Staging in bipolar disorder: from theoretical framework to clinical utility
Open accessAbstract
Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at‐risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end‐stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage‐specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage‐specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at‐risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative‐type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.
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The concepts of clinical progression and neuroprogression have provided the basis for the development of staging systems in BD.
“The concepts of clinical progression and neuroprogression have provided the basis for the development of staging systems in BD.30”
More recent evidence suggests that response to treatment is best after the first episode and declines thereafter, and this decline is associated with a potentially neuroprogressive process with substantial clinical and functional sequelae.
“More recent evidence suggests that the response to treatment is best after the first episode [34] and declines thereafter, and this decline is associated with a potentially neuroprogressive process with substantial clinical and functional sequelae [35, 36].”
From Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies (2020) · cites this paper as [36]
The clinical staging model for psychosis is the most established, but similar models also emerged for bipolar, depressive and anxiety disorders.
“The clinical staging model for psychosis is the most established 54,55 , but similar models also emerged for bipolar 56-59 , depressive 60,61 and anxiety 62-65 disorders.”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [56]
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Self-citationThe Putative Use of Lithium in Alzheimer's Disease
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Self-citationAgoraphobia Is a Disease: A Tribute to Sir Martin Roth
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Staging and psychosocial early intervention in bipolar disorder
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El cerebro visceral: trastorno bipolar y microbiota
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Self-citation
- Authors
- Berk, M., Post, R., Ratheesh, A., Gliddon, E., Singh, A., Vieta, E., Carvalho, A. F., Ashton, M. M., Berk, L., Cotton, S. M., McGorry, P. D., Fernandes, B. S., Yatham, L. N., & Dodd, S.
- Affiliations
- Deakin University (AU)
- George Washington University (US)
- The University of Melbourne (AU)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- University of Padua (IT)
- Orygen, the National Centre of Excellence in Youth Mental Health Parkville Australia
- University of British Columbia (CA)
- ORCID
- Venue
- World Psychiatry
- Publisher
- Wiley
- Published
- 2017-09-21
- Volume
- 16
- Issue
- 3
- Pages
- 236-244
- ISSN
- 1723-8617 (ISSN-L)
- 2051-5545
- PMC
- PMC5608827
- OpenAlex
- W2758822993
- Cited by
- 216
- References
- 104
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 26 · 2023: 14 · 2022: 39 · 2021: 20 · 2020: 28 · 2019: 46 · 2018: 17 · 2017: 2
- FWCI
- 20.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- World Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Health and Medical Research Council (1059660)
- ISCIII
- CIBERSAM
- NHMRC (APP1061998)
- National Institute of Mental Health
- Stanley Medical Research Institute
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
- Keywords
- bipolar disorder, prodromal symptoms, neuroprogression, clinical course, lithium, early intervention, stage-specific treatment, disease-modifying therapy, transdiagnostic model, neurogenesis, mitochondrial dysfunction, inflammation, oxidative stress, epigenetics, cognitive decline
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