PPP3CC gene: a putative modulator of antidepressant response through the B-cell receptor signaling pathway.
Antidepressant pharmacogenetics represents a stimulating, but often discouraging field. The present study proposes a combination of several methodologies across three independent samples. Genes belonging to monoamine, neuroplasticity, circadian rhythm and transcription factor pathways were investigated in two samples (n=369 and 88) with diagnosis of major depression who were treated with antidepressants. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) genome-wide study (n=1861). Top genes were further studied through a pathway analysis. In both original samples, markers associated with outcomes were concentrated in the PPP3CC gene. Other interesting findings were particularly in the HTR2A gene in one original sample and the STAR*D. The B-cell receptor signaling pathway proved to be the putative mediator of PPP3CC's effect on antidepressant response (P=0.03). Among innovative candidates, PPP3CC, involved in the regulation of immune system and synaptic plasticity, seems promising for further investigation.
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
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Fabbri
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
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Marsano
Unit of Genetics of Neurodegenerative Disorders, Neuroscience Department, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
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Albani
Unit of Genetics of Neurodegenerative Disorders, Neuroscience Department, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
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Chierchia
Laboratoire de Psychologie Medicale, Université Libre de Bruxelles and Psy Pluriel, Centre Europeén de Psychologie Medicale, Brussels, Belgium.
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Calati
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
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000000015633231X
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Drago
Department of Biomedical Science and Morphological and Functional Images, University of Messina, Messina, Italy.
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Crisafulli
1] Department of Biomedical Science and Morphological and Functional Images, University of Messina, Messina, Italy [2] IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy [3] Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
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Calabrò
Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria.
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Kasper
Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria.
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Lanzenberger
Department of Psychiatry, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Zohar
Department of Psychiatry, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Juven-Wetzler
Laboratoire de Psychologie Medicale, Universitè Libre de Bruxelles and Psy Pluriel, Centre Européen de Psychologie Medicale, Brussels, Belgium.
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Souery
School of Medicine, Imperial College, London, UK.
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Montgomery
Laboratoire de Psychologie Medicale, Université Libre de Bruxelles and Psy Pluriel, Centre Europeén de Psychologie Medicale, Brussels, Belgium.
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Mendlewicz
1] Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy [2] IRCCS Centro S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
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Serretti
D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000928:Antidepressive Agents; D011947:Receptors, Antigen, B-Cell; D019703:Calcineurin; C525675:PPP3CC protein, human