Impaired lymphocyte stimulation by mitogens in severely depressed patients: a complex interface with HPA-axis hyperfunction, noradrenergic activity and ageing process

Article Abstract:

To evaluate interactions of impaired immune competence, noradrenergic activity (actions of substances associated with neural excitation), regulation of cortisol (hormone associated with metabolism and anti-inflammation), age, and depression, 48 male and female patients aged 20 to 75 years who were diagnosed with either major or minor depressive disorder were studied. The patients were free of medical disorders which could alter immune function. Immune competence was studied by testing the response of T-cell lymphocytes to stimulation by three mitogens (substances that induce cell division): pokeweed mitogen (PWM), phytohemagglutinin (PHA) and concanavalin A (Con A). Prior research has linked impaired immune competence with low levels of lymphocyte responses to stimulation by these mitogens. Eight days after hospital admission, the dexamethasone suppression test (DST) was performed to determine the ability of dexamethasone to suppress the production of cortisol (an adrenal hormone); blood lymphocytes were measured and the patients and were given one milligram of dexamethasone (an anti-inflammation steroid). Alterations in the production of cortisol and urine excretion levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), which is the major metabolite of noradrenaline, have also been demonstrated in severe depression. Cortisol assay was performed 24 hours after dexamethasone intake, and urine MHPG output was determined by high-performance liquid chromatography. Data analysis revealed that lymphocyte responses to PHA and PWM were significantly lower in patients with major depression than in those with minor depression. The DST demonstrated that non-suppression was related to low-lymphocyte stimulation by all three mitogens, so that major depressives had significantly higher post-DST cortisol values than patients with minor depression. High MHPG levels were only related to low lymphocyte response to PHA, while increasing age was associated with a general lowered lymphocyte response. (Consumer Summary produced by Reliance Medical Information, Inc.)

Testing, Depression (Mood disorder), Lymphocyte transformation

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The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders: a Nordic multicentre study

Article Abstract:

Research has demonstrated low levels of serotonin (5-HT) in patients with Alzheimer's disease (AD), vascular dementia (VD), and senile dementia of Alzheimer type (SDAT). Citalopram is an antidepressant medication which blocks the reuptake of 5-HT into serotonin receptors, leaving more active serotonin free in the body system. To assess the effects of citalopram in dementia disorders, 98 patients diagnosed with moderate AD, SDAT or VD were evaluated in Norway in a double-blind study of citalopram versus placebo (neither the patients nor the experimenters knew who received citalopram and who received placebo). All patients took placebo for one week (baseline period), and were then randomly assigned to either citalopram or placebo treatment for four weeks. After this, all patients knowingly took citalopram for eight weeks, and then were again randomly assigned to either placebo or citalopram treatment for a few weeks, when withdrawal effects were evaluated. Various scales, physical exams and laboratory tests assessed treatment efficacy and side effects at the end of the baseline period and over the course of the experiment. Baseline ratings indicated emotional disturbances in 85 patients. The most common disturbances were mild depression, low motivation, emotional blunting, anxiety and confusion. After four weeks of double-blind treatment, the AD and SDAT patients treated with citalopram showed significant improvements in emotional blunting, confusion, irritability, anxiety, panic, depressed mood and restlessness. Citalopram was not found to have any significant effects on the VD population, and no effects were found in placebo-treated patients. Citalopram led to very few and very mild side-effects. No withdrawal symptoms were found when administration of citalopram was stopped. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Dementia, Alzheimer's disease, Serotoninergic mechanisms, Anti-Alzheimer's disease agents, Citalopram

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The predictive value of the dexamethasone suppression test: a placebo-controlled study

Article Abstract:

The hypothalamic-pituitary-adrenal (HPA) axis is a complicated network which releases hormones that induce the adrenal cortex to secrete the hormone cortisol, which is important in several metabolic processes. A technique to study HPA activity is the dexamethasone suppression test (DST), which determines the ability of dexamethasone to suppress the HPA axis for 24 hours. A positive test result indicates inadequate cortisol suppression and is a common finding among depressed patients. To evaluate the DST as a predictor of good or poor response to two types of antidepressant treatments, 137 adult patients with major depressive disorder were studied. The patients were placed on a one-week placebo trial after taking the DST. They were then reassessed. The 122 patients who did not significantly improve during the placebo trial entered the second phase of the study. In a double-blind condition (neither patients or experimenters knew which medication patients were receiving), each patient was given either a six-week trial of paroxetine (a serotonin re-uptake inhibitor), or imipramine (a serotonin and norepinephrine re-uptake inhibitor) or continued on placebo. DST results did not predict response to either antidepressant. However, patients with positive DST results did not respond well to placebo, while patients with negative DST results showed significant improvement on placebo. Findings suggest that a positive test may indicate a biological base for depression and the need for active pharmacological treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Usage, Hypothalamic-pituitary-adrenal axis, Pituitary hormone releasing factors, Pituitary hormone releasing hormones

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