Bipolar Disorder, Schizoaffective Disorder, and Schizophrenia Overlap: A New Comorbidity Index

National Centre for Register-Based Research, University of Aarhus, Taasingegade 1, DK-8000 Aarhus C, Denmark.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 07/2009; 70(10):1432-8. DOI: 10.4088/JCP.08m04807
Source: PubMed


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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    • "e l s e v i e r . c o m / l o c a t e / y n i m g that SAD represents the co-occurrence of SZ and BP (Laursen et al., 2009) or an atypical form of SZ/BP (Bogan et al., 2000; Cascade et al., 2009; Lake and Hurwitz, 2006). SAD is also discussed as a heterogeneous group, which consists of both SZ and BP (Levitt and Tsuang, 1988). "
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    ABSTRACT: Schizophrenia (SZ), bipolar disorder (BP) and schizoaffective disorder (SAD) share some common symptoms, and there is a debate about whether SAD is an independent category. To the best of our knowledge, no study has been done to differentiate these three disorders or to investigate the distinction of SAD as an independent category using fMRI data. The present study is aimed to explore biomarkers from resting-state fMRI networks for differentiating these disorders and investigate the relationship among these disorders based on fMRI networks with an emphasis on SAD. Firstly, a novel group ICA method, group information guided independent component analysis (GIG-ICA), was applied to extract subject-specific brain networks from fMRI data of 20 healthy controls (HC), 20 SZ patients, 20 BP patients, 20 patients suffering SAD with manic episodes (SADM), and 13 patients suffering SAD with depressive episodes exclusively (SADD). Then, five-level one-way analysis of covariance and multiclass support vector machine recursive feature elimination were employed to identify discriminative regions from the networks. Subsequently, the t-distributed stochastic neighbor embedding (t-SNE) projection and the hierarchical clustering methods were implemented to investigate the relationship among those groups. Finally, to evaluate the generalization ability, 16 new subjects were classified based on the found regions and the trained model using original 93 subjects. Results show that the discriminative regions mainly include frontal, parietal, precuneus, cingulate, supplementary motor, cerebellar, insula and supramarginal cortices, which performed well in distinguishing different groups. SADM and SADD were the most similar to each other, although SADD had greater similarity to SZ compared to other groups, which indicates SAD may be an independent category. BP was closer to HC compared with other psychotic disorders. In summary, resting-state fMRI brain networks extracted via GIG-ICA provide a promising potential to differentiate SZ, BP, and SAD. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 07/2015; 122. DOI:10.1016/j.neuroimage.2015.07.054 · 6.36 Impact Factor
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    • "Neuropsychiatric disorders, including Autism Spectrum Disorders (ASDs), Bipolar Disorder (BD), and Schizophrenia (SCZ) have been known for a long time to be influenced by genetic risk factors without following Mendelian patterns of heritability. They are often co-morbid with each other or with other conditions, such as intellectual disability.41-43 Rather than being caused by a few highly penetrant mutations, neuropsychiatric disorders appear to be associated with subtle defects in numerous genes, each conferring a small increase in disease risk. "
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    ABSTRACT: Clathrin-mediated endocytosis is one of several mechanisms for retrieving transmembrane proteins from the cell surface. This key mechanism is highly conserved in evolution and is found in any eukaryotic cell from yeast to mammals. Studies from several model organisms have revealed that filamentous actin (F-actin) plays multiple distinct roles in shaping Clathrin-mediated endocytosis. Yet, despite the identification of numerous molecules at the interface between endocytic machinery and the cytoskeleton, our mechanistic understanding of how F-actin regulates endocytosis remains limited. Key insights come from neurons where vesicular release and internalization are critical to pre- and postsynaptic function. Recent evidence from human genetics puts postsynaptic organization, glutamate receptor trafficking, and F-actin remodeling in the spotlight as candidate mechanisms underlying neuropsychiatric disorders. Here I review recent findings that connect the F-actin cytoskeleton mechanistically to Clathrin-mediated endocytosis in the central nervous system, and discuss their potential involvement in conferring risk for neuropsychiatric disorder.
    Communicative & integrative biology 04/2014; 7(3):e28740. DOI:10.4161/cib.28740
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    • "One possibility is that elevated thought problems are indicative of psychotic processes. Some researchers propose possible overlaps as well as common risk factors between schizophrenia and BD (Djurovic et al., 2010; Laursen, Agerbo, & Pedersen, 2009; Murray et al., 2004). Building on genetic linkage studies (perhaps particularly bipolar I disorder; Kelsoe, 2003), BD is thought to share certain susceptibility genes with schizoaffective disorder and schizophrenia, and may therefore fall within the spectrum of psychotic disorders. "
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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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