Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients

S. Rzezniczek*, M. Obuchowicz, W. Datka, M. Siwek, D. Dudek, K. Kmiotek, K. Oved, N. Shomron, D. Gurwitz, A. Pilc

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Major depression disorder (MDD) is the most widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are used as first-line MDD treatment but are effective in o70% of patients. Thus, biomarkers for the early identification of treatment-resistant (TR) MDD patients are needed for prioritizing them for alternative therapeutics. SSRI-induced inhibition of the growth of peripheral blood mononuclear cells (PBMCs) is mediated via their target, the serotonin transporter (SERT). Here, we examined whether antidepressant drug-induced inhibition of the growth of PBMCs differed between MDD patients and healthy controls. PBMCs from well-characterized 33 treatment-sensitive (TS) and 33 TR MDD patients, and 24 healthy volunteers were studied. Dose-dependent inhibition of PBMCs growth was observed for both the non-SSRI antidepressant mirtazapine and the SSRI antidepressant paroxetine. Significantly lower sensitivities to 20 μ M paroxetine were observed in MDD compared with control PBMCs prior to treatment onset (13% and 46%, respectively; Po0.05). Following antidepressant drug treatment for 4 or 7 weeks, the ex vivo paroxetine sensitivity increased to control levels in PBMCs from TS but not from TR MDD patients. This suggests that the low ex vivo paroxetine sensitivity phenotype reflects a state marker of depression. A significantly lower expression of integrin beta-3 (ITGB3), a co-factor of the SERT, was observed in the PBMCs of MDD patients prior to treatment onset compared with healthy controls, and may explain their lower paroxetine sensitivity. Further studies with larger cohorts are required for clarifying the potential of reduced PBMCs paroxetine sensitivity and lower ITGB3 expression as MDD biomarkers.

Original languageEnglish
Article numbere827
JournalTranslational Psychiatry
Volume6
Issue number5
DOIs
StatePublished - 2016

Funding

FundersFunder number
Amedee Maratier Institute for the Study of Blindness
CBRN
Consortium for Mapping Retinal Degeneration Disorders in Israel
Faculty of Medicine at Tel Aviv University
Israeli Ministry of Science, Technology and Space on the Science, Technology and Innovation
Margot Stoltz Foundation
Office of Assistant Minister of Defense for Chemical, Biological, Radiological and Nuclear
Sagol School of Neuroscience
Varda and Boaz Dotan Research Center in Hemato-Oncology
Wolfson Family Charitable Fund
Yoran Institute for Human Genome Research
Israel Cancer Research Fund
Melanoma Research Alliance
Gamba Family Foundation
United States-Israel Binational Science Foundation
Israel Cancer Association
Israel Science Foundation41/11
Tel Aviv University
Ministerstwo Nauki i Szkolnictwa Wyższego
Ministero degli Affari Esteri e della Cooperazione Internazionale
Ministry of Defense

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