Serotonin 2A receptor clustering in peripheral lymphocytes is altered in major depression and may be a biomarker of therapeutic efficacy

Abstract

Background: In a previous report, we showed that the clustering of serotonin (5HT) transporter (SERT) protein on cell membranes of peripheral lymphocytes predicts responsivity to antidepressant medication in two subpopulations of naïve depression patients (Rivera-Baltanas et al., J Affect Disord, 2012, 137, 46-55). In this study, we extended this idea to 5-HT2A receptor clusters in a similar patient population.

Methods: We collected blood samples from a subset of patients from our previous study on SERT clustering (20 untreated and newly diagnosed depression patients, and 20 matched control subjects). Blood samples were collected at the time of diagnosis and after 8 weeks of pharmacological treatment and at analogous times in control subjects. We used the Hamilton scale to quantify the level of depression in patients both before and after treatment. We then used immunocytochemistry to assess 5-HT2A receptor clusters in lymphocytes at the same time points.

Results: We found that both the size and number of 5-HT2A receptor clusters were increased in naïve depression patients compared to control subjects. Interestingly, there were individual differences in the distribution of 5-HT2A receptor cluster size that allowed us to differentiate the depression patients into two subgroups: a D-I group and a D-II group. After 8 weeks of pharmacological treatment, patients in both groups showed an improvement of symptoms, but patients in the D-II group had a much better outcome with many of them showing remission of symptoms. Furthermore, although treatment decreased cluster number and size in both D-I and D-II groups, only the D-II patients showed an increase in the number of clusters within the modal peak. Importantly, the same patients that belonged in the D-I or D-II groups in the present report were also assigned to the same groups in our previous study on SERT clustering.

Limitations: The data should be replicated within a proper clinical trial.

Conclusions: 5-HT2A receptor clusters in peripheral lymphocytes are altered in major depression, partially reversed by antidepressant treatment, and may be considered a putative biomarker of therapeutic efficacy in major depression.

Keywords: 5-HT2A receptor; Membrane protein clustering; Mood disorders; Peripheral biomarkers; Translational psychiatry.