title: Staging and neuroprogression in bipolar disorder.
abstract: 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.
authors.affiliation: Laboratory of Molecular Psychiatry, Centro de Pesquisas Experimentais, Hospital de Clínicas de Porto Alegre, and INCT for Translational Medicine, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil. gabrielrfries@gmail.com
authors.forename: Gabriel Rodrigo
authors.initials: GR
authors.lastname: Fries
authors.forename: Bianca
authors.initials: B
authors.lastname: Pfaffenseller
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.forename: André Vinicius Contri
authors.initials: AV
authors.lastname: Paz
authors.forename: Aroldo Ayub
authors.initials: AA
authors.lastname: Dargél
authors.forename: Maurício
authors.initials: M
authors.lastname: Kunz
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
mesh_terms: D052636:Allostasis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D001714:Bipolar Disorder / Q000235:genetics / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D018450:Disease Progression; D006801:Humans; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D015415:Biomarkers