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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

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Volume 30, Issue 1

Issues

Therapeutic potential of JAK/STAT pathway modulation in mood disorders

Aisha S. Shariq
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
  • Other articles by this author:
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/ Elisa Brietzke
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
  • Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo 14021-001, Brazil
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Joshua D. Rosenblat
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
  • Department of Psychiatry, University of Toronto, Toronto, Ontario M5S 1A1, Canada
  • Other articles by this author:
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/ Zihang Pan
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
  • Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A1, Canada
  • Other articles by this author:
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/ Carola Rong
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Renee-Marie Ragguett
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
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  • De Gruyter OnlineGoogle Scholar
/ Caroline Park
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
  • Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A1, Canada
  • Other articles by this author:
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/ Roger S. McIntyre
  • Corresponding author
  • Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network (UHN), Toronto, Ontario M5T 2S8, Canada
  • Department of Psychiatry, University of Toronto, Toronto, Ontario M5S 1A1, Canada
  • Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A1, Canada
  • Brain and Cognition Discovery Foundation (BCDF), Toronto, Ontario M5T 2S8, Canada
  • Email
  • Other articles by this author:
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Published Online: 2018-06-14 | DOI: https://doi.org/10.1515/revneuro-2018-0027

Abstract

Convergent evidence demonstrates that immune dysfunction (e.g. chronic low-grade inflammatory activation) plays an important role in the development and progression of mood disorders. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is a pleiotropic cellular cascade that transduces numerous signals, including signals from the release of cytokines and growth factors. The JAK/STAT signaling pathway is involved in mediating several functions of the central nervous system, including neurogenesis, synaptic plasticity, gliogenesis, and microglial activation, all of which have been implicated in the pathophysiology of mood disorders. In addition, the antidepressant actions of current treatments have been shown to be mediated by JAK/STAT-dependent mechanisms. To date, two JAK inhibitors (JAKinibs) have been approved by the U.S. Food and Drug Administration and are primarily indicated for the treatment of inflammatory conditions such as rheumatoid arthritis. Indirect evidence from studies in populations with inflammatory conditions indicates that JAKinibs significantly improve measures of mood and quality of life. There is also direct evidence from studies in populations with depressive disorders, suggesting that JAK/STAT pathways may be involved in the pathophysiology of depression and that the inhibition of specific JAK/STAT pathways (i.e. via JAKinibs) may be a promising novel treatment for depressive disorders.

Keywords: cytokines; inflammation; JAKinib; JAK/STAT; mood disorders

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About the article

Received: 2018-03-29

Accepted: 2018-04-11

Published Online: 2018-06-14

Published in Print: 2018-12-19


Citation Information: Reviews in the Neurosciences, Volume 30, Issue 1, Pages 1–7, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2018-0027.

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