Allelic isoforms and decrease in serotonin transporter mRNA in lymphocytes of patients with major depression.

Serotonin transporter, measured by the specific binding of [(3)H]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 5 HTTLPR polymorphism. Semiquantitative analysis was performed using beta-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.