Influence of birth cohort on age of onset cluster analysis in bipolar I disorder
Open accessAbstract
Purpose: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. Methods: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. Results: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. Conclusion: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
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Bipolar disorder frequently manifests in late adolescence and young adulthood, with an overall average age of onset of 25 years.
“Bipolar disorder frequently manifests in late adolescence and young adulthood, with an overall average age of onset of 25 years.”
From Canadian Network for Mood and Anxiety Treatments ( <scp>CANMAT</scp> ) and International Society for Bipolar Disorders ( <scp>ISBD</scp> ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [8]
Section 2.2 reports an unadjusted mean onset age of 25.4 years among 4,037 patients with bipolar I disorder. The Results also identify a younger-onset subgroup with a mean of 20.7 years, supporting frequent onset in late adolescence or young adulthood. The cited analysis excludes bipolar II and bipolar NOS, so it does not establish an overall average for bipolar disorder broadly. (LLM, conf=0.85)
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“Secondly, the proportion of participants included in age at onset subgroups can be influenced by recall bias and study design,(33) as well as by sample characteristics, including geographic location(34,35) and birth cohort.(36,37) In an effort to overcome such limitations, the current study analyzes data from a large,…”
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- Authors
- Bauer, M., Glenn, T., Alda, M., Andreassen, O. A., Angelopoulos, E., Ardau, R., Baethge, C., Bauer, R., Bellivier, F., Belmaker, R. H., Berk, M., Bjella, T. D., Bossini, L., Bersudsky, Y., Cheung, E. Y. W., Conell, J., Del Zompo, M., Dodd, S., Etain, B., Fagiolini, A., Frye, M. A., Fountoulakis, K. N., Garneau-Fournier, J., Gonzalez-Pinto, A., Harima, H., Hassel, S., Henry, C., Iacovides, A., Isometsä, E. T., Kapczinski, F., Kliwicki, S., König, B., Krogh, R., Kunz, M., Lafer, B., Larsen, E. R., Lewitzka, U., Lopez-Jaramillo, C., MacQueen, G., Manchia, M., Marsh, W., Martinez-Cengotitabengoa, M., Melle, I., Monteith, S., Morken, G., Munoz, R., Nery, F. G., O’Donovan, C., Osher, Y., Pfennig, A., Quiroz, D., Ramesar, R., Rasgon, N., Reif, A., Ritter, P., Rybakowski, J. K., Sagduyu, K., Scippa, A. M., Severus, E., Simhandl, C., Stein, D. J., Strejilevich, S., Hatim Sulaiman, A., Suominen, K., Tagata, H., Tatebayashi, Y., Torrent, C., Vieta, E., Viswanath, B., Wanchoo, M. J., Zetin, M., & Whybrow, P. C.
- Affiliations
- University Hospital Carl Gustav Carus (DE)
- Dalhousie University (CA)
- Oslo University Hospital (NO)
- National and Kapodistrian University of Athens (GR)
- Azienda Ospedaliero-Universitaria Cagliari (IT)
- University of Cologne (DE)
- Inserm (FR)
- Ben-Gurion University of the Negev (IL)
- Deakin University (AU)
- University of Siena (IT)
- Castle Peak Hospital (CN)
- Mayo Clinic (US)
- Stanford Medicine (US)
- Tokyo Metropolitan Matsuzawa Hospital (JP)
- University of Calgary (CA)
- Aristotle University of Thessaloniki (GR)
- University of Helsinki (FI)
- Universidade Federal do Rio Grande do Sul (BR)
- Poznan University of Medical Sciences (PL)
- Aarhus University Hospital (DK)
- Universidade de São Paulo (BR)
- University of Massachusetts Chan Medical School (US)
- Michigan State University (US)
- Norwegian University of Science and Technology (NO)
- University of California San Diego (US)
- Universidad Diego Portales (CL)
- University of Cape Town (ZA)
- Goethe University Frankfurt (DE)
- University of Missouri–Kansas City (US)
- Favaloro University (AR)
- City of Helsinki (FI)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- National Institute of Mental Health and Neurosciences (IN)
- Chapman University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Bauer, M.
- ORCID
- Bauer, M.
- Glenn, T.
- Alda, M.
- Andreassen, O.A.
- Ardau, R.
- Baethge, C.
- Bellivier, F.
- Belmaker, R.H.
- Bjella, T.D.
- Dodd, S.
- Fagiolini, A.
- Frye, M.A.
- Hassel, S.
- Henry, C.
- Isometsä, E.T.
- Kapczinski, F.
- Kliwicki, S.
- König, B.
- Kunz, M.
- Lafer, B.
- Larsen, E.R.
- Lewitzka, U.
- MacQueen, G.
- Manchia, M.
- Marsh, W.
- Melle, I.
- Monteith, S.
- Morken, G.
- Nery, F.G.
- O’Donovan, C.
- Osher, Y.
- Pfennig, A.
- Quiroz, D.
- Ramesar, R.
- Rasgon, N.
- Reif, A.
- Ritter, P.
- Rybakowski, J.K.
- Severus, E.
- Simhandl, C.
- Stein, D.J.
- Strejilevich, S.
- Tagata, H.
- Tatebayashi, Y.
- Torrent, C.
- Vieta, E.
- Viswanath, B.
- Venue
- European Psychiatry
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-01
- Volume
- 30
- Issue
- 1
- Pages
- 99-105
- ISSN
- 0924-9338 (ISSN-L)
- 1778-3585
- OpenAlex
- W2038962522
- Cited by
- 39
- References
- 49
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 4 · 2013: 1
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- European Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Aston Publications Explorer (Aston University) (submittedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (64410)
- Research Council of Norway (213837; 223273; 217776, Grant numbers ES488722, ES421716)
- South-East Norway Health Authority (2013-123)
- NHMRC Senior Principal Research Fellowship (M Berk, Grant number 1059660; INSERM (BE, Grant number C0829) and APHP (BE, Grant number AOR11096)
- Spanish Government (AGP, Grant numbers PS09/02002 CIBER Network; EC10-333, PI10/01430, PI10/01746, PI11/01977, PI11/02708, 2011/1064, 11-BI-01, 1677-DJ-030, EC10-220)
- European Regional Development Funds (UE/2012/FI-STAR, UE/2013/TENDERMH, UE/2013/MASTERMIND)
- grants from Spanish Government (PI10/01430, PI10/01746, EC10-220, EC10-333, PI11/01977, 20111064, PI11/02708, PI12/02077, PI13/02252, PI13/00451)
- Basque Government (200911147, 2010111170, 2010112009, 2011111110, 2011111113)
- Basque Foundation for Health Innovation and Research (BIO12/AL/002)
- Spanish Clinical Research Network (CAIBER;1392-D-079)
- University of the Basque Country (IT679-13)
- Stanley Research Foundation (03-RC-003)
- Regional Health Authority of South Eastern Norway (2011085, 2013088)
- DFG (SFB TRR 58, B06, Z02)
- DFG and Länder funds (RTG1252/2)
- Medical Research Council of South Africa (DJS); Spanish Ministry of Economy and Competitiveness (PI12/00912, PN 2008-2011)
- nstituto de Salud Carlos III- Subdirección General de Evaluación y Fomento de la Investigación (EV); Fondo Europeo de Desarrollo Regional Unión Europea. Una manera de hacer Europa (EV); CIBERSAM (EV); the Comissionat per a Universitats i Recerca del DIUE de la Generalitat de Catalunya to the Bipolar Disorders Group (2009 SGR 1022)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- bipolar I disorder, age of onset, birth cohort effects, model-based clustering, mixture analysis, family history of mood disorders, generalized estimating equations
- MeSH terms
- Adult, Aged, Bipolar Disorder, Female, Humans, International Cooperation, Male, Middle Aged, Global Health, Cohort Studies, Cluster Analysis, Databases, Factual, Age of Onset, Mood Disorders
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