Allelic Isoforms and Decrease in Serotonin Transporter mRNA in Lymphocytes of Patients with Major Depression

Abstract

Serotonin transporter, measured by the specific binding of [³H]paroxetine, has been reported to be reduced in circulating lymphocytes of patients with major depression. Due to this observation, the objective of the present report was to determine the levels of serotonin transporter mRNA in lymphocytes obtained from 29 major depression patients (4 men, age 33.10 ± 1.63 years) and from 30 subjects included as a control group (4 men, age 37.54 ± 2.18 years) using RT-PCR. The patients were diagnosed according to the criteria of the American Psychiatric Association, and had a severity of depression of 32.68 ± 1.55 determined by the Hamilton Rating Scale for Depression. The DNA was submitted to polymerase chain reaction with primers for the 5′ regulatory region of human serotonin transporter, which could show the long and the short allelic forms of the transporter gene for the 5HTTLPR polymorphism. Semiquantitative analysis was performed using β-actin as internal and external standard. Control subjects presented the two allelic forms in 9.09% and depressed patients in 8.69%. The long variant was present in 73% of controls and in 60% of patients, without significant differences. There was a significant reduction in mRNA in depressed patients expressing the long allele. The number of immunofluorescent lymphocytes, labeled with a specific antibody against serotonin transporter, was reduced in the patients, as well as CD3+ lymphocytes. Serotonin and 5-hydroxyindoleacetic acid in platelet-poor plasma or lymphocytes did not differ between depressed patients and controls. The reduction in lymphocyte serotonin transporter described in major depression might be due to a decrease in the level of its mRNA and in the number of cells expressing it. These observations might implicate that functional modifications are associated with nervous-immune interactions in depression.

The role of IL-12 and TGF-β1 in the pathophysiology of major depressive disorder

“…Several possible mechanisms have been proposed, although evidence in support of these theories is still limited [17,42]. First, changes in immune reactivity and (central) cytokine action observed after antidepressant treatment may be secondary to the neurotransmitter changes that are induced by these antidepressants, as brain-to-immune communication is assumed to be exerted, at least in part, through central monoaminergic signaling [42][43][44][45][46]. Second, antidepressants may also reverse cytokine-induced alterations in central corticosteroid receptor expression and responsivity, thereby discontinuing cytokine-induced corticosteroid receptor resistance in the hypothalamus and pituitary gland.…”

Long-Term Behavioral Changes After Cessation of Chronic Antidepressant Treatment in Olfactory Bulbectomized Rats

“…The exact mechanism for this delay in action is as of yet unknown, but it has been hypothesized that it might be due to down-regulation of certain neurotransmitter receptors in the brain (Lima et al 2002;Lloyd et al 1987). Another theory, according to research using chronic restraint stress by Chen et al (2005), is that this delay is due to the time it takes for the promotion of neurogenesis in the hippocampus, which they observed after 21 days of antidepressant treatment.…”

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.…”