A Comparison of Selected Risk Factors for Unipolar Depressive Disorder, Bipolar Affective Disorder, Schizoaffective Disorder, and Schizophrenia From a Danish Population-Based Cohort

Thomas Munk Laursen, M.Sc., Ph.D.; Trine Munk-Olsen, M.Sc.; Merete Nordentoft, M.P.H., Ph.D.; and Preben Bo Mortensen, D.M.Sc.

Objective: Growing evidence of an etiologic overlap between schizophrenia and bipolar disorder has become increasingly difficult to disregard. In this study, we examined paternal age, urbanicity of place of birth, being born "small for gestational age," and parental loss as risk factors for primarily schizophrenia and bipolar disorder, but also unipolar depressive disorder and schizoaffective disorder. Furthermore, we examined the incidence of the disorders in a population-based cohort and evaluated our results in the context of the Kraepelinian dichotomization.

Method: We established a register-based cohort study of more than 2 million persons born in Denmark between January 1, 1955, and July 1, 1987. Overall follow-up began on January 1, 1973 and ended on June 30, 2005. Relative risks for schizophrenia, bipolar disorder, unipolar depressive disorder, and schizoaffective disorder (ICD-8 or ICD-10) were estimated by survival analysis, using Poisson regression.

Results: Differences were found in age-specific incidences. Loss of a parent (especially by suicide) was a risk factor for all 4 disorders. High paternal age and urbanization at birth were risk factors for schizophrenia. Children born preterm had an excess risk of all disorders except schizophrenia if they were born "small for gestational age."

Conclusions: An overlap in the risk factors examined in this study was found, and the differences between the phenotypes were quantitative rather than qualitative, which suggests a genetic and environmental overlap between the disorders. However, large gender differences and differences in the age-specific incidences in the 4 disorders were present, favoring the Kraepelinian dichotomization.

(J Clin Psychiatry 2007;68:1673-1681)

Received Nov. 15, 2006; accepted Feb. 21, 2007. From the National Centre for Register-Based Research, University of Aarhus, Aarhus (Drs. Laursen and Mortensen and Ms. Munk-Olsen); and Bispebjerg Hospital, Department of Psychiatry, Copenhagen (Dr. Nordentoft), Denmark.

This study was supported by The Stanley Medical Research Institute. Dr. Laursen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. Psychiatric epidemiologic research at the National Centre for Register-Based Research is in part funded through a collaborative agreement with Centre for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Aarhus University Hospital, Risskov, Denmark.

The authors report no other financial affiliations relevant to the subject of this article.

Corresponding author and reprints: Thomas Munk Laursen, Ph.D., National Centre for Register-Based Research, University of Aarhus, Taasingegade 1, DK-8000 Aarhus C, Denmark (e-mail: tml@ncrr.dk).