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Preliminary evidence that early reduction in p11 levels in natural killer cells and monocytes predicts the likelihood of antidepressant response to chronic citalopram

Molecular Psychiatry volume 19, pages 962–964 (2014)Cite this article

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The prediction of treatment response in many neuropsychiatric disorders would be facilitated by easily accessible biomarkers. Using flow cytometry, we herein demonstrate correlations between early reduction in p11 levels in natural killer (NK) cells and monocytes, and antidepressant response to citalopram in patients with major depressive disorder (MDD).

The multifunctional protein p11 amplifies serotonin receptor-mediated signaling1,2 and regulates gene transcription.3,4 P11 levels are reduced in neurons of the frontal cortex, nucleus accumbens and hippocampus from depressed individuals and suicide victims.1,5 Neuronal p11 levels are also reduced in animal models of depression,1 but are upregulated by various antidepressant treatments, including selective serotonin reuptake inhibitors.1,6 P11 knockout mice show a depression-like phenotype and reduced behavioral improvements and neurogenesis in response to antidepressant regimens.6,7 Conversely, overexpression of p11 in mice mimics the behavioral phenotype seen after antidepressant treatment.1 Here, we examined the possibility that p11 in white blood cells could serve as a biomarker of antidepressant response using the selective serotonin reuptake inhibitor, citalopram.

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Acknowledgements

This study was supported in part by the Intramural Research Program of the National Institute of Mental Health (DM, DFI, ER, MN, AM, HM, CAZ), National Institutes of Health (IRP-NIMH-NIH), by NIMH MH090963 (PG), JPB Foundation (PG), Fisher Center for Alzheimer’s research Foundation (PG, PS) and by the Swedish Medical Research Council (PS).

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  1. H Manji

    Present address: 6Current address: Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ, USA.,

Authors and Affiliations

  1. Department of Clinical Neuroscience, Stockholm, Sweden

    P Svenningsson

  2. Department of Medicine, Karolinska Institute, Stockholm, Sweden,

    L Berg

  3. Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA

    D Matthews, D F Ionescu, E M Richards, M J Niciu, A Malinger, H Manji & C A Zarate Jr

  4. Department of Psychiatry and the Mood Disorders Research Program and Clinic, University of Texas Southwestern Medical Center, Dallas, TX, USA

    M Toups & M H Trivedi

  5. Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA

    P Greengard

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  1. P Svenningsson
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  2. L Berg
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  3. D Matthews
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  7. A Malinger
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  8. M Toups
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  9. H Manji
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  11. C A Zarate Jr
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  12. P Greengard
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Corresponding authors

Correspondence to P Svenningsson or P Greengard.

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Competing interests

Drs Svenningsson and Greengard are coinventors of an issued patent for usage of p11 to study depression and antidepressant responses. This patent was licensed by The Rockefeller University to Intracellular Therapies, for which Drs Svenningsson and Greengard serve as consultants. Dr Manji is an employee at Johnson & Johnson. Dr Trivedi is or has been an advisor/consultant to several pharmaceutical companies (listed in the Supplementary Material). Dr Zarate is listed as a coinventor on a patent application for the use of ketamine and its metabolites in major depression. Dr Zarate has assigned his rights in the patent to the US government but will share a percentage of any royalties that may be received by the government. The remaining authors declare no conflict of interest.

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Svenningsson, P., Berg, L., Matthews, D. et al. Preliminary evidence that early reduction in p11 levels in natural killer cells and monocytes predicts the likelihood of antidepressant response to chronic citalopram. Mol Psychiatry 19, 962–964 (2014). https://doi.org/10.1038/mp.2014.13

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