Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

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.

C Henry | Dan J Stein | B Etain | M Manchia | M Alda | F Bellivier | I. Melle | O. Andreassen | M. Frye | S. Strejilevich | Y. Osher | R. Belmaker | F. Bellivier | A. Fagiolini | E. Isometsä | G. MacQueen | S. Hassel | M. Zetin | M. Bauer | A. Pfennig | U. Lewitzka | T. Glenn | N. Rasgon | P. Whybrow | M. Berk | C. Henry | B. König | C. López-Jaramillo | E. Vieta | A. Reif | C. Baethge | G. Morken | E. Severus | M. Alda | R. Ramesar | L. Bossini | F. Kapczinski | B. Étain | H. Harima | B. Viswanath | A. Iacovides | S. Dodd | C. Simhandl | B. Lafer | J. Rybakowski | A. González-Pinto | E. Angelopoulos | S. Monteith | R. Bauer | M. Kunz | C. O’Donovan | M. Manchia | R. Ardau | S. Kliwicki | M. Del Zompo | F. Nery | E T Isometsä | O A Andreassen | Y. Bersudsky | P. Ritter | J. Conell | E. Cheung | E. Larsen | R. Muñoz | K. Sagduyu | K. Suominen | Y. Tatebayashi | Â. Scippa | B Lafer | M Bauer | D J Stein | E Vieta | R H Belmaker | K. Fountoulakis | P C Whybrow | I Melle | G MacQueen | A Reif | M A Frye | C Torrent | A Iacovides | K N Fountoulakis | A Pfennig | M Berk | S Dodd | C Simhandl | R Ramesar | M Del Zompo | M Zetin | Y Tatebayashi | F Kapczinski | C. Torrent | T Glenn | E Angelopoulos | R Ardau | C Baethge | R Bauer | T D Bjella | L Bossini | Y Bersudsky | E Y W Cheung | J Conell | A Fagiolini | J Garneau-Fournier | A Gonzalez-Pinto | H Harima | S Hassel | S Kliwicki | B König | R Krogh | M Kunz | E R Larsen | U Lewitzka | C Lopez-Jaramillo | W Marsh | M Martinez-Cengotitabengoa | S Monteith | G Morken | R Munoz | F G Nery | C O'Donovan | Y Osher | D Quiroz | N Rasgon | P Ritter | J K Rybakowski | K Sagduyu | A M Scippa | E Severus | S Strejilevich | A Hatim Sulaiman | K Suominen | H Tagata | B Viswanath | M J Wanchoo | T. Bjella | R. Krogh | W. Marsh | D. Quiroz | H. Tagata | J. Garneau-Fournier | M. Wanchoo | M. Martínez‐Cengotitabengoa | A. Hatim Sulaiman

[1]  R. A. Johnson,et al.  Initiation of use of alcohol, cigarettes, marijuana, cocaine, and other substances in US birth cohorts since 1919. , 1998, American journal of public health.

[2]  K Y Liang,et al.  Longitudinal data analysis for discrete and continuous outcomes. , 1986, Biometrics.

[3]  A. Nierenberg,et al.  Long-Term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD) , 2004, Biological Psychiatry.

[4]  Adrian E. Raftery,et al.  Normal Mixture Modelling for Model-Based Clustering,Classification, and Density Estimation , 2015 .

[5]  R. Baldessarini,et al.  Age at onset versus family history and clinical outcomes in 1,665 international bipolar‐I disorder patients , 2012, World psychiatry : official journal of the World Psychiatric Association.

[6]  F. Kapczinski,et al.  Birth‐cohort and dual diagnosis effects on age‐at‐onset in Brazilian patients with bipolar I disorder , 2009, Acta psychiatrica Scandinavica.

[7]  K. Kidd,et al.  Estimating age-of-onset distributions for disorders with variable onset. , 1980, American journal of human genetics.

[8]  M. Weissman,et al.  Birth-cohort changes in the rates of mania , 1990, Psychiatry Research.

[9]  Adrian E. Raftery,et al.  Model-Based Clustering, Discriminant Analysis, and Density Estimation , 2002 .

[10]  A. Karasz,et al.  Cultural differences in conceptual models of depression. , 2005, Social science & medicine.

[11]  M M Weissman,et al.  Increasing rates of depression. , 1989, JAMA.

[12]  Further evidence of relation between prenatal famine and major affective disorder. , 2000, The American journal of psychiatry.

[13]  G. Kirov,et al.  Age-at-onset in bipolar-I disorder: mixture analysis of 1369 cases identifies three distinct clinical sub-groups. , 2009, Journal of affective disorders.

[14]  P. Mitchell,et al.  Treatment of bipolar disorder , 1992, The Medical journal of Australia.

[15]  M. Rietschel,et al.  Age at onset in bipolar I affective disorder: further evidence for three subgroups. , 2003, The American journal of psychiatry.

[16]  James P. Smith,et al.  The Effects of World War II on Economic and Health Outcomes across Europe , 2012, Review of Economics and Statistics.

[17]  D. Kupfer,et al.  Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry. , 2003, The American journal of psychiatry.

[18]  Dan J Stein,et al.  Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study. , 2014, Journal of affective disorders.

[19]  D. Healy The Latest Mania: Selling Bipolar Disorder , 2006, PLoS medicine.

[20]  F. Thibaut,et al.  Evidence of a cohort effect for age at onset of schizophrenia. , 2001, The American journal of psychiatry.

[21]  G. Klerman,et al.  Are secular trends in major depression an artifact of recall? , 1991, Journal of psychiatric research.

[22]  I. Melle,et al.  Impact of sunlight on the age of onset of bipolar disorder , 2012, Bipolar disorders.

[23]  F. J. Díaz,et al.  Implicaciones clínicas de la edad de inicio del trastorno bipolar I: dos subgrupos con diferente pronóstico , 2009 .

[24]  J. Twenge The age of anxiety? Birth cohort change in anxiety and neuroticism, 1952-1993. , 2000, Journal of personality and social psychology.

[25]  P. Franke,et al.  Validity, reliability and objectivity of the family history method in psychiatry: A meta analysis , 2007, European Psychiatry.

[26]  P. Visscher,et al.  Genetic survival analysis of age-at-onset of bipolar disorder: evidence for anticipation or cohort effect in families , 2001, Psychiatric genetics.

[27]  H. Akiskal Validating 'hard' and 'soft' phenotypes within the bipolar spectrum: continuity or discontinuity? , 2003, Journal of affective disorders.

[28]  M. Alda,et al.  An admixture analysis of the age at index episodes in bipolar disorder , 2011, Psychiatry Research.

[29]  S. Faraone,et al.  Estimating age at onset distributions: The bias from prevalent cases and its impact on risk estimation , 1993, Genetic epidemiology.

[30]  P. Propping,et al.  Clinical evidence for genomic imprinting in bipolar I disorder , 1995, Acta psychiatrica Scandinavica.

[31]  V. Willour,et al.  Clinical correlates and familial aggregation of age at onset in bipolar disorder. , 2006, The American journal of psychiatry.

[32]  D. Kuh,et al.  Childhood influences on adult health: a review of recent work from the British 1946 national birth cohort study, the MRC National Survey of Health and Development. , 1997, Paediatric and perinatal epidemiology.

[33]  Bruce G. Link,et al.  Public conceptions of mental illness in 1950 and 1996: What is mental illness and is it to be feared? , 2000 .

[34]  P. Joyce,et al.  Birth cohort trends in major depression: increasing rates and earlier onset in New Zealand. , 1990, Journal of affective disorders.

[35]  M. Leboyer,et al.  Admixture analysis of age at onset in bipolar I affective disorder. , 2001, Archives of general psychiatry.

[36]  M. Schou,et al.  Lithium treatment at 52. , 2001, Journal of affective disorders.

[37]  R. Kessler,et al.  Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. , 1996, Archives of general psychiatry.

[38]  G. Carlson,et al.  Increased Rates of Bipolar Disorder Diagnoses Among U.S. Child, Adolescent, and Adult Inpatients, 1996–2004 , 2007, Biological Psychiatry.

[39]  R. C. Willets,et al.  The Cohort Effect: Insights and Explanations , 2004, British Actuarial Journal.

[40]  F. Bellivier,et al.  Characteristics and profiles of bipolar I patients according to age-at-onset: findings from an admixture analysis. , 2013, Journal of affective disorders.

[41]  D. Regier,et al.  Comparing age at onset of major depression and other psychiatric disorders by birth cohorts in five US community populations. , 1991, Archives of general psychiatry.

[42]  Adrian E. Raftery,et al.  How Many Clusters? Which Clustering Method? Answers Via Model-Based Cluster Analysis , 1998, Comput. J..

[43]  J. Nurnberger,et al.  Birth-cohort changes in manic and depressive disorders in relatives of bipolar and schizoaffective patients. , 1987, Archives of general psychiatry.

[44]  S. Strejilevich,et al.  Bipolar disorder in the elderly: a cohort study comparing older and younger patients , 2014, Acta psychiatrica Scandinavica.

[45]  M. Bauer,et al.  Psychological and endocrine abnormalities in refugees from East Germany: Part I. Prolonged stress, psychopathology, and hypothalamic-pituitary-thyroid axis activity , 1994, Psychiatry Research.

[46]  M. Manchia,et al.  Age at onset in Sardinian bipolar I patients: evidence for three subgroups. , 2008, Bipolar disorders.

[47]  M. Bauer,et al.  Psychological and endocrine abnormalities in refugees from East Germany: Part II. Serum levels of cortisol, prolactin, luteinizing hormone, follicle stimulating hormone, and testosterone , 1994, Psychiatry Research.

[48]  Ellen Frank,et al.  Demographic and clinical characteristics of individuals in a bipolar disorder case registry. , 2002, The Journal of clinical psychiatry.