Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families
Abstract The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large sam...
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Format: | Article |
Language: | English |
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Nature Publishing Group
2021-01-01
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Series: | Translational Psychiatry |
Online Access: | https://doi.org/10.1038/s41398-020-01146-0 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jose Guzman-Parra Fabian Streit Andreas J. Forstner Jana Strohmaier Maria José González Susana Gil Flores Francisco J. Cabaleiro Fabeiro Francisco del Río Noriega Fermin Perez Perez Jesus Haro González Guillermo Orozco Diaz Yolanda de Diego-Otero Berta Moreno-Kustner Georg Auburger Franziska Degenhardt Stefanie Heilmann-Heimbach Stefan Herms Per Hoffmann Josef Frank Jerome C. Foo Lea Sirignano Stephanie H. Witt Sven Cichon Fabio Rivas Fermín Mayoral Markus M. Nöthen Till F. M. Andlauer Marcella Rietschel |
spellingShingle |
Jose Guzman-Parra Fabian Streit Andreas J. Forstner Jana Strohmaier Maria José González Susana Gil Flores Francisco J. Cabaleiro Fabeiro Francisco del Río Noriega Fermin Perez Perez Jesus Haro González Guillermo Orozco Diaz Yolanda de Diego-Otero Berta Moreno-Kustner Georg Auburger Franziska Degenhardt Stefanie Heilmann-Heimbach Stefan Herms Per Hoffmann Josef Frank Jerome C. Foo Lea Sirignano Stephanie H. Witt Sven Cichon Fabio Rivas Fermín Mayoral Markus M. Nöthen Till F. M. Andlauer Marcella Rietschel Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families Translational Psychiatry |
author_facet |
Jose Guzman-Parra Fabian Streit Andreas J. Forstner Jana Strohmaier Maria José González Susana Gil Flores Francisco J. Cabaleiro Fabeiro Francisco del Río Noriega Fermin Perez Perez Jesus Haro González Guillermo Orozco Diaz Yolanda de Diego-Otero Berta Moreno-Kustner Georg Auburger Franziska Degenhardt Stefanie Heilmann-Heimbach Stefan Herms Per Hoffmann Josef Frank Jerome C. Foo Lea Sirignano Stephanie H. Witt Sven Cichon Fabio Rivas Fermín Mayoral Markus M. Nöthen Till F. M. Andlauer Marcella Rietschel |
author_sort |
Jose Guzman-Parra |
title |
Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families |
title_short |
Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families |
title_full |
Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families |
title_fullStr |
Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families |
title_full_unstemmed |
Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families |
title_sort |
clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families |
publisher |
Nature Publishing Group |
series |
Translational Psychiatry |
issn |
2158-3188 |
publishDate |
2021-01-01 |
description |
Abstract The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development. |
url |
https://doi.org/10.1038/s41398-020-01146-0 |
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doaj-bbfe0516372846358808b84f40df16282021-01-17T12:57:38ZengNature Publishing GroupTranslational Psychiatry2158-31882021-01-0111111010.1038/s41398-020-01146-0Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex familiesJose Guzman-Parra0Fabian Streit1Andreas J. Forstner2Jana Strohmaier3Maria José González4Susana Gil Flores5Francisco J. Cabaleiro Fabeiro6Francisco del Río Noriega7Fermin Perez Perez8Jesus Haro González9Guillermo Orozco Diaz10Yolanda de Diego-Otero11Berta Moreno-Kustner12Georg Auburger13Franziska Degenhardt14Stefanie Heilmann-Heimbach15Stefan Herms16Per Hoffmann17Josef Frank18Jerome C. Foo19Lea Sirignano20Stephanie H. Witt21Sven Cichon22Fabio Rivas23Fermín Mayoral24Markus M. Nöthen25Till F. M. Andlauer26Marcella Rietschel27Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA)Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityCentre for Human Genetics, University of MarburgDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Mental Health, Hospital of Puerto RealDepartment of Mental Health, University Hospital of Reina SofiaDepartment of Mental Health, Hospital of JaenDepartment of Mental Health, Hospital of Jerez de la FronteraDepartment of Mental Health, Hospital of Puerto RealDepartment of Mental Health, Hospital Punta de EuropaUnidad de Gestión Clínica del Dispositivo de Cuidados Críticos y Urgencias del Distrito Sanitario Málaga-Coin-GuadalhorceDepartment of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA)Department of Personality, Assessment and Psychological Treatment, University of Malaga, Institute of Biomedicine of Málaga (IBIMA)Department of Neurology, Goethe University Medical SchoolInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Biomedicine, University of BaselDepartment of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA)Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA)Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnDepartment of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of MunichDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityAbstract The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development.https://doi.org/10.1038/s41398-020-01146-0 |