M Bauer1, T Glenn2, M Alda3, O A Andreassen4, E Angelopoulos5, R Ardau6, C Baethge7, R Bauer8, F Bellivier9, R H Belmaker10, M Berk11, T D Bjella4, L Bossini12, Y Bersudsky10, E Y W Cheung13, J Conell8, M Del Zompo14, S Dodd15, B Etain16, A Fagiolini12, M A Frye17, K N Fountoulakis18, J Garneau-Fournier19, A Gonzalez-Pinto20, H Harima21, S Hassel22, C Henry16, A Iacovides18, E T Isometsä23, F Kapczinski24, S Kliwicki25, B König26, R Krogh27, M Kunz24, B Lafer28, E R Larsen27, U Lewitzka8, C Lopez-Jaramillo29, G MacQueen22, M Manchia3, W Marsh30, M Martinez-Cengotitabengoa20, I Melle4, S Monteith31, G Morken32, R Munoz33, F G Nery28, C O'Donovan3, Y Osher10, A Pfennig8, D Quiroz34, R Ramesar35, N Rasgon19, A Reif36, P Ritter8, J K Rybakowski25, K Sagduyu37, A M Scippa38, E Severus8, C Simhandl26, D J Stein39, S Strejilevich40, A Hatim Sulaiman41, K Suominen42, H Tagata21, Y Tatebayashi43, C Torrent44, E Vieta44, B Viswanath45, M J Wanchoo17, M Zetin46, P C Whybrow47. 1. Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany Fetscherstr, 74, 01307 Dresden, Germany. Electronic address: michael.bauer@uniklinikum-dresden.de. 2. ChronoRecord Association, Fullerton, CA, USA. 3. Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. 4. NORMENT - K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Oslo, Norway. 5. Department of Psychiatry, University of Athens Medical School, Eginition Hospital, Athens, Greece. 6. Unit of Clinical Pharmacology, University Hospital of Cagliari, Cagliari, Italy. 7. Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne, Germany. 8. Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany Fetscherstr, 74, 01307 Dresden, Germany. 9. Psychiatrie, GH Saint-Louis - Lariboisière - F.-Widal, AP-HP, INSERM UMR-S1144, Faculté de Médecine, Université D.-Diderot, Paris, France; FondaMental Fondation, Créteil, France. 10. Department of Psychiatry, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva Mental Health Center, Beer Sheva, Israel. 11. IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria 3220, Australia; Department of Psychiatry, ORYGEN Youth Health Research Centre, Centre for Youth Mental Health and the Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3052, Australia. 12. Department of Molecular Medicine and Department of Mental Health (DAI), University of Siena and University of Siena Medical Center (AOUS), Siena, Italy. 13. Department of General Adult Psychiatry, Castle Peak Hospital, Hong Kong. 14. Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy. 15. IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria 3220, Australia; Department of Psychiatry, University of Melbourne, Parkville, Victoria 3052, Australia. 16. AP-HP, Hôpitaux Universitaires Henri-Mondor, INSERM U955 (IMRB), Université Paris Est, and FondaMental Fondation, Créteil, France. 17. Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA. 18. 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. 19. Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Palo Alto, CA, USA. 20. Department of Psychiatry, University Hospital of Alava, University of the Basque Country, CIBERSAM, Vitoria, Spain. 21. Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan. 22. Department of Psychiatry, Faculty of Medicine, University of Calgary, Calgary, AB, Canada. 23. Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland. 24. Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 25. Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. 26. BIPOLAR Zentrum Wiener Neustadt, Wiener Neustadt, Austria. 27. Department of Affective Disorders, Q, Mood Disorders Research Unit, Aarhus University Hospital, Aarhus, Denmark. 28. Bipolar Disorder Research Program, Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil. 29. Mood Disorders Program, Fundacion San Vicente de Paul, Department of Psychiatry, Universidad de Antioquia, Medellín, Colombia. 30. Department of Psychiatry, University of Massachusetts, Worcester, MA, USA. 31. Michigan State University College of Human Medicine, Traverse City Campus, Traverse City, MI, USA. 32. Department of Neuroscience, NTNU, and St Olavs' University Hospital, Trondheim, Norway. 33. Department of Psychiatry, University of California San Diego, San Diego, CA, USA. 34. Deparment of Psychiatry, Diego Portales University, Santiago, Chile. 35. UCT/MRC Human Genetics Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 36. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe-University Frankfurt am Main, Germany. 37. Department of Psychiatry, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA. 38. Department of Neuroscience and Mental Health, Federal University of Bahia, Salvador, Brazil. 39. Department of Psychiatry, University of Cape Town, Cape Town, South Africa. 40. Bipolar Disorder Program, Neuroscience Institute, Favaloro University, Buenos Aires, Argentina. 41. Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 42. City of Helsinki, Department of Social Services and Health Care, Psychiatry, Helsinki, Finland. 43. Schizophrenia & Affective Disorders Research Project, Tokyo Metropolitan Institute of Medical Science, Seatagaya, Tokyo, Japan. 44. Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. 45. Department of Psychiatry, NIMHANS, Bangalore 560029, India. 46. Department of Psychology, Chapman University, Orange, CA, USA. 47. Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Abstract
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.
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.
Authors: Lakshmi N Yatham; Sidney H Kennedy; Sagar V Parikh; Ayal Schaffer; David J Bond; Benicio N Frey; Verinder Sharma; Benjamin I Goldstein; Soham Rej; Serge Beaulieu; Martin Alda; Glenda MacQueen; Roumen V Milev; Arun Ravindran; Claire O'Donovan; Diane McIntosh; Raymond W Lam; Gustavo Vazquez; Flavio Kapczinski; Roger S McIntyre; Jan Kozicky; Shigenobu Kanba; Beny Lafer; Trisha Suppes; Joseph R Calabrese; Eduard Vieta; Gin Malhi; Robert M Post; Michael Berk Journal: Bipolar Disord Date: 2018-03-14 Impact factor: 6.744
Authors: Ariadna Besga; Itxaso Gonzalez; Enrique Echeburua; Alexandre Savio; Borja Ayerdi; Darya Chyzhyk; Jose L M Madrigal; Juan C Leza; Manuel Graña; Ana Maria Gonzalez-Pinto Journal: Front Aging Neurosci Date: 2015-12-14 Impact factor: 5.750
Authors: Mirko Manchia; Giuseppe Maina; Bernardo Carpiniello; Federica Pinna; Luca Steardo; Virginia D'Ambrosio; Virginio Salvi; Martin Alda; Alfonso Tortorella; Umberto Albert Journal: Int J Bipolar Disord Date: 2017-08-21
Authors: Robert M Post; Lori L Altshuler; Ralph Kupka; Susan L McElroy; Mark A Frye; Heinz Grunze; Trisha Suppes; Paul E Keck; Willem A Nolen Journal: Int J Bipolar Disord Date: 2021-04-02