Serotonin, 5-HT_1A Serotonin Receptors and Proliferation of Lymphocytes in Major Depression Patients

Abstract

Serotonin receptors are present in lymphocytes and might be related to the functionality of these cells in health and in pathology. The serotonergic system is affected in the brain and in peripheral immune cells of depressed patients. The objectives of this work were to evaluate the basal proliferation of lymphocytes, the response to the mitogen concanavalin A, and the role of serotonin 5-HT_1A receptors. Twenty-nine patients, 19–52 years old, were diagnosed for a major depression episode with the Statistical and Diagnostic Manual-IV of the American Psychiatric Association, approved by ethic committees and gave written consent. The Hamilton depression score was 30.60 ± 2.65. An apparently healthy group without a family history of psychiatric illness was included. Blood peripheral lymphocytes were isolated by density gradients with Ficoll/Hypaque and differential adhesion to plastic, cultured in 96-well plaques with RPMI-1640 medium with or without 4 µg/ml of concanavalin A. 8-Hydroxy-2-(di-n-propylamino)tetralin (5–40 nM) and WAY-100,478 (0.1–100 µM), agonist and antagonist of 5-HT_1A receptors, serotonin (12.5–100 nM) or imipramine (0.1–100 µM) were also added. Proliferation was evaluated at 72 h with 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide, and the optical density was 570 nm. Basal proliferation was three times higher in depressed patients than in controls, whereas no response to mitogen was obtained, and 5-HT_1A receptors significantly reacted to the agonist, with increases of about 31–54% at 10, 20 and 40 nM of the specific agonist, indicating initial activation probably in relation to autoimmunity and overreactivity of these receptors in depression. The antagonist reduced proliferation in mitogen-stimulated lymphocytes, 50% in controls and 70% in depressed patients, with a differential concentration dependency; probably, these receptors are more sensitive in depression due to increased 5-HT_1A receptor transduction. The antagonist also reduced the stimulation produced by the 5-HT_1A agonist. Imipramine caused biphasic effects according to concentrations, showing a possible dual role for serotonin, although all values were significantly higher in depressed subjects. The described alterations might be of relevance in the pathophysiology of depression.

Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder

“…A wide range of cytokine-producing cells constitutively express cortisol and the serotonin receptors 5-HT 1A, 5-HT 2A, 5-HT 1B, and 5-HT 3 [29, 45, 46]. Serotonin receptors activate cAMP-dependent pathways and mediate synthesis and release of cytokines and cellular proliferation [9].…”

“…Studies of dexamethasone have reported alterations in GR in leukocytes of depressed patients, such as decreased nuclear translocation [47] and cellular proliferation [48]. In addition, lymphocytes from MDD patients have a lower density of 5-HTT [49] and impaired 5-HT 1A receptor functions [45, 46]. …”

Effect of Folic Acid Combined with Fluoxetine in Patients with Major Depression on Plasma Homocysteine and Vitamin B₁₂, and Serotonin Levels in Lymphocytes

“…Previously, increased lymphocyte proliferation probably due to 5-HT 1A receptor activation [44] , in addition to a decreased 5-HT turnover rate and a decreased number of 5-HT transporters, were reported [46] , possibly affecting the immune response mediated by these cells. If folate administration reduces homocysteine levels and also modifies the effect of 5-HT on the immune system, coadministration of folate in antidepressant treatment may be of increasing interest.…”

“…Increased levels of 5-HT in the culture medium of lymphocytes from depressed patients resulted in increased proliferation [44,45] . However, only in lymphocytes of patients receiving folic acid, a reduction in 5-HIAA was noted, probably indicating the protection of 5-HT from metabolism.…”

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD

“…Lymphocytes express 5-HT1A receptors with altered properties in depressed patients. 220 Although high doses of buspirone potentially lower immune responses, lower dosages enhance the natural killer cell activation and improve the course of viral infections in mice subjected to chronic auditory stress. 221,222 These effects in stress-induced immunomodulation may in part be due to an interaction between norepinephrine, which inhibits lymphocyte proliferation in vitro, and activation of 5-HT1A receptors, which blunt this effect.…”