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


CONCLUSIONS
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.
Department of Cell Biology, University of Santiago de Compostela, Spain; Hospital Meixoeiro, CHUVI, Vigo, Spain.
Tania
T
Rivera-Baltanas
Hospital Meixoeiro, CHUVI, Vigo, Spain.
Jose Manuel
JM
Olivares
Hospital Meixoeiro, CHUVI, Vigo, Spain.
Jose Ramon
JR
Martinez-Villamarin
Department of Psychology, University of Saskatchewan, Saskatoon, SK, Canada.
Erin Y
EY
Fenton
Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Lisa E
LE
Kalynchuk
Department of Cell Biology, University of Santiago de Compostela, Spain; College of Pharmacy and Nutrition, University of Saskatchewan, Academic Health Sciences Bldg # 1B23, 107 Wiggins Road, Saskatoon, Saskatoon, SK, Canada S7N 5E5. Electronic address: hector.caruncho@usask.ca.
Hector J
HJ
Caruncho
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003865:Major Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D021381:Protein Transport; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000097:blood*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D015415:Biomarkers; D044402:Receptor, Serotonin, 5-HT2A
5-HT2A receptor; Membrane protein clustering; Mood disorders; Peripheral biomarkers; Translational psychiatry