Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue Research Square - Preprint Année : 2023

Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder

Marisol Herrera-Rivero (1) , Karina Gutiérrez-Fragoso (2) , Anbupalam Thalamuthu (3) , Azmeraw Amare (4) , Mazda Adli (5) , Kazufumi Akiyama (6) , Nirmala Akula (7) , Raffaella Ardau (8) , Bárbara Arias (9, 10) , Jean-Michel Aubry (11) , Lena Backlund (12) , Frank Bellivier (13) , Antonio Benabarre (9) , Susanne Bengesser (14) , Bhattacharjee Abesh (15) , Joanna Biernacka (16) , Armin Birner (14) , Micah Cearns (4) , Pablo Cervantes (17) , Hsi-Chung Chen (18) , Caterina Chillotti (8) , Sven Cichon (16) , Scott Clark (4) , Francesc Colom (19) , Cristiana Cruceanu (20) , Piotr Czerski (21) , Nina Dalkner (14) , Franziska Degenhardt (22) , Maria Del Zompo (8) , J Raymond Depaulo (23) , Bruno Etain (24, 25, 26, 27) , Peter Falkai (28) , Ewa Ferensztajn-Rochowiak (21) , Andreas Forstner (22) , Josef Frank (29) , Louise Frisen (30) , Mark Frye (16) , Janice Fullerton (31) , Carla Gallo (32) , Sebastien Gard (33) , Julie Garnham (34) , Fernando Goes (23) , Maria Grigoroiu-Serbanescu (35) , Paul Grof (36) , Ryota Hashimoto (37) , Roland Hasler (38) , Joanna Hauser (21) , Urs Heilbronner (39) , Stefan Herms (40) , Per Hoffmann (41) , Liping Hou (7) , Yihsiang Hsu (16) , Stéphane Jamain (42) , Esther Jiménez (9, 43, 10) , Jean-Pierre Kahn (44) , Layla Kassem (30) , Tadafumi Kato (45) , John Kelsoe (46) , Sarah Kittel-Schneider (47) , Po-Hsiu Kuo (48) , Joachim Kurtz (49) , Ichiro Kusumi (50) , Barbara König (51) , Gonzalo Laje (52) , Mikael Landén (53) , Catharina Lavebratt (12) , Marion Leboyer (54) , Susan Leckband (55) , Mario Maj (56) , Mirko Manchia (57) , Cynthia Marie-Claire (24) , Lina Martinsson (12) , Michael Mccarthy (58) , Susan Mcelroy (59) , Vincent Millischer (60) , Marina Mitjans (61) , Francis Mondimore (31) , Palmiero Monteleone (62, 56) , Caroline Nievergelt (46) , Tomas Novak (63) , Markus Nöthen (30) , Claire Odonovan (64) , Norio Ozaki (65) , Sergi Papiol (28) , Andrea Pfennig (66) , Claudia Pisanu (8) , James Potash (67) , Andreas Reif (68) , Eva Reininghaus (14) , Hélène Richard-Lepouriel (11) , Gloria Roberts (69) , Guy Rouleau (70) , Janusz Rybakowski (21) , Martin Schalling (12) , Peter Schofield (31) , Klaus Oliver Schubert (4) , Eva Schulte (28) , Barbara Schweizer (71) , Giovanni Severino (8) , Tatyana Shekhtman (46) , Paul Shilling (46) , Kazutaka Shimoda (6) , Christian Simhandl (72) , Claire Slaney (57) , Alessio Squassina (8) , Thomas Stamm (5) , Pavla Stopkova (73) , Fabian Streit (74) , Fasil Ayele (75) , Alfonso Tortorella (75) , Gustavo Turecki (70) , Julia Veeh (68) , Eduard Vieta (76) , Biju Viswanath (77) , Stephanie Witt (78) , Peter Zandi (23) , Martin Alda (57) , Michael Bauer (66) , Francis Mcmahon (79) , Philip Mitchell (80) , Marcella Rietschel (81) , Thomas Schulze (28) , Bernhard Baune (1)
1 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
2 ITSOEH - Instituto Tecnológico Superior del Oriente del Estado de Hidalgo [Apan, HGO, Mexique]
3 University of New South Wales [Kensington]
4 University of Adelaide
5 Charité - UniversitätsMedizin = Berlin University Medicine
6 Dokkyo Medical University
7 NIH - National Institutes of Health [Bethesda, MD, USA]
8 UniCa - Università degli Studi di Cagliari = University of Cagliari = Université de Cagliari
9 UB - Universitat de Barcelona
10 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]
11 HUG - Hôpitaux universitaires de Genève = University Hospitals of Geneva
12 Karolinska Institutet [Stockholm]
13 Institut Montaigne
14 Medical University of Graz = Medizinische Universität Graz
15 JMDVAMC - Jennifer Moreno Department of Veterans Affairs Medical Center [San Diego, CA, USA]
16 Mayo Clinic
17 MUHC - McGill University Health Center [Montreal]
18 NTUH - National Taiwan University Hospital [Taipei]
19 IMIM-Hospital del Mar
20 Max-Planck-Institut für Psychiatrie
21 PUMS - Poznan University of Medical Sciences [Poland]
22 Universität Bonn = University of Bonn
23 JHU - Johns Hopkins University
24 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
25 HUSLS-LRB-FW - Département de Psychiatrie et de Médecine Addictologique [AP-HP HU Saint-Louis, Lariboisière, Fernand Widal]
26 GHU AP-HP Nord - Université Paris Cité
27 Fondation FondaMental [Créteil]
28 University-Hospital Munich-Großhadern [München]
29 Central Institute of Mental Health [Mannheim]
30 University Hospital Bonn
31 NeuRA - Neuroscience Research Australia
32 UPCH - Universidad Peruana Cayetano Heredia
33 Centre hospitalier Charles Perrens [Bordeaux]
34 CDHA - Capital District Health Authority [Nova Scotia, Canada]
35 ERA-LEARN - Prof. Dr. Alexandru Obregia Psychiatry Hospital
36 Centre de toxicomanie et de santé mentale [Toronto, ON, Canada]
37 Kyoto University
38 HUG - Hôpitaux Universitaires de Genève
39 IPPG - Institute of Psychiatric Phenomics and Genomics
40 Unibas - Université de Bâle = University of Basel = Basel Universität
41 Institute of Human Genetics
42 IMRB - Institut Mondor de Recherche Biomédicale
43 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
44 IPSE - Laboratoire IPSé - Psychopathologie de l'identité, de la pensée et du processus de santé
45 RIKEN CBS - RIKEN Center for Brain Science [Wako]
46 UC San Diego - University of California [San Diego]
47 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg [Würsburg, Germany]
48 NTU - National Taiwan University [Taiwan]
49 Universität Heidelberg [Heidelberg] = Heidelberg University
50 Hokkaido University [Sapporo, Japan]
51 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
52 Columbia University [New York]
53 GU - Göteborgs Universitet = University of Gothenburg
54 FHU ADAPT - Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie = Addiction And Psychiatry Transformation with Precision Medicine [Créteil, France]
55 VASDHS - VA San Diego Healthcare System [San Diego, CA, USA]
56 UniOr - Università di Napoli L'Orientale = University of Naples
57 Dalhousie University [Halifax]
58 University of Pennsylvania
59 UC - University of Cincinnati
60 Department of Laboratory Medicine [Karolinska Institutet]
61 MPI - Max Planck Institute of Experimental Medicine [Göttingen]
62 UNISA - Università degli Studi di Salerno = University of Salerno
63 NIMH - National Institute of Mental Health [Klecany, Czech Republic]
64 UCC - University College Cork
65 Nagoya University
66 University Hospital Carl Gustav Carus [Dresden, Germany]
67 Johns Hopkins University School of Medicine [Baltimore]
68 Frankfurt University Hospital
69 USC - University of Southern California
70 McGill University = Université McGill [Montréal, Canada]
71 IM - LK - Innere Medizin - Luzerner Kantonsspital [Luzern, Suisse]
72 Medizinische Universität Wien = Medical University of Vienna
73 First Faculty of Medicine Charles University
74 University of Heidelberg, Medical Faculty
75 UNIPG - Università degli Studi di Perugia = University of Perugia
76 HCB - Hospital Clínico de Barcelona [Spain]
77 NIMHANS - National Institute Of Mental Health & Neuro Sciences [Bengaluru, Karnataka, Inde]
78 University Hospital Mannheim | Universitätsmedizin Mannheim
79 NIMH - National Institute of Mental Health
80 UNSW - University of New South Wales [Sydney]
81 Hochschule Mannheim - University of Applied Sciences
Azmeraw Amare
Joanna Biernacka
Micah Cearns
Sven Cichon
  • Fonction : Auteur
Scott Clark
Mark Frye
Janice Fullerton
Ryota Hashimoto
Yihsiang Hsu
  • Fonction : Auteur
John Kelsoe
Po-Hsiu Kuo
Ichiro Kusumi
Catharina Lavebratt
Markus Nöthen
Norio Ozaki
Andreas Reif
Martin Schalling
Peter Schofield
Klaus Oliver Schubert
Kazutaka Shimoda
Eduard Vieta
Martin Alda
Francis Mcmahon
Philip Mitchell

Résumé

Abstract The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi + Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1x10 − 4 values, including HAS3 , CNTNAP5 and NFIB . Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP’s age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4 , XKR4 , NRXN1 , NRG1/3 and GRK5 . Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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Dates et versions

inserm-04198049 , version 1 (06-09-2023)

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Marisol Herrera-Rivero, Karina Gutiérrez-Fragoso, Anbupalam Thalamuthu, Azmeraw Amare, Mazda Adli, et al.. Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder. Research Square - Preprint, 2023, pp.rs.3.rs-3068352. ⟨10.21203/rs.3.rs-3068352/v1⟩. ⟨inserm-04198049⟩
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