Current Psychiatry Reports

, Volume 14, Issue 6, pp 667–675 | Cite as

Staging and Neuroprogression in Bipolar Disorder

  • Gabriel Rodrigo Fries
  • Bianca Pfaffenseller
  • Laura Stertz
  • André Vinicius Contri Paz
  • Aroldo Ayub Dargél
  • Maurício Kunz
  • Flávio Kapczinski
Bipolar Disorders (MA Frye, Section Editor)


The apparently progressive nature of a considerable proportion of cases of bipolar disorder (BD) has been acknowledged in recently proposed clinical staging models. This has been part of an attempt to facilitate and refine diagnosis, treatment selection, and establish a prognosis. The study of the progressive nature of some cases of BD has given raise to the hypothesis of neuroprogression, which postulates that different stages of BD are associated with distinct neurobiological underpinnings. Given that BD may be intimately associated with chronic stress response and coping mechanisms over the course of illness, we propose that cellular resilience mechanisms may play a key role in the neuroprogression in BD. In the present study, we review neuroanatomical evidence of the progression that occurs in many cases of BD, as well as cellular resilience mechanisms and peripheral biomarkers associated with distinct stages of this disorder. In summary, cellular resilience mechanisms seem to be less efficient at later stages of BD, especially mitochondrial and endoplasmic reticulum-related responses to stress. These insights may help in developing staging models of BD, with a special emphasis on the search for biomarkers associated with illness progression.


Bipolar disorder BD Staging Clinical staging model Neuroprogression Cellular resilience Neuroplasticity Biomarkers Allostatic load Treatment Remission Psychiatry 



G. R. Fries: none; B. Pfaffenseller: none; L. Stertz: none; A. V. C. Paz: none; A. Ayub Dargél: none; M. Kunz: travel/accommodations/meeting expenses reimbursed by Eli Lilly and Company; F. Kapczinski: grants from NARSAD, Stanley Medical Research Institute, CNPq (National Council for Scientific and Technological Development), and CAPES, and payment for lectures including service on speakers bureaus from Eli Lilly and Company, Lundbeck, AstraZeneca, Servier, and Janssen.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Gabriel Rodrigo Fries
    • 1
    • 2
  • Bianca Pfaffenseller
    • 1
    • 2
  • Laura Stertz
    • 1
    • 2
  • André Vinicius Contri Paz
    • 1
  • Aroldo Ayub Dargél
    • 1
    • 3
  • Maurício Kunz
    • 1
    • 3
  • Flávio Kapczinski
    • 1
    • 2
    • 3
  1. 1.Laboratory of Molecular Psychiatry, Centro de Pesquisas ExperimentaisHospital de Clínicas de Porto Alegre, and INCT for Translational MedicinePorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em Ciências Biológicas: BioquímicaUniversidade Federal do Rio Grande do Sul, UFRGSPorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em Medicina: PsiquiatriaUniversidade Federal do Rio Grande do Sul, UFRGSPorto AlegreBrazil

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