels in lumbar cerebrospinal fluid (CSF) were measured in patients with craniocerebral trauma (N = 67), Parkinson's disease (N = 20), miscellaneous extrapyramidal disorders (N = 28) and Huntington's chorea (N = 5). No differences in CSF choline levels were observed between these diagnostic groups and a group of neurological controls (N = 22). However, CSF choline levels were found to increase with age.

Occupation of dopamine receptors by N-n-propylnorapomorphine or spiperone and acetylcholine levels in the rat striatum.

In an attempt to quantify the interactions between dopaminergic and cholinergic processes, the consequences of complete or partial activation (with N-n-propylnorapomorphine) or blockade (with spiperone) of dopamine receptors for the acetylcholine levels in the rat striatum were studied. The number of specific striatal binding sites (receptors) of spiperone was nearly three times that of N-n-propylnorapomorphine (76 and 26 pmol g-1 wet weight, respectively). The agonist produced a significant increase in the striatal levels of acetylcholine, but there was no simple relationship between receptor binding and these levels. A linear negative correlation was found between the striatal levels of acetylcholine and specific spiperone binding, showing that further receptor blockade induces a decrease in acetylcholine levels, which is independent of the receptors already occupied by the antagonist. The results of this study are evidence that one striatal dopamine receptor regulates the metabolism of at least 400 molecules of acetylcholine.

CSF choline levels in neurologically disturbed children.

Choline levels in cerebrospinal fluid (CSF) were measured in a large group of neurologically disturbed children (n = 114) and in a control group (n = 15). Only 5 children showed CSF choline levels that differed more than 2 standard deviations from the mean of the total investigated group, suggesting that CSF choline levels are extremely stable. Of the 5 children showing extreme values, 3 suffered primarily from psychomotor retardation. Further analysis showed that the CSF choline levels in the medication-free patient group suffering from psychomotor retardation (n = 18) were significantly elevated in comparison with the control group. CSF choline levels of children were found to fit excellently in the regression line showing the increase of CSF choline levels with age as calculated earlier for adults. Therefore, CSF choline levels appear to increase linearly with age during the whole life span. From direct measurements and from measurements in consecutive fractions of lumbar CSF it is concluded that choline levels in intracranial CSF are 2-3 fold as high as those in lumbar CSF.