title: Stage managing bipolar disorder.
abstract: OBJECTIVE
  Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches.
  
  
  METHODS
  We provide a narrative review of the relevant information.
  
  
  RESULTS
  In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness.
  
  
  CONCLUSIONS
  The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible.
authors.affiliation: School of Medicine, Deakin University, Geelong; Department of Psychiatry, University of Melbourne, Melbourne, Vic., Australia; Orygen Youth Health, Melbourne, Vic., Australia; Florey Institute for Neuroscience and Mental Health, Melbourne, Vic., Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Lesley
authors.initials: L
authors.lastname: Berk
authors.forename: Seetal
authors.initials: S
authors.lastname: Dodd
authors.forename: Sue
authors.initials: S
authors.lastname: Cotton
authors.forename: Craig
authors.initials: C
authors.lastname: Macneil
authors.forename: Rothanthi
authors.initials: R
authors.lastname: Daglas
authors.forename: Philippe
authors.initials: P
authors.lastname: Conus
authors.forename: Andreas
authors.initials: A
authors.lastname: Bechdolf
authors.forename: Steven
authors.initials: S
authors.lastname: Moylan
authors.forename: Gin S
authors.initials: GS
authors.lastname: Malhi
mesh_terms: D001714:Bipolar Disorder / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D019468:Disease Management; D018450:Disease Progression; D006801:Humans; D011379:Prognosis
keywords: bipolar disorder; clinical staging; depression; early intervention; mania; neuroprogression; treatment