concanavalin-a and Depressive-Disorder

Depression is a serious psychiatric disorder affecting not only the monaminergic, glutamatergic, and GABAergic neurosystems, but also the immune system. Patients suffering from depression show disturbance in the immune parameters as well as increased susceptibility to infections. Zinc is well known as an anti-inflammatory agent, and its link with depression has been proved, zinc deficiency causing depression- and anxiety-like behavior with immune malfunction. It has been discovered that trace-element zinc acts as a neurotransmitter in the central nervous system via zinc receptor GPR39. In this study we investigated whether GPR39 knockout would cause depressive-like behavior as measured by the forced swim test, and whether these changes would coexist with immune malfunction. In GPR39 knockout mice versus a wild-type control we found: i) depressive-like behavior; ii) significantly reduced thymus weight; (iii) reduced cell viability of splenocytes; iv) reduced proliferative response of splenocytes; and v) increased IL-6 production of splenocytes after ConA stimulation and decreased IL-1b and IL-6 release after LPS stimulation. The results indicate depressive-like behavior in GPR39 KO animals with an immune response similar to that observed in depressive disorder. Here for the first time we show immunological changes under GPR39-deficient conditions.

Topics: Animals; Cell Proliferation; Cell Survival; Concanavalin A; Cytokines; Depressive Disorder; Disease Models, Animal; Female; Gene Expression Regulation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogens; Motor Activity; Organ Size; Oxazines; Receptors, G-Protein-Coupled; Spleen; Swimming; Thymocytes; Xanthenes

The biological basis of treatment resistance in depression still remains unclear. Some studies suggest that there exists a relationship between a disturbance in the immune system and depression.. To investigate the immune status of patients with treatment resistant depression, we compared the in-vitro lymphocytic responses to three different mitogens in 10 drug-free patients with treatment resistant depression and 10 normal controls matched for age and sex.. We observed a marked increase in the lymphocyte mitogenic activity to mitogens of T lymphocytes.. This activation of lymphocyte function may be indicative of a pathological stimulation in cell-mediated immunity in patients with treatment resistant depression.

Topics: Adult; Concanavalin A; Depression; Depressive Disorder; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Mitogens; Phytohemagglutinins; Reference Values; T-Lymphocytes

Recently, analysis of partial variance (APV) was proposed as a technique to control for day-to-day variance in mitogen-induced lymphoproliferative responses whereby data obtained from controls, run in the laboratory on the same day, are used as covariates in regression analysis. In order to check the utility of the APV method in the interpretation of functional immune tests, we have reanalyzed lymphoproliferative responses in experimental subjects with depression (n = 38) stimulated by phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (Con A) in relation to responses obtained in laboratory controls. There were no significant relationships between the depressed patients' and laboratory controls' lymphoproliferative responses to PHA, PWM or Con A. Controlling for day-to-day variation by means of regression analysis did not significantly alter the significant relationships between the patients' lymphoproliferative responses and clinical variables, such as depressive classification and severity of illness. It is argued that the APV method may not be used to adjust for an inappropriately high day-to-day variability in immune assays.

Topics: Adult; Analysis of Variance; Case-Control Studies; Chi-Square Distribution; Concanavalin A; Cross-Sectional Studies; Depressive Disorder; Female; Humans; Immunologic Tests; In Vitro Techniques; Lymphocyte Activation; Male; Middle Aged; Mitogens; Phytohemagglutinins; Pokeweed Mitogens; Regression Analysis; Reproducibility of Results; Severity of Illness Index

The effect of in vivo (1 mg) and in vitro (10(-7)-10(-10) M) dexamethasone administration on mitogen-induced lymphocyte proliferation was examined in drug-free depressed patients, nondepressed psychiatric patients, as well as normal controls, and was related to the results of a standard overnight Dexamethasone Suppression Test (DST). The effect of oral dexamethasone administration was also examined for its effect on lymphocyte cytosolic glucocorticoid receptor content. Oral dexamethasone administration significantly decreased both phytohemagglutinin (PHA) and concanavalin A (Con-A) induced lymphocyte proliferation, as well as glucocorticoid receptor number in suppressors, whereas dexamethasone failed to decrease these responses in nonsuppressors. Nonsuppressors had significantly lower serum dexamethasone levels compared to suppressors at both 8:00 AM and 4:00 PM. However, when differences in serum dexamethasone levels were covaried out, there were still significant differences between suppressors and nonsuppressors on the dexamethasone-induced mitogen changes, but the changes in glucocorticoid receptor content were no longer significant. In vitro incubation of lymphocytes with dexamethasone produced a dose-related decrease in mitogenesis, which was not different between the depressed and nondepressed groups. However, at physiologically relevant concentrations of dexamethasone (10(-9)-10(-10) M), nonsuppressors as compared to suppressors were more resistant to the immunosuppressive effects of in vitro dexamethasone on the Con-A response. The inhibitory effect of in vitro dexamethasone on Con-A-stimulated lymphocytes was positively correlated with basal 4:00 PM cortisol values. In conclusion, in vitro techniques are useful probes to assess glucocorticoid sensitivity in depression. The present results also further support the hypothesis that glucocorticoid insensitivity is associated with DST nonsuppression.

Topics: Adult; Cells, Cultured; Circadian Rhythm; Concanavalin A; Depressive Disorder; Dexamethasone; Humans; Hydrocortisone; Lymphocyte Activation; Phytohemagglutinins; Receptors, Glucocorticoid; T-Lymphocytes

Plasma prostaglandin E1 and E2, and quantitative and qualitative measures of immune function, were determined in depressed patients and healthy controls. Prostaglandin E2 was significantly elevated in the depressed group, and prostaglandin E1 showed a trend in the same direction. Lymphocyte stimulation responses, as measured by phytohemagglutinin, concanavalin A, and pokeweed mitogen, were significantly lower in the depressed group. Helper and suppressor T cell percentages did not significantly differ in the two populations. In the depressed group, prostaglandin E1 showed a significant inverse correlation with concanavalin A, and prostaglandin E2 showed a similar trend. These preliminary data suggest prostaglandins of the E series may be related to abnormalities of cellular immunity previously documented in depression.

Topics: Alprostadil; Concanavalin A; Depressive Disorder; Dinoprostone; Female; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Middle Aged; Prostaglandins E; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Approximately 50% of depressed patients are resistant to the cortisol-suppressing effect of dexamethasone. To determine if glucocorticoid resistance could be a more generalized phenomenon in depressed patients, mitogen stimulation tests were performed on lymphocytes from 12 depressed patients and 12 control subjects before and after dexamethasone administration. Suppression of serum cortisol following administration of 1 mg of dexamethasone in four depressed patients and 11 control subjects was associated with a decreased lymphoproliferative response, but no such change occurred in the eight depressed patients and the single control subject who did not suppress cortisol. The dexamethasone-induced changes in the mitogen responses were positively correlated with the highest postdexamethasone serum cortisol values.

Topics: Adult; Concanavalin A; Depressive Disorder; Dexamethasone; Dose-Response Relationship, Immunologic; Female; Humans; Hydrocortisone; Lymphocyte Activation; Male; Phytohemagglutinins; Receptors, Glucocorticoid; T-Lymphocytes

Lymphocyte stimulation by phytohemagglutinin, concanavalin A, and pokeweed mitogen was significantly lower in a group of hospitalized depressed patients than in matched controls. The absolute number of T and B cells was lower in the depressed group, but the percentage of these cell types did not differ between the groups. These findings may be related to the altered neuroendocrine function found in patients with depressive disorders.

Topics: Adult; Aged; B-Lymphocytes; Concanavalin A; Depressive Disorder; Female; Hospitalization; Humans; Hydrocortisone; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Psychiatric Status Rating Scales; T-Lymphocytes