Family history of psychiatric illness as a risk factor for Schizoaffective disorder - A Danish register-based cohort study

Background: Schizoaffective disorder may be related to both schizophrenia and bipolar disorders, but no population-based studies, to our knowledge, have investigated this association in families. Objectives: To determine whether a psychiatric history of schizoaffective disorder, bipolar disorder, or schizophrenia among parents and siblings is a risk factor for developing a schizoaffective disorder, and whether a specific pattern of family history of psychiatric illness exists in persons with schizoaffective disorder compared with persons with bipolar disorder or schizophrenia. Design: Register-based cohort study. Setting: Denmark. Cohort: The 2.4 million persons born in Denmark after 1952. Main Outcome Measures: Relative risks of the 3 illnesses estimated by Poisson regression. Results: In total, 1925 persons had a schizoaffective disorder, 3721 had a bipolar disorder, and 12 501 had schizophrenia. The relative risk of schizoaffective disorder was 2.76 (95% confidence interval, 2.49-3.06) if a first-degree relative had a history of mental illness compared with a person with no first-degree relatives with such a history. There was an additional risk (95% confidence interval) of 2.57 (2.11-3.13), 3.23 (2.63-3.95), or 1.92 (1.43-2.57) if the first-degree relative had schizophrenia, bipolar disorder, or schizoaffective disorder, respectively, compared with other psychiatric admissions. When bipolar disorder was the outcome, bipolar disorder in first-degree relatives was by far the significantly strongest risk factor. When schizophrenia was the outcome, the significantly strongest risk factor was schizophrenia among first-degree relatives. Conclusion: Schizoaffective disorder is not simply a subgroup of either bipolar disorder or schizophrenia but may be genetically linked to both, with schizoaffective disorder being a subtype of each or a genetic intermediate form.