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Blood Mononuclear Cell Proteome Suggests Integrin and Ras Signaling as Critical Pathways for Antidepressant Treatment Response

Published:February 06, 2014DOI:https://doi.org/10.1016/j.biopsych.2014.01.022
      The antidepressant medications that are presently available often induce undesirable side effects and show only modest efficacy: about 40% of patients with major depressive disorder (MDD) do not respond adequately to treatment (
      • Fava G.A.
      Subclinical symptoms in mood disorders: Pathophysiological and therapeutic implications.
      ). Biochemical understanding regarding the delayed therapeutic response as well as the high rates of relapse and treatment resistance is limited (
      • Rosenzweig-Lipson S.
      • Beyer C.E.
      • Hughes Z.A.
      • Khawaja X.
      • Rajarao S.J.
      • Malberg J.E.
      • et al.
      Differentiating antidepressants of the future: Efficacy and safety.
      ). Also, there are no biomarkers that can indicate whether a given antidepressant treatment will be effective (
      • Martins-de-Souza D.
      Biomarkers for psychiatric disorders: Where are we standing?.
      ,
      • Labermaier C.
      • Masana M.
      • Mueller M.
      Biomarkers predicting antidepressant treatment response: How can we advance the field?.
      ). Proteomics is a suitable tool to address these questions (
      • Oliveira B.M.
      • Schmitt A.
      • Falkai P.
      • Martins-de-Souza D.
      Is clinical proteomics heading towards to “bench to bedside”?.
      ). We employed liquid chromatography–tandem mass spectrometry for profiling the proteomes of blood mononuclear cells (MNCs) collected in vivo from inpatients with MDD upon admission to the clinic (T0) and after 6 weeks of antidepressant treatment (T6). In contrast to brain tissue specimens, MNCs are available in vivo and are known to express many proteins that are also expressed in the brain. First, we compared proteomes of responders and nonresponders at T0 to identify molecular profiles that can predict a successful response, with follow-up at T6. Second, T0 and T6 proteomes of responders and of nonresponders were compared to reveal molecular pathways associated with therapy response.
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