Stage managing bipolar disorder
Open accessAbstract
Objectives: 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [59]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Transduction of psychosocial stress into the neurobiology of recurrent affective disorder
(1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.8.999 · Cited by 1,848 · see citing works
New insights into BDNF function in depression and anxiety
Martinowich, K., Manji, H., & Lu, B. (2007) · Nature Neuroscience · doi:10.1038/nn1971 · Cited by 1,221 · see citing works
Berk, M., Kapczinski, F., Andreazza, A. C., Dean, O. M., Giorlando, F., Maes, M., Yücel, M., Gama, C. S., Dodd, S., Dean, B., et al. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.001 · Cited by 1,178 · see citing works
Self-citationBora, E., Yücel, M., & Pantelis, C. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.06.009 · Cited by 1,021 · see citing works
McGorry, P. D., Hickie, I. B., Yung, A. R., Pantelis, C., & Jackson, H. J. (2006) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.2006.01860.x · Cited by 919 · see citing works
Scott, J., Paykel, E., Morriss, R., Bentall, R., Kinderman, P., Johnson, T., Abbott, R., & Hayhurst, H. (2006) · British Journal of Psychiatry · doi:10.1192/bjp.188.4.313 · Cited by 566 · see citing works
Robinson, L. J., & Ferrier, I. N. (2006) · Bipolar Disorders · doi:10.1111/j.1399-5618.2006.00277.x · Cited by 533 · see citing works
Moylan, S., Maes, M., Wray, N. R., & Berk, M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.33 · Cited by 529 · see citing works
Self-citationAllostatic load in bipolar disorder: Implications for pathophysiology and treatment
Kapczinski, F. P., Vieta, E., Andreazza, A. C., Frey, B. N., Gomes, F. A., Tramontina, J., Kauer‐Sant’Anna, M., Grassi‐Oliveira, R., & Post, R. M. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.10.005 · Cited by 479 · see citing works
Comparison of Standard and Low Serum Levels of Lithium for Maintenance Treatment of Bipolar Disorder
Gelenberg, A. J., Kane, J. M., Keller, M. B., Lavori, P. W., Rosenbaum, J. F., Cole, K., & Lavelle, J. (1989) · New England Journal of Medicine · doi:10.1056/nejm198911303212201 · Cited by 446 · see citing works
Kauer‐Sant’Anna, M., Kapczinski, F. P., Andreazza, A. C., Bond, D. J., Lam, R. W. M., Young, L. T., & Yatham, L. N. (2008) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145708009310 · Cited by 434 · see citing works
Strakowski, S. M., DelBello, M. P., Zimmerman, M. E., Getz, G. E., Mills, N. P., Ret, J., Shear, P. K., & Adler, C. M. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.11.1841 · Cited by 363 · see citing works
Conditioning and Sensitisation in the Longitudinal Course of Affective Illness
Post, R. M., Rubinow, D. R., & Ballenger, J. C. (1986) · The British Journal of Psychiatry · doi:10.1192/bjp.149.2.191 · Cited by 337 · see citing works
Post, R. M. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.04.003 · Cited by 303 · see citing works
Regional cerebral cortical thinning in bipolar disorder
Lyoo, I. K., Sung, Y. H., Dager, S. R., Friedman, S. D., Lee, J., Kim, S. J., Kim, N., Dünner, D. L., & Renshaw, P. F. (2006) · Bipolar Disorders · doi:10.1111/j.1399-5618.2006.00284.x · Cited by 303 · see citing works
McGorry, P. D., Nelson, B., Goldstone, S. D., & Yung, A. R. (2010) · The Canadian Journal of Psychiatry · doi:10.1177/070674371005500803 · Cited by 275 · see citing works
Clinical implications of a staging model for bipolar disorders
Kapczinski, F. P., Dias, V. V., Kauer‐Sant’Anna, M., Frey, B. N., Grassi‐Oliveira, R., Colom, F., & Berk, M. (2009) · Expert Review of Neurotherapeutics · doi:10.1586/ern.09.31 · Cited by 263 · see citing works
Self-citationStaging: a neglected dimension in psychiatric classification
Fava, G. A., & Kellner, R. (1993) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1993.tb03362.x · Cited by 252 · cited 3× · see citing works
“In 1993, Fava and Kellner (8) described staging as a “neglected dimension in psychiatric classification”.”
InfluentialSetting the stage: from prodrome to treatment resistance in bipolar disorder
Berk, M., Conus, P., Lucas, N., Hallam, K. T., Malhi, G. S., Dodd, S., Yatham, L. N., Yung, A. R., & McGorry, P. D. (2007) · Bipolar Disorders · doi:10.1111/j.1399-5618.2007.00484.x · Cited by 239 · see citing works
Self-citationSwann, A. C., Bowden, C. L., Calabrese, J. R., Dilsaver, S. C., & Morris, D. D. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.8.1264 · Cited by 231 · see citing works
López‐Jaramillo, C., Lopera-Vásquez, J. P., Gallo, A., Ospina‐Duque, J., Bell, V., Torrent, C., Martínez‐Arán, A., & Vieta, E. (2010) · Bipolar Disorders · doi:10.1111/j.1399-5618.2010.00835.x · Cited by 223 · see citing works
History of illness prior to a diagnosis of bipolar disorder or schizoaffective disorder
Berk, M., Dodd, S., Callaly, P., Berk, L., Fitzgerald, P., de Castella, A. R., Filia, S., Filia, K., Tahtalian, S., Biffin, F., et al. (2007) · Journal of Affective Disorders · doi:10.1016/j.jad.2007.01.027 · Cited by 217 · see citing works
Self-citationAndreazza, A. C., Kapczinski, F. P., Kauer‐Sant’Anna, M., Walz, J. C., Bond, D. J., Gonçalves, C. A., Young, L. T., & Yatham, L. N. (2009) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0935 · Cited by 199 · see citing works
Berk, M., Brnabic, A. J. M., Dodd, S., Kelin, K., Tohen, M. F., Malhi, G. S., Berk, L., Conus, P., & McGorry, P. D. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00889.x · Cited by 187 · see citing works
Self-citationEl-Badri, S. M., Ashton, C. H., Moore, P. B., Marsh, V. R., & Ferrier, I. N. (2001) · Bipolar Disorders · doi:10.1034/j.1399-5618.2001.030206.x · Cited by 186 · see citing works
Glutathione: a novel treatment target in psychiatry
Berk, M., Ng, F., Dean, O., Dodd, S., & Bush, A. I. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.05.001 · Cited by 183 · see citing works
Self-citationThe potential utility of a staging model as a course specifier: A bipolar disorder perspective
Berk, M., Hallam, K. T., & McGorry, P. D. (2007) · Journal of Affective Disorders · doi:10.1016/j.jad.2007.03.007 · Cited by 158 · see citing works
Self-citationBechdolf, A., Nelson, B., Cotton, S. M., Chanen, A., Thompson, A., Kettle, J., Conus, P., Amminger, G. P., Yung, A. R., Berk, M., et al. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.06.016 · Cited by 131 · see citing works
Self-citationThe impact of staging bipolar disorder on treatment outcome of family psychoeducation
Reinares, M., Colom, F., Rosa, A. R., Bonnín, C. D. M., Franco, C., Solé, B., Kapczinski, F. P., & Vieta, E. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.09.009 · Cited by 124 · see citing works
Early onset of lithium prophylaxis as a predictor of good long-term outcome
Franchini, L., Zanardi, R., Smeraldi, E., & Gasperini, M. (1999) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s004060050091 · Cited by 113 · see citing works
Leopold, K., Ritter, P. S., Correll, C. U., Marx, C., Özgürdal, S., Juckel, G., Bauer, M., & Pfennig, A. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.06.043 · Cited by 110 · see citing works
Serological observations in patients suffering from acute manic episodes
Wadee, A. A., Kuschke, R. H., Wood, L. A., Berk, M., Ichim, L., & Maes, M. H. J. (2002) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.390 · Cited by 104 · see citing works
Self-citationProgressive neurostructural changes in adolescent and adult patients with bipolar disorder
Lisy, M. E., Jarvis, K., DelBello, M. P., Mills, N. P., Weber, W. A., Fleck, D. E., Strakowski, S. M., & Adler, C. M. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00927.x · Cited by 103 · see citing works
Magalhães, P. V. D. S., Dodd, S., Nierenberg, A. A., & Berk, M. (2012) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867412460593 · Cited by 98 · see citing works
Self-citationFrom neuroprogression to neuroprotection: implications for clinical care.
Berk, M., Conus, P., Kapczinski, F. P., Andreazza, A. C., Yücel, M., Wood, S. J., Pantelis, C., Malhi, G. S., Dodd, S., Bechdolf, A., et al. (2010) · PubMed · Cited by 96 · see citing works
Self-citationLam, D. H., Burbeck, R., Wright, K. A., & Pilling, S. (2009) · Bipolar Disorders · doi:10.1111/j.1399-5618.2009.00724.x · Cited by 85 · see citing works
Rationale and First Results of Developing At-Risk (Prodromal) Criteria for Bipolar Disorder
Bechdolf, A., Ratheesh, A., J. Wood, S., Tecic, T., Conus, P., Nelson, B., M. Cotton, S., M. Chanen, A., P. Amminger, G., Ruhrmann, S., et al. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799316226 · Cited by 82 · see citing works
Self-citationFornito, A., Malhi, G. S., Lagopoulos, J., Ivanovski, B., Wood, S. J., Velakoulis, D., Saling, M. M., McGorry, P. D., Pantelis, C., & Yücel, M. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.01069.x · Cited by 62 · see citing works
Self-citationBulimia nervosa in adolescents: a disorder in evolution?
Grange, D. L., Loeb, K., Orman, S. V., & Jellar, C. C. (2004) · Archives of Pediatrics & Adolescent Medicine · doi:10.1001/archpedi.158.5.478 · Cited by 57 · see citing works
Berk, L., Jorm, A. F., Kelly, C. M., Dodd, S., & Berk, M. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00942.x · Cited by 55 · see citing works
Self-citationMacneil, C. A., Hasty, M. K., Berk, M., Henry, L. P., Evans, M., Redlich, C., Daglas, R., McGorry, P. D., & Conus, P. (2011) · Early Intervention in Psychiatry · doi:10.1111/j.1751-7893.2011.00273.x · Cited by 42 · see citing works
Self-citationMacneil, C. A., Hasty, M. K., Cotton, S., Berk, M., Hallam, K. T., Kader, L. F., McGorry, P. D., & Conus, P. (2012) · Early Intervention in Psychiatry · doi:10.1111/j.1751-7893.2011.00336.x · Cited by 41 · see citing works
Self-citationAgoraphobia Is a Disease: A Tribute to Sir Martin Roth
Fava, G. A., Rafanelli, C., Tossani, E., & Grandi, S. (2008) · Psychotherapy and Psychosomatics · doi:10.1159/000116606 · Cited by 37 · see citing works
Preventive strategies in depression: gathering evidence for risk factors and potential interventions
Berk, M., & Jacka, F. N. (2012) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.111.107797 · Cited by 34 · see citing works
Self-citationPredictors of antidepressant response: A selective review
Dodd, S., & Berk, M. (2004) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651500410005423 · Cited by 32 · see citing works
Self-citationMalhi, G. S., Chengappa, K. R., Gershon, S., & Goldberg, J. F. (2010) · Bipolar Disorders · doi:10.1111/j.1399-5618.2010.00872.x · Cited by 26 · see citing works
Self-citationAre we missing opportunities for early intervention in bipolar disorder?
Macneil, C. A., Hallam, K. T., Conus, P., Henry, L. P., Kader, L. F., & Berk, M. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.11.174 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., et al. (2018) · Bipolar Disorders · doi:10.1111/bdi.12609 · Cited by 1,852 · see citing works
Self-citationPreventive psychiatry: a blueprint for improving the mental health of young people
Fusar‐Poli, P., Correll, C. U., Arango, C., Berk, M., Patel, V., & Ioannidis, J. P. A. (2021) · World Psychiatry · doi:10.1002/wps.20869 · Cited by 497 · see citing works
Self-citationEarly Intervention in Bipolar Disorder
Vieta, E., Salagre, E., Grande, I., Carvalho, A. F., Fernandes, B. S., Berk, M., Birmaher, B., Tohen, M., & Suppes, T. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17090972 · Cited by 354 · see citing works
Self-citationFernandes, B. S., Molendijk, M. L., Köhler, C. A., Soares, J. C., Leite, C. M. G. S., Machado-Vieira, R., Ribeiro, T. L., Silva, J. C., Sales, P. M. G., Quevedo, J., et al. (2015) · BMC Medicine · doi:10.1186/s12916-015-0529-7 · Cited by 291 · see citing works
Self-citationOxidative stress in early stage Bipolar Disorder and the association with response to lithium
de Sousa, R. T., Zarate, C. A., Zanetti, M. V., Costa, A. C., Talib, L. L., Gattaz, W. F., & Machado-Vieira, R. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.11.011 · Cited by 169 · see citing works
Integrating Early Intervention for Borderline Personality Disorder and Mood Disorders
Chanen, A. M., Berk, M., & Thompson, K. (2016) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000105 · Cited by 107 · see citing works
Self-citationMurray, G., Leitan, N. D., Thomas, N., Michalak, E. E., Johnson, S. L., Jones, S., Perich, T., Berk, L., & Berk, M. (2017) · Clinical Psychology Review · doi:10.1016/j.cpr.2017.01.002 · Cited by 87 · see citing works
Self-citationPsychological therapy for anxiety in bipolar spectrum disorders: A systematic review
Stratford, H. J., Cooper, M. J., Di Simplicio, M., Blackwell, S. E., & Holmes, E. A. (2015) · Clinical Psychology Review · doi:10.1016/j.cpr.2014.11.002 · Cited by 63 · see citing works
Peters, A., Sylvia, L. G., da Silva Magalhães, P. V., Miklowitz, D. J., Frank, E., Otto, M. W., Hansen, N. S., Dougherty, D. D., Berk, M., Nierenberg, A. A., et al. (2014) · Psychological Medicine · doi:10.1017/s0033291714000804 · Cited by 41 · see citing works
Self-citationEarly interventions for youths at high risk for bipolar disorder: a developmental approach
Benarous, X., Consoli, A., Milhiet, V., & Cohen, D. (2016) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0773-6 · Cited by 35 · see citing works
- Authors
- Berk, M., Berk, L., Dodd, S., Cotton, S., Macneil, C., Daglas, R., Conus, P., Bechdolf, A., Moylan, S., & Malhi, G. S.
- Affiliations
- Deakin University (AU)
- Orygen Youth Health (AU)
- The University of Melbourne (AU)
- Centre Hospitalier Universitaire Vaudois (CH)
- University of Cologne (DE)
- The University of Sydney (AU)
- Corresponding author
- Berk, Michael
- ORCID
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2013-06-20
- Volume
- 16
- Issue
- 5
- Pages
- 471-477
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- OpenAlex
- W2088159914
- Cited by
- 163
- References
- 47
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 14 · 2019: 11 · 2018: 19 · 2017: 14 · 2016: 15 · 2015: 32 · 2014: 16 · 2013: 2
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- green
- iris.unil.ch
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- IRIS (submittedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Geelong Region Medical Research Foundation
- National Alliance for Research on Schizophrenia and Depression
- Beyond Blue
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Universität zu Köln
- Servier
- H. Lundbeck A/S
- National Health and Medical Research Council
- Cilag
- 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, clinical staging, neuroprogression, neuroprotection, first episode, illness trajectory, neuroimaging, cognitive decline, treatment response, early intervention, prevention, neuroinflammation, oxidative stress, apoptosis, neurogenesis
- MeSH terms
- Bipolar Disorder, Humans, Prognosis, Disease Progression, Disease Management
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
