Differential modulation of cytokine production in major depressive disorder by cortisol and dexamethasone.

In major depressive disorder (MDD), there is increasing evidence of a relationship between neuroendocrine and immunological alterations. Therefore, we investigated the influence of cortisol and dexamethasone on the in vitro production of TNF-alpha and IL-6 in blood cells of depressed inpatients at admission, in the course of MDD and in healthy controls. Patients were psychopathologically classified as responders and non-responders after a 6-week antidepressant treatment. At admission in the responder subgroup, incubation with both steroids under basal conditions resulted in an increase of TNF-alpha levels, which decreased after treatment. After stimulation with phytohemagglutinin, an enhancement of TNF-alpha suppression by steroids was detectable after successful antidepressive treatment. A significant relationship was seen between the cortisol-induced modulation of TNF-alpha levels and the psychopathology in this subgroup. Under basal conditions, IL-6 levels were increased after treatment with both steroids. The data suggest a normalization of the altered effects of glucocorticoids on TNF-alpha production in the responder subgroup only.

Cytokine production and treatment response in major depressive disorder.

In a controlled study, such immunological parameters as whole blood production of the cytokines interleukin-6 (IL-6) and tumor-necrosis factor-alpha (TNF-alpha) were assessed in 24 inpatients with a major depressive disorder (MDD) both before and again under treatment. After a 6-week treatment period with amitriptyline, patients were classified as responders or nonresponders according to their psychopathological outcome as evaluated by the Hamilton and the Montgomery-Asberg Depression Rating Scales. Pre-treatment levels of c-reactive protein (CRP) were significantly higher in both patient subgroups than in the control subjects. In comparison to the controls, unstimulated pretreatment production of IL-6 was significantly decreased in the responders; whereas it was significantly increased in the nonresponder subgroup. Post-treatment values did not differ significantly among the patient and control groups. Pretreatment levels of TNF-alpha were increased in both patient subgroups, with a significant decrease during treatment only in the responder subgroup. Pretreatment levels of IL-6/10(5) mononuclear cells and the ratio between lymphocytes and monocytes acted as independent variables with regard to the clinical response. Our data indicate that unstimulated secretion of TNF-alpha is related to the psychopathological improvement; whereas, IL-6 levels might dichotomize the patients into subsequent responders and nonresponders already at admission.

Regulation of glucocorticoid receptor-mRNA in human blood cells by amitriptyline and dexamethasone.

Recent research suggests that antidepressants exert their clinical action in depression via the restoration of glucocorticoid receptor (GR) function with a subsequent normalization of the altered feed-back regulation of the hypothalamic-pituitary adrenocortical (HPA) system. We, therefore, studied the effects of amitriptyline, a standard antidepressant, and of the glucocorticoid dexamethasone, which has recently been reported to possess antidepressive properties, on glucocorticoid receptor mRNA (GR-mRNA) derived from blood cells of healthy male volunteers. Whole blood samples were exposed in vitro for 24 h to amitriptyline and dexamethasone, the mRNA was extracted, transcripts of the 'house-keeping gene' glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the GR-gene were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) and semiquantitatively determined by subsequent densitometry. In a concentration of 10 nM, amitriptyline induced a significant increase in GR-mRNA (GR/GAPDH ratio) to 186 +/- 31% of the control condition, while a concentration of 10 microM of amitriptyline resulted in an increase of GR-mRNA (GR/GAPDH ratio) to 165 +/- 36%. Dexamethasone also up-regulated blood cell GR-mRNA (GR/GAPDH ratio) levels at a concentration of 10 nM to 184 +/- 29%, whereas an incubation with 10 microM apparently resulted in toxic effects on blood cells with a decreased amount of total mRNA samples recovered. In conclusion, we here show an increase of GR-mRNA in human blood cells after treatment with amitriptyline and dexamethasone, pointing to a direct action of these substances on GR-gene expression in a human system.

Impairment of facial recognition in patients with right cerebral infarcts quantified by computer aided "morphing".

OBJECTIVE: To investigate where facial recognition is located anatomically and to establish whether there is a graded transition from unimpaired recognition of faces to complete prosopagnosia after infarctions in the territory of the middle cerebral artery. METHODS: A computerised morphing program was developed which shows 30 frames gradually changing from portrait photographs of unfamiliar persons to those of well known persons. With a standardised protocol, 31 patients with right and left sided infarctions in the territory of the middle cerebral artery and an age and sex matched control group were compared by non-parametric tests. RESULTS AND CONCLUSION: Facial recognition in patients with right sided lesions was significantly impaired compared with controls and with patients with left sided lesions. A graded impairment in facial recognition in patients with right sided ischaemic infarcts in the territory of the middle cerebral artery seems to exist.