Serotonin transporter clustering in blood lymphocytes as a putative biomarker of therapeutic efficacy in major depressive disorder.

Background: Serotonin transporter (SERT) binding is decreased in lymphocytes of depression patients and this decrease is partially reversed by antidepressant medication. However, recent evidence has shown that clustering of SERT on cell membranes is very important for receptor functionality. Alteration in SERT clustering on peripheral lymphocytes does not affect symptoms severity. At the most it is associated or predicts responsivity to treatment.

Methods: We collected blood samples from 38 untreated and newly diagnosed depression patients at the time of diagnosis and after 8weeks of pharmacological treatment and of 38 control subjects. We used the Hamilton Scale to quantify the level of depression in patients both before and after pharmacological treatment. We then used immunocytochemistry to assess SERT protein clusters in lymphocyte blood samples.

Results: We found an increase in SERT cluster size, but not the number of SERT clusters, in naïve depression patients compared to control subjects. Based on the distribution of SERT cluster size we differentiated the naïve depression patients into two groups (D-I and D-II). Naïve D-I and D-II patients initially showed similar Hamilton scores. However, after pharmacological treatment the D-II patients showed a greater decrease in Hamilton scores than did the D-I patients, and they had an increase in the number of SERT clusters.

Limitations: The data should be replicated in a larger cohort of patients and with a proper clinical trial.

Conclusions: We propose that SERT clustering in blood lymphocytes may be a putative biomarker for antidepressant efficacy in major depressive disorder.