Normal lymphocyte responsiveness to lectins but impaired sensitivity to in vitro glucocorticoids in major depression

doi:10.1016/0165-0327(91)90070-9

Journal of Affective Disorders

Volume 22, Issue 4, August 1991, Pages 241-248

https://doi.org/10.1016/0165-0327(91)90070-9 Get rights and content

Abstract

The mitogen-induced lymphocyte proliferative response and its sensitivity to in vitro (10^-10–10^-6 M) dexamethasone (DEX) administration were investigated in 12 severely depressed patients and 13 healthy controls. Patients with major depressive disorder exhibited no impairment of lectin-induced blastogenesis, but a significantly weaker suppressive effect of in vitro DEX on 1.0 μg/ml phytohemagglutinin A-induced proliferation. The inhibitory potency of in vitro DEX was inversely correlated with in vivo adrenal cortical hormone levels at 4.00 p.m. These effects were not observed with pokeweed mitogen- and concanavalin A-stimulated cells. There were no correlations with age, weight, sex or severity of depression. These results do not support the hypothesis of a primarily impaired cell-mediated immunity, but might be indicative of reduced glucocorticoid receptor sensitivity in major depressive disorder.

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The GR resistance associated with lower glucocorticoid feedback sensitivity in depressed patients is apparent in reduced GR function in leukocytes reflected by decreased nuclear translocation after DEX exposure (38) and diminished DEX-induced inhibition of mitogen-associated PBMC proliferation (39). Glucocorticoid resistance in peripheral immune cells seen in depression correlates with glucocorticoid resistance in the DEX suppression test (40). The obvious contrast between these findings and the evidence for enhanced GR sensitivity in PTSD is particularly interesting considering the frequent comorbidity of depression and PTSD.
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Lower NR3C1-1_F promoter methylation in peripheral blood mononuclear cells (PBMCs) was observed in combat veterans with PTSD compared with combat-exposed veterans who did not develop PTSD. NR3C1-1_F promoter methylation was also associated with three functional measures of glucocorticoid activity that have been associated with PTSD in combat veterans: PBMCs’ lysozyme inhibition on the lysozyme suppression test, plasma cortisol decline on the low-dose (.50 mg) dexamethasone suppression test, and 24-hour urinary cortisol excretion. Finally, NR3C1-1_F promoter methylation was inversely correlated with clinical markers and symptoms associated with PTSD.
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Icaritin opposes the development of social aversion after defeat stress via increases of GR mRNA and BDNF mRNA in mice
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Impaired glucocorticoid sensitivity has been observed in social defeat models and depressed patients [19,20]. Studies on immune cells from peripheral blood have shown that the capacity of glucocorticoids to inhibit proliferation of PBMCs in response to polyclonal mitogens is impaired in depressed patients [21–23]. In this study we demonstrated that corticosterone concentrations that reduced viability of spleen cells from control mice had little effect on the viability of cells from social defeated mice.
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Normal lymphocyte responsiveness to lectins but impaired sensitivity to in vitro glucocorticoids in major depression

Abstract

Psychiatry Res.

Psychiatry Res.

J. Affect. Disord.

Biol. Psychiatry

Life Sci.

Biol. Psychiatry

Mol. Brain Res.

Biol. Psychiatry

Interactions between the brain and the immune system

Annu. Rev. Pharmacol. Toxicol.

Lymphocyte function in major depression

Acta Psychiatr. Scand.

Diagnostic and Statistical Manual of Mental Disorders

Selective suppressive effects of glucocorticoids on the early events in the human B cell activation process

J. Immunol.

Alterations in immunocompetence during stress, bereavement, and depression: focuses on neuroendocrine regulation

Am. J. Psychiatry

Resistance to suppression by dexamethasone of plasma 11-OHCS levels in severe depressive illness

Br. Med. J.

Corticosteroid-mediated immunoregulation in man

Immunol. Rev.