BACKGROUND: Early-onset bipolar disorder has been associated with a significantly worse prognosis than late-onset BD and has been hypothesized to be a genetically homogenous subset of BD. A sizeable number of studies have investigated early-onset BD through linkage-analyses, candidate-gene association studies, genome-wide association studies (GWAS), and analyses of copy number variants (CNVs), but this literature has not yet been reviewed. METHODS: A systematic review was conducted using the PubMed database on articles published online before January 15, 2015 and after 1990. Separate searches were made for linkage studies, candidate gene-association studies, GWAS, and studies on CNVs. RESULTS: Seventy-three studies were included in our review. There is a lack of robust positive findings on the genetics of early-onset BD in any major molecular genetics method. LIMITATIONS: Early-onset populations were quite small in some studies. Variance in study methods hindered efforts to interpret results or conduct meta-analysis. CONCLUSIONS: The field is still at an early phase for research on early-onset BD. The largely null findings mirror the results of most genetics research on BD. Although most studies were underpowered, the null findings could mean that early-onset BD may not be as genetically homogenous as has been hypothesized or even that early-onset BD does not differ genetically from adult-onset BD. Nevertheless, clinically the probabilistic developmental risk trajectories associated with early-onset that may not be primarily genetically determined continued to warrant scrutiny. Future research should dramatically expand sample sizes, use atheoretical research methods like GWAS, and standardize methods.
BACKGROUND: Early-onset bipolar disorder has been associated with a significantly worse prognosis than late-onset BD and has been hypothesized to be a genetically homogenous subset of BD. A sizeable number of studies have investigated early-onset BD through linkage-analyses, candidate-gene association studies, genome-wide association studies (GWAS), and analyses of copy number variants (CNVs), but this literature has not yet been reviewed. METHODS: A systematic review was conducted using the PubMed database on articles published online before January 15, 2015 and after 1990. Separate searches were made for linkage studies, candidate gene-association studies, GWAS, and studies on CNVs. RESULTS: Seventy-three studies were included in our review. There is a lack of robust positive findings on the genetics of early-onset BD in any major molecular genetics method. LIMITATIONS: Early-onset populations were quite small in some studies. Variance in study methods hindered efforts to interpret results or conduct meta-analysis. CONCLUSIONS: The field is still at an early phase for research on early-onset BD. The largely null findings mirror the results of most genetics research on BD. Although most studies were underpowered, the null findings could mean that early-onset BD may not be as genetically homogenous as has been hypothesized or even that early-onset BD does not differ genetically from adult-onset BD. Nevertheless, clinically the probabilistic developmental risk trajectories associated with early-onset that may not be primarily genetically determined continued to warrant scrutiny. Future research should dramatically expand sample sizes, use atheoretical research methods like GWAS, and standardize methods.
Authors: Marie-Hélène Dizier; Bruno Etain; Mohamed Lajnef; Mark Lathrop; Detelina Grozeva; Nick Craddock; Chantal Henry; Sébastien Gard; Stéphane Jamain; Marion Leboyer; Frank Bellivier; Flavie Mathieu Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2012-05-24 Impact factor: 3.568
Authors: Anna Leszczyńska-Rodziewicz; Joanna Hauser; Monika Dmitrzak-Weglarz; Maria Skibińka; Piotr Czerski; Agnieszka Zakrzewska; Magdalena Kosmowska; Janusz K Rybakowski Journal: Med Sci Monit Date: 2005-05-25
Authors: Peter S Jensen; Mark A Frye; Joanna M Biernacka; Paul E Croarkin; Joan L Luby; Kelly Cercy; Jennifer R Geske; Marin Veldic; Matthew Simonson; Paramjit T Joshi; Karen Dineen Wagner; John T Walkup; Malik M Nassan; Alfredo B Cuellar-Barboza; Leah Casuto; Susan L McElroy Journal: J Clin Psychiatry Date: 2017 Nov/Dec Impact factor: 4.384
Authors: Janos L Kalman; Sergi Papiol; Andreas J Forstner; Urs Heilbronner; Franziska Degenhardt; Jana Strohmaier; Mazda Adli; Kristina Adorjan; Nirmala Akula; Martin Alda; Heike Anderson-Schmidt; Till Fm Andlauer; Ion-George Anghelescu; Raffaella Ardau; Bárbara Arias; Volker Arolt; Jean-Michel Aubry; Lena Backlund; Kim Bartholdi; Michael Bauer; Bernhard T Baune; Thomas Becker; Frank Bellivier; Antonio Benabarre; Susanne Bengesser; Abesh Kumar Bhattacharjee; Joanna M Biernacka; Armin Birner; Clara Brichant-Petitjean; Monika Budde; Pablo Cervantes; Caterina Chillotti; Sven Cichon; Scott R Clark; Francesc Colom; Ashley L Comes; Cristiana Cruceanu; Piotr M Czerski; Udo Dannlowski; Alexandre Dayer; Maria Del Zompo; Jay Raymond DePaulo; Detlef E Dietrich; Bruno Étain; Thomas Ethofer; Peter Falkai; Andreas Fallgatter; Christian Figge; Laura Flatau; Here Folkerts; Louise Frisen; Mark A Frye; Janice M Fullerton; Katrin Gade; Sébastien Gard; Julie S Garnham; Fernando S Goes; Maria Grigoroiu-Serbanescu; Anna Gryaznova; Maria Hake; Joanna Hauser; Stefan Herms; Per Hoffmann; Liping Hou; Markus Jäger; Stephane Jamain; Esther Jiménez; Georg Juckel; Jean-Pierre Kahn; Layla Kassem; John Kelsoe; Sarah Kittel-Schneider; Sebastian Kliwicki; Farah Klohn-Sagatholislam; Manfred Koller; Barbara König; Carsten Konrad; Nina Lackner; Gonzalo Laje; Mikael Landén; Fabian U Lang; Catharina Lavebratt; Marion Leboyer; Susan G Leckband; Mario Maj; Mirko Manchia; Lina Martinsson; Michael J McCarthy; Susan L McElroy; Francis J McMahon; Philip B Mitchell; Marina Mitjans; Francis M Mondimore; Palmiero Monteleone; Vanessa Nieratschker; Caroline M Nievergelt; Tomas Novák; Urban Ösby; Andrea Pfennig; James B Potash; Daniela Reich-Erkelenz; Andreas Reif; Jens Reimer; Eva Reininghaus; Markus Reitt; Stephan Ripke; Guy A Rouleau; Janusz K Rybakowski; Martin Schalling; Harald Scherk; Max Schmauß; Peter R Schofield; K Oliver Schubert; Eva C Schulte; Sybille Schulz; Fanny Senner; Giovanni Severino; Tatyana Shekhtman; Paul D Shilling; Christian Simhandl; Claire M Slaney; Carsten Spitzer; Alessio Squassina; Thomas Stamm; Sophia Stegmaier; Sebastian Stierl; Pavla Stopkova; Andreas Thiel; Sarah K Tighe; Alfonso Tortorella; Gustavo Turecki; Eduard Vieta; Julia Veeh; Martin von Hagen; Moritz E Wigand; Jens Wiltfang; Stephanie Witt; Adam Wright; Peter P Zandi; Jörg Zimmermann; Markus Nöthen; Marcella Rietschel; Thomas G Schulze Journal: Bipolar Disord Date: 2018-06-28 Impact factor: 6.744