Bipolar Disorder, Schizoaffective Disorder, and Schizophrenia Overlap: A New Comorbidity Index
ABSTRACT Growing evidence of an etiologic overlap between schizophrenia, schizoaffective disorder, and bipolar disorder has become increasingly difficult to disregard. We investigated the magnitude of the overlap between the clinical diagnoses of bipolar affective disorder, schizoaffective disorder, and schizophrenia over a 35-year period based on the entire Danish population.
We established a register-based prospective cohort study of more than 2.5 million persons born in Denmark after 1954. Risks for the 3 psychiatric disorders were estimated by survival analysis using the Aalen-Johansen method. Cohort members were followed from 1970 to 2006. We introduced a new comorbidity index measuring the magnitude of the overlap between the 3 disorders.
Overall, 12,734 patients were admitted with schizophrenia, 4,205 with bipolar disorder, and 1,881 with schizoaffective disorder. A female bipolar patient's risk of also being admitted with a schizoaffective disorder by the age of 45 years was approximately 103 times higher than that of a woman at the same age in the general population. Thus, we defined the comorbidity index between schizoaffective disorder and bipolar disorder at age 45 years to be 103. At age 45 years, the index between schizophrenia and schizoaffective disorder was 80 and between schizophrenia and bipolar disorder was 20. Similar large comorbidity indexes were found for men.
A large comorbidity index between schizophrenia and schizoaffective disorder was found, as well as a large index between bipolar disorder and schizoaffective disorder. But, more surprisingly, it was clear that a substantial comorbidity index between bipolar disorder and schizophrenia was present. This study supports the existence of an overlap between bipolar disorder and schizophrenia and thus challenges the strict categorical approach used in both DSM-IV and ICD-10 classification systems.
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ABSTRACT: There is growing evidence that many offspring of parents with bipolar disorder (BD) will develop moderate to severe forms of psychopathology during childhood and adolescence, including thought problems. The purpose of this study was to evaluate the developmental progression of thought problems within the context of a family risk study. Repeated assessments of thought problems, spanning approximately 15 years, were conducted in offspring (N = 192 from 98 families) of parents diagnosed with BD (O-BD), unipolar depression (O-UNI), or no significant psychiatric or medical problems (O-WELL). Survival analysis showed that the O-BD group had the greatest estimated probability of developing thought problems over time, followed by O-UNI, and then O-WELL and O-BD exhibiting higher levels of persistence than O-WELL. Parent-reported thought problems in childhood and adolescence predicted a range of problems in young adulthood. Disturbances in reality testing and other atypical behaviors are likely to disrupt progression through important developmental periods and to associate with poor outcomes. These findings are likely relevant to preventing the occurrence or progression of problems in offspring of bipolar parents. The study of thought problems across development represents an important area of continued research in children at risk for development of affective disorders.Development and Psychopathology 11/2013; 25(4pt1):1079-1091. DOI:10.1017/S0954579413000382 · 4.89 Impact Factor
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ABSTRACT: Over the past century, the definition and classification of psychiatric disorders has evolved through a combination of historical trends, clinical observations, and empirical research. The current nosology, instantiated in the DSM-5 and ICD-10, rests on descriptive criteria agreed upon by a consensus of experts. While the development of explicit criteria has enhanced the reliability of diagnosis, the validity of the current diagnostic categories has been the subject of debate and controversy. Genetic studies have long been regarded as a key resource for validating the boundaries among diagnostic categories. Genetic epidemiologic studies have documented the familiality and heritability of clinically defined psychiatric disorders and molecular genetic studies have begun to identify specific susceptibility variants. At the same time, there is growing evidence from family, twin and genomic studies that genetic influences on psychiatric disorders transcend clinical boundaries. Here I review this evidence for cross-disorder genetic effects and discuss the implications of these findings for psychiatric nosology. Psychiatric genetic research can inform a bottom-up reappraisal of psychopathology that may help the field move beyond a purely descriptive classification and toward an etiology-based nosology. © 2013 Wiley Periodicals, Inc.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2013; 162(7):559-78. DOI:10.1002/ajmg.b.32174 · 3.27 Impact Factor
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ABSTRACT: Epidemiological studies indicate that having any family member with schizophrenia increases the risk of schizophrenia in the probands. However, genome-wide association studies (GWAS) have accounted for little of this variation. The aim of this study was to use a population-based sample to explore the influence of single-nucleotide polymorphisms (SNPs) on the excess schizophrenia risk in offspring of parents with a psychotic, bipolar affective or other psychiatric disorder. A nested case-control study with 739 cases with schizophrenia and 800 controls. Their parents and siblings. Information from national health registers and GWAS data from the national neonatal biobank. Offspring schizophrenia risk was elevated in those whose mother, father or siblings had been diagnosed with schizophrenia or related psychosis, bipolar affective disorder or any other psychiatric disorder. The rate ratio was 9.31 (3.85; 22.44) in offspring whose 1st degree relative was diagnosed with schizophrenia. This rate ranged between 8.31 and 11.34 when adjusted for each SNP individually and shrank to 8.23 (3.13; 21.64) when adjusted for 25% of the SNP-variation in candidate genes. The percentage of the excess risk associated with a family history of schizophrenia mediated through genome-wide SNP-variation ranged between -6.1%(-17.0%;2.6%) and 4.1%(-3.9%;15.2%). Analogous results were seen for each parent and for histories of bipolar affective and other psychiatric diagnoses. The excess risk of schizophrenia in offspring of parents who have a psychotic, bipolar affective or other psychiatric disorder is not currently explained by the SNP variation included in this study in accordance with findings from published genetic studies.Schizophrenia Research 11/2011; 134(2-3):246-52. DOI:10.1016/j.schres.2011.10.025 · 4.43 Impact Factor