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1. The Patient-Reported Experience Measure for Improving qUality of care in Mental health (PREMIUM) project in France: study protocol for the development and implementation strategy

Author

Fernandes S, Fond G, Zendjidjian X, Michel P, Baumstarck K, Lancon C, Berna F, Schurhoff F, Aouizerate B, Henry C, Etain B, Samalin L, Leboyer M, Llorca PM, Coldefy M, Auquier P, and Boyer L

Subjects
patient reported experience measures, quality of care, item bank, computerized adaptive testing, psychiatry, Medicine (General), R5-920
Abstract

Sara Fernandes,1 Guillaume Fond,1 Xavier Zendjidjian,1 Pierre Michel,1 Karine Baumstarck,1 Christophe Lancon,1 Fabrice Berna,2 Franck Schurhoff,2 Bruno Aouizerate,2 Chantal Henry,2 Bruno Etain,2 Ludovic Samalin,2 Marion Leboyer,2 Pierre-Michel Llorca,2 Magali Coldefy,3 Pascal Auquier,1 Laurent Boyer1 On behalf of the French PREMIUM Group 1Aix-Marseille University, School of Medicine, CEReSS – Health Service Research and Quality of Life Center – EA 3279 Research Unit, Marseille, France; 2FondaMental Foundation, Créteil, France; 3Institute for Research and Information in Health Economics (IRDES), Paris, France Background: Measuring the quality and performance of health care is a major challenge in improving the efficiency of a health system. Patient experience is one important measure of the quality of health care, and the use of patient-reported experience measures (PREMs) is recommended. The aims of this project are 1) to develop item banks of PREMs that assess the quality of health care for adult patients with psychiatric disorders (schizophrenia, bipolar disorder, and depression) and to validate computerized adaptive testing (CAT) to support the routine use of PREMs; and 2) to analyze the implementation and acceptability of the CAT among patients, professionals, and health authorities.Methods: This multicenter and cross-sectional study is based on a mixed method approach, integrating qualitative and quantitative methodologies in two main phases: 1) item bank and CAT development based on a standardized procedure, including conceptual work and definition of the domain mapping, item selection, calibration of the item bank and CAT simulations to elaborate the administration algorithm, and CAT validation; and 2) a qualitative study exploring the implementation and acceptability of the CAT among patients, professionals, and health authorities.Discussion: The development of a set of PREMs on quality of care in mental health that overcomes the limitations of previous works (ie, allowing national comparisons regardless of the characteristics of patients and care and based on modern testing using item banks and CAT) could help health care professionals and health system policymakers to identify strategies to improve the quality and efficiency of mental health care.Trial registration: NCT02491866. Keywords: patient-reported experience measures, quality of care, item bank, computerized adaptive testing, psychiatry

Published
2019

2. Association between the PPP3CC gene, coding for the calcineurin gamma catalytic subunit, and bipolar disorder

Author

Bellivier Frank, Chevalier Fabien, El Khoury Marie-Anne, Etain Bruno, Miot Stéphanie, Mathieu Flavie, Leboyer Marion, Giros Bruno, and Tzavara Eleni T

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Calcineurin is a neuron-enriched phosphatase that regulates synaptic plasticity and neuronal adaptation. Activation of calcineurin, overall, antagonizes the effects of the cyclic AMP activated protein/kinase A. Thus, kinase/phosphatase dynamic balance seems to be critical for transition to long-term cellular responses in neurons, and disruption of this equilibrium should induce behavioral impairments in animal models. Genetic animal models, as well as post-mortem studies in humans have implicated calcineurin dependent calcium and cyclic AMP regulated phosphorylation/dephosphorylation in both affective responses and psychosis. Recently, genetic association between schizophrenia and genetic variation of the human calcineurin A gamma subunit gene (PPP3CC) has been reported. Methods Based on the assumption of the common underlying genetic factor in schizophrenia and bipolar affective disorder (BPAD), we performed association analysis of CC33 and CCS3 polymorphisms of the PPP3CC gene reported to be associated with schizophrenia in a French sample of 115 BPAD patients and 97 healthy controls. Results Carrying 'CT' or 'TT' genotypes of the PPP3CC-CC33 polymorphism increased risk to develop BPAD comparing to carry 'CC' genotype (OR = 1.8 [1.01–3.0]; p = 0.05). For the PPP3CC-CCS3 polymorphism, 'AG' or 'GG' carriers have an increased risk to develop BPAD than 'AA' carriers (OR = 2.8 [1.5–5.2]). The CC33 and CCS3 polymorphisms were observed in significant linkage disequilibrium (D' = 0.91, r2 = 0.72). Haplotype frequencies were significantly different in BPAD patients than in controls (p = 0.03), with a significant over-transmission of the 'TG' haplotype in BPAD patients (p = 0.001). Conclusion: We suggest that the PPP3CC gene might be a susceptibility gene for BPAD, in accordance with current neurobiological hypotheses that implicate dysregulation of signal-transduction pathways, such as those regulated by calcineurin, in the etiology of affective disorders.

Published
2008
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3. Diet quality and associations with lactate and metabolic syndrome in bipolar disorder

Author

Etain, B., Olié, E., Leboyer, M., Haffen, E., Llorca, P.M., Barteau, V., Bensalem, S., Godin, O., Laouamri, H., Souryis, K., Hotier, S., Pelletier, A., Hergeta, F., Petrucci, J., Willaume, L., Bellivier, F., Hennion, V., Marlinge, E., Meheust, J., Richard, A., Carminati, M., Francisque, H., Dubertret, C., Mazer, N., Portalier, C., Scognamiglio, C., Bing, A., Laurent, P., Gard, S., M'Bailara, K., Elkael, C., Hoorelbeke, F., Minois, I., Sportich, J., Da Ros, N., Boukhobza, L., Courtet, P., Denat, S., Deffinis, B., Ducasse, D., Gachet, M., Lengvenyté, A., Molière, F., Nass, L., Tarquini, G., Lefrere, A., Moreau, E., Pastol, J., Groppi, F., Polomeni, H., Bauberg, J., Lescalier, L., Muraccioli, I., Suray, A., Cohen, R., Kahn, J.P., Milazzo, M., Wajsbrot-Elgrabli, O., Bougerol, T., Pouchon, A., Bertrand, A., Fredembach, B., Suisse, A., Denoual, Q., Polosan, M., Galliot, A.M., Brehon, L., Bonny, G., Durand, L., Feuga, V., Kayser, N., Roux, P., Aubin, V., Cussac, I., Dupont, M.A., Loftus, J., Medecin, I., Samalin, L., Mennetrier, M., Bonnet, T., Lacelle, D., Vayssié, M., Beal, C., Blanc, O., Zachos, Kassandra A., Godin, Ophelia, Choi, Jaehyoung, Jung, Jae H., Aouizerate, Bruno, Aubin, Valérie, Bellivier, Frank, Belzeaux-R, Raoul, Courtet, Philippe, Dubertret, Caroline, Etain, Bruno, Haffen, Emmanuel, Lefrere A, Antoine, Llorca, Pierre-Michel, Olié, Emilie, Polosan, Mircea, Samalin, Ludovic, Schwan, Raymund, Roux, Paul, Barau, Caroline, Richard, Jean Romain, Tamouza, Ryad, Leboyer, Marion, and Andreazza, Ana C.

Published
2024
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4. Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

Author

Etain, B., Olié, E., Leboyer, M., Haffen, E., Llorca, PM, Barteau, V., Bensalem, S., Godin, O., Laouamri, H., Souryis, K., Hotier, S., Pelletier, A., Hergeta, F., Petrucci, J., Willaume, L., Bellivier, F., Hennion, V., Marlinge, E., Meheust, J., Richard, A., Carminati, M., Francisque, H., Dubertret, C., Mazer, N., Portalier, C., Scognamiglio, C., Bing, A., Laurent, P., Gard, S., M'Bailara, K., Elkael, C., Hoorelbeke, F., Minois, I., Sportich, J., Da Ros, N., Boukhobza, L., Courtet, P., Denat, S., Deffinis, B., Ducasse, D., Gachet, M., Lengvenyté, A., Molière, F., Nass, L., Tarquini, G., Lefrere, A., Moreau, E., Pastol, J., Groppi, F., Polomeni, H., Bauberg, J, Lescalier, L., Muraccioli, I., Suray, A., Cohen, R., Kahn, J.P., Milazzo, M., Wajsbrot-Elgrabli, O., Bougerol, T., Pouchon, A., Bertrand, A, Fredembach, B., Suisse, A., Denoual, Q, Polosan, M, Galliot, A.M., Brehon, L., Bonny, G, Durand, L, Feuga, V, Kayser, N., Roux, P., Aubin, V., Cussac, I., Dupont, M.A, Loftus, J., Medecin, I., Samalin, L., Llorca, PM., Mennetrier, M., Bonnet, T., Lacelle, D., Vayssié, M., Beal, C., Blanc, O., Zachos, Kassandra A., Choi, Jaehyoung, Godin, Ophelia, Chernega, Timofei, Kwak, Haejin Angela, Jung, Jae H., Aouizerate, Bruno, Aubin, Valérie, Bellivier, Frank, Belzeaux-R, Raoul, Courtet, Philippe, Dubertret, Caroline, Etain, Bruno, Haffen, Emmanuel, Lefrere A, Antoine, Llorca, Pierre-Michel, Olié, Emilie, Polosan, Mircea, Samalin, Ludovic, Schwan, Raymund, Roux, Paul, Barau, Caroline, Richard, Jean Romain, Tamouza, Ryad, Leboyer, Marion, and Andreazza, Ana C.

Published
2024
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5. Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort

Author

Etain, B., Olié, E., Leboyer, M., Haffen, E., Llorca, P.M., Barteau, V., Bensalem, S., Godin, O., Laouamri, H., Souryis, K., Hotier, S., Pelletier, A., Drancourt, N., Sanchez, J.P., Saliou, E., Hebbache, C., Petrucci, J., Willaume, L., Bourdin, E., Bellivier, F., Carminati, M., Marlinge, E., Meheust, J., Hennion, V., Francisque, H., Aouizerate, B., Da Ros, N., Desage, A., Elkael, C., Gard, S., Hoorelbeke, F., M'bailara, K., Minois, I., Sportich, J., Boukhobza, L., Benramdane, M., Courtet, P., Deffinis, B., Denat, S., Ducasse, D., Gachet, M., Molière, F., Nass, L., Tarquini, G., Belzeaux, R., Cermolacce, M., Groppi, F., Moreau, E., Lefrere, A., Lescalier, L., Pastol, J., Viglianese, N., Cohen, R., Gross, G., Schwan, R., Schwitzer, T., Wajsbrot-Elgrabli, O., Bougerol, T., Fredembach, B., Denoual, Q, Bertrand, A., Pouchon, A., Polosan, M., Bonny, G., Brehon, L., Durand, L., Feuga, V., Galliot, A.M., Kayser, N., Passerieux, C., Roux, P., Aubin, V., Cussac, I., Dupont, M.A., Loftus, J., Medecin, I., Dubertret, C., Mazer, N., Portalier, C., Scognamiglio, C., Bing, A., Laurent, P., Llorca, PM., Samalin, L., Foures, L., Lacelle, D., Pires, S., Doriat, C., Blanc, O., Bennabi, D., Nicolier, M., Vidal, N., Brunet-Gouet, E., Frileux, S., D'Amato, T., Januel, D., and Walter, M.

Published
2023
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6. Validation of a data collection set for the psychiatric, addiction, sleep and chronobiological assessments of patients with depression: A Delphi study for the SoPsy-depression French national cohort

Author

Philip, P., Arnulf, I., Royant-Parola, S., Leger, D., Gohier, B., Gagnadoux, F., Amad, A., Poirot, I., Gaillard, R., Limosin, F., Delorme, R., Jardri, R., Fossati, P., Dubertret, C., Rolland, B., Etain, B., Vorspan, F., Aouizerate, B., Courtet, P., Castroman, J.L., Haffen, E., Drapier, D., Dereux, A., Schwan, R., Luquiens, A., Abril, B., Auriacombe, M., Benyamina, A., Lopez, R., Grall-Bronnec, M., Bennabi, D., Frija-Masson, J., Micoulaud Franchi, J.-A., Schwitzer, T., Maranci, J.-B., Huck, U.K., Geoffroy, P.A., Schroder, C.M., Bourgin, P., Maruani, J., Lejoyeux, M., d’Ortho, M.-P., and Couffignal, C.

Published
2023
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8. Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort

Author

Etain, B., Olié, E., Leboyer, M., Llorca, P.M., Barteau, V., Bensalem, S., Godin, O., Laouamri, H., Souryis, K., Hotier, S., Pelletier, A., Sanchez, J.P., Saliou, E., Hebbache, C., Petrucci, J., Wuillaume, L., Bourdin, E., Bellivier, F., Carminati, M., Hennion, V., Marlinge, E., Meheust, J., Zekri, C., Desage, A., Gard, S., M'Bailara, K., Minois, I., Sportich, J., Zanouy, L., Abettan, C., Bardin, L., Cazals, A., Courtet, P., Deffinis, B., Ducasse, D., Gachet, M., Henrion, A., Martinerie, E., Molière, F., Noisette, B., Tarquini, E.G., Aubin, V., Belzeaux, R., Costagliola, D., Dubertret, C., Haffen, E., Henry, C., Passerieux, C., Polosan, M., Roux, P., Schwan, R., Samalin, L., and Etain, Bruno

Published
2022
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10. Clinical characteristics of bipolar disorders with postpartum depressive onset

Author

Etain, B., Henry, C., Olié, E., Leboyer, M., Haffen, E., Llorca, P.M., Barteau, V., Bensalem, S., Godin, O., Laouamri, H., Souryis, K., Hotier, S., Pelletier, A., Drancourt, N., Sanchez, J.P., Saliou, E., Hebbache, C., Petrucci, J., Willaume, L., Bourdin, E., Bellivier, F., Carminati, M., Marlinge, E., Meheust, J., Antoniol, B., Desage, A., Gard, S., Jutant, A., Mbailara, K., Minois, I., Zanouy, L., Abettan, C., Bardin, L., Cazals, A., Courtet, P., Deffinis, B., Ducasse, D., Gachet, M., Henrion, A., Martinerie, E., Molière, F., Noisette, B., Tarquini, G., Azorin, J.M., Belzeaux, R., Correard, N., Consoloni, J.L., Groppi, F., Lescalier, L., Montant, J., Rebattu, M., Viglianese, N., Cohen, R., Kahn, J.P., Milazzo, M., Wajsbrot-Elgrabli, O., Bougerol, T., Fredembach, B., Suisse, A., Halili, B., Pouchon, A., Polosan, M., Galliot, A.M., Grévin, I., Cannavo, A.S., Kayser, N., Passerieux, C., Roux, P., Aubin, V., Cussac, I., Dupont, M.A., Loftus, J., Medecin, I., Dubertret, C., Mazer, N., Portalier, C., Scognamiglio, C., Bing, A., Tebeka, Sarah, Godin, Ophelia, Mazer, Nicolas, Bellivier, Frank, Courtet, Philippe, Etain, Bruno, Gard, Sébastien, Leboyer, Marion, Llorca, Pierre-Michel, Loftus, Joséphine, Olié, Emilie, Passerieux, Christine, Polosan, Mircea, Schwan, Raymund, Belzeaux, Raoul, and Dubertret, Caroline

Published
2021
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11. Clinical predictors of recurrences in bipolar disorders type 1 and 2: A FACE-BD longitudinal study

Author

Etain, B., Olié, E., Leboyer, M., Llorca, P.M., Henry, C., Barteau, V., Bensalem, S., Godin, O., Laouamri, H., Souryis, K., Hotier, S., Pelletier, A., Sanchez, J.P., Saliou, E., Hebbache, C., Petrucci, J., Willaume, L., Bourdin, E., Bellivier, F., Carminati, M., Maruani, J., Marlinge, E., Meheust, J., Antoniol, B., Desage, A., Gard, S., Jutant, A., Mbailara, K., Minois, I., Zanouy, L., Abettan, C., Bardin, L., Cazals, A., Courtet, P., Deffinis, B., Ducasse, D., Gachet, M., Henrion, A., Martinerie, E., Molière, F., Noisette, B., Tarquini, G., Azorin, J.M., Belzeaux, R., Correard, N., Consoloni, J.L., Groppi, F., Lescalier, L., Montant, J., Rebattu, M., Viglianese, N., Cohen, R., Gross, G., Schwan, R., Schwitzer, T., Wajsbrot-Elgrabli, O., Bougerol, T., Fredembach, B., Suisse, A., Halili, B., Gaoua, Z., Polosan, M., Cannavo, A.S., Galliot, A.M., Grévin, I., Kayser, N., Liaskovski, G., Passerieux, C., Roux, P., Aubin, V., Cussac, I., Dupont, M.A., Loftus, J., Medecin, I., Dubertret, C., Mazer, N., Portalier, C., Scognamiglio, C., Bing, A., and Aouizerate, B.

Published
2021
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12. Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort

Author

Samalin, L., Godin, O., Olié, E., Etain, B., Henry, C., Pelletier, A., Poinso, F., Encely, L., Mazer, N., Roux, P., Loftus, J, Gard, S., Bennabi, D., Polosan, M., Schwitzer, T., Aubin, V., Schwan, R., Passerieux, C., Bougerol, T., Dubertret, C., Aouizerate, B., Haffen, E., Courtet, P., Bellivier, F., Leboyer, M., Llorca, P.M., and Belzeaux, R.

Published
2020
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19. Childhood trauma, dimensions of psychopathology and the clinical expression of bipolar disorders: A pathway analysis

Author

Henry, C., Etain, B., Leboyer, M., Laouamri, H., Souryis, K., Godin, O., Raust, A., Sportiche, S., Geoffroy, P.A., Aouizerate, B., Desage, A., Olie, E., Ducasse, D., Moliere, F., Belzeaux, R., Viglianaise, N., Lescalier, L., Job, S., Cohen, R., Wajsbrot-Elgrabli, O., Polosan, M., Garcon, S., Hardy-Bayle, M.C., Roux, P., Kayser, N., Grevin, I., Loftus, J., Albertini, L., Lajnef, M., Aubin, V., Azorin, J.M., Bellivier, F., Bougerol, T., Courtet, P., Gard, S., Kahn, J.P., and Passerieux, C.

Published
2017
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30. Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

Author

Bauer, M., Glenn, T., Alda, M., Andreassen, O.A., Angelopoulos, E., Ardau, R., Baethge, C., Bauer, R., Bellivier, F., Belmaker, R.H., Berk, M., Bjella, T.D., Bossini, L., Bersudsky, Y., Cheung, E.Y.W., Conell, J., Del Zompo, M., Dodd, S., Etain, B., Fagiolini, A., Frye, M.A., Fountoulakis, K.N., Garneau-Fournier, J., Gonzalez-Pinto, A., Harima, H., Hassel, S., Henry, C., Iacovides, A., Isometsä, E.T., Kapczinski, F., Kliwicki, S., König, B., Krogh, R., Kunz, M., Lafer, B., Larsen, E.R., Lewitzka, U., Lopez-Jaramillo, C., MacQueen, G., Manchia, M., Marsh, W., Martinez-Cengotitabengoa, M., Melle, I., Monteith, S., Morken, G., Munoz, R., Nery, F.G., O’Donovan, C., Osher, Y., Pfennig, A., Quiroz, D., Ramesar, R., Rasgon, N., Reif, A., Ritter, P., Rybakowski, J.K., Sagduyu, K., Scippa, A.M., Severus, E., Simhandl, C., Stein, D.J., Strejilevich, S., Hatim Sulaiman, A., Suominen, K., Tagata, H., Tatebayashi, Y., Torrent, C., Vieta, E., Viswanath, B., Wanchoo, M.J., Zetin, M., and Whybrow, P.C.

Published
2015
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39. Childhood maltreatment and metabolic syndrome in bipolar disorders: In search of moderators

Author

Etain, B., Henry, C., Olié, E., Leboyer, M., Haffen, E., Llorca, PM, Barteau, V., Bensalem, S., Godin, O., Laouamri, H., Souryis, K., Hotier, S., Pelletier, A., Drancourt, N., Sanchez, JP., Saliou, E., Hebbache, C., Petrucci, J., Willaume, L., Bourdin, E., Bellivier, F., Carminati, M., Marlinge, E., Meheust, J., Meyrel, M., Aouizerate, B., Desage, A., Gard, S., Sportich, J, Mbailara, K., Minois, I., Zanouy, L., Bardin, L., Cazals, A., Courtet, P., Deffinis, B., Ducasse, D., Gachet, M., Henrion, A., Moliere, F., Noisette, B., Olie, E., Tarquini, G., Belzeaux, R., Correard, N., Groppi, F., Lefrere, A., Lescalier, L., Moreau, E., Pastol, J., Rebattu, M., Roux, B., Viglianese, N., Cohen, R., Schwan, Raymond, Kahn, J.P., Milazzo, M., Wajsbrot-Elgrabli, O., Bougerol, T., Fredembach, B., Suisse, A., Halili, B., Pouchon, A, Polosan, M., Galliot, A.M., Grévin, I., Cannavo, A.S., Kayser, N., Passerieux, C., Roux, P., Service de Psychiatrie, Aubin, V., Cussac, I., Dupont, M.A, Loftus, J., Medecin, I., Dubertret, C., Mazer, N., Portalier, C., Scognamiglio, C., Bing, A., Godin, Ophelia, Gaube, Géraud, Olié, Emilie, Belzeaux, Raoul, Bellivier, Frank, Loftus, Joséphine, Courtet, Philippe, Dubertret, Caroline, llorca, Pierre-Michel, Gard, Sebastien, Henry, Chantal, Schwan, Raymund, Passerieux, Christine, Polosan, Mircea, Samalin, Ludovic, Leboyer, Marion, and Etain, Bruno

Published
2021
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40. Future directions in the field of Bipolar Disorder

Author

Bauer, M., Bechdolf, A., Bellivier, F., Bergink, V., Ceylan, D., Correll, C.U., Etain, B., Fagiolini, A., Geddes, J., Gonzalez-Pinto, A., Goodwin, G., Hajek, T., Henry, C., Kessing, L.V., Kupka, R., Lagerberg, T.V., Landen, M., Licht, R.W., Martinez-Cengotitabengoa, M., Morken, G., Nielsen, R.E., Rietschel, M., Ritter, P., Schulze, T., Scott, J., Severus, E., Squassina, A., Suwalska, A., Vieta, E., Yildiz, A., Reininghaus, E.Z., Dalkner, N., Wels, L., Stijic, M., Reif, A., Manchia, M., and Andreassen, O.A.

Published
2024
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42. HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Author

Le Clerc, S, Lombardi, L, Baune, BT, Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Jamain, S, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, JR, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, Colom, F, Millischer, V, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O’Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Pisanu, C, Squassina, A, Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235, Le Clerc, S, Lombardi, L, Baune, BT, Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Jamain, S, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, JR, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, Colom, F, Millischer, V, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O’Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Pisanu, C, Squassina, A, and Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235

Abstract

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.

Published
2021

44. Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Author

Kalman, JL, Papiol, S, Forstner, AJ, Heilbronner, U, Degenhardt, F, Strohmaier, J, Adli, M, Adorjan, K, Akula, N, Alda, M, Anderson-Schmidt, H, Andlauer, TFM, Anghelescu, IG, Ardau, R, Arias, B, Arolt, V, Aubry, JM, Backlund, L, Bartholdi, K, Bauer, M, Baune, BT, Becker, T, Bellivier, F, Benabarre, A, Bengesser, S, Bhattacharjee, AK, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Budde, M, Cervantes, P, Chillotti, C, Cichon, S, Clark, SR, Colom, F, Comes, AL, Cruceanu, C, Czerski, PM, Dannlowski, U, Dayer, A, Del Zompo, M, DePaulo, JR, Dietrich, DE, Étain, B, Ethofer, T, Falkai, P, Fallgatter, A, Figge, C, Flatau, L, Folkerts, H, Frisen, L, Frye, MA, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Gade, K, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Gryaznova, A, Hake, M, Hauser, J, Herms, S, Hoffmann, P, Hou, L, Jäger, M, Jamain, S, Jiménez, E, Juckel, G, Kahn, JP, Kassem, L, Kelsoe, J, Kittel-Schneider, S, Kliwicki, S, Klohn-Sagatholislam, F, Koller, M, König, B, Konrad, C, Lackner, N, Laje, G, Landén, M, Lang, FU, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, McMahon, FJ, Mitchell, PB ; https://orcid.org/0000-0002-7954-5235, Mitjans, M, Mondimore, FM, Monteleone, P, Nieratschker, V, Nievergelt, CM, Novák, T, Ösby, U, Pfennig, A, Potash, JB, Schofield, Peter ; https://orcid.org/0000-0003-2967-9662, Kalman, JL, Papiol, S, Forstner, AJ, Heilbronner, U, Degenhardt, F, Strohmaier, J, Adli, M, Adorjan, K, Akula, N, Alda, M, Anderson-Schmidt, H, Andlauer, TFM, Anghelescu, IG, Ardau, R, Arias, B, Arolt, V, Aubry, JM, Backlund, L, Bartholdi, K, Bauer, M, Baune, BT, Becker, T, Bellivier, F, Benabarre, A, Bengesser, S, Bhattacharjee, AK, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Budde, M, Cervantes, P, Chillotti, C, Cichon, S, Clark, SR, Colom, F, Comes, AL, Cruceanu, C, Czerski, PM, Dannlowski, U, Dayer, A, Del Zompo, M, DePaulo, JR, Dietrich, DE, Étain, B, Ethofer, T, Falkai, P, Fallgatter, A, Figge, C, Flatau, L, Folkerts, H, Frisen, L, Frye, MA, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Gade, K, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Gryaznova, A, Hake, M, Hauser, J, Herms, S, Hoffmann, P, Hou, L, Jäger, M, Jamain, S, Jiménez, E, Juckel, G, Kahn, JP, Kassem, L, Kelsoe, J, Kittel-Schneider, S, Kliwicki, S, Klohn-Sagatholislam, F, Koller, M, König, B, Konrad, C, Lackner, N, Laje, G, Landén, M, Lang, FU, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, McMahon, FJ, Mitchell, PB ; https://orcid.org/0000-0002-7954-5235, Mitjans, M, Mondimore, FM, Monteleone, P, Nieratschker, V, Nievergelt, CM, Novák, T, Ösby, U, Pfennig, A, Potash, JB, and Schofield, Peter ; https://orcid.org/0000-0003-2967-9662

Abstract

Objectives: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. Methods: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. Results: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. Conclusions: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.

Published
2019

47. Analysis of the influence of microRNAs in lithium response in bipolar disorder

Author

Reinbold, CS, Forstner, AJ, Hecker, J, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Hoffmann, P, Hou, L, Heilbronner, U, Degenhardt, F, Adli, M, Akiyama, K, Akula, N, Ardau, R, Arias, B, Backlund, L, Benabarre, A, Bengesser, S, Bhattacharjee, AK, Biernacka, JM, Birner, A, Marie-Claire, C, Cervantes, P, Chen, GB, Chen, HC, Chillotti, C, Clark, SR, Colom, F, Cousins, DA, Cruceanu, C, Czerski, PM, Dayer, A, Étain, B, Falkai, P, Frisén, L, Gard, S, Garnham, JS, Goes, FS, Grof, P, Gruber, O, Hashimoto, R, Hauser, J, Herms, S, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Lackner, N, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Jaramillo, CAL, MacQueen, G, Manchia, M, Martinsson, L, Mattheisen, M, McCarthy, MJ, McElroy, SL, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Ösby, U, Ozaki, N, Perlis, RH, Pfennig, A, Reich-Erkelenz, D, Rouleau, GA, Schofield, PR ; https://orcid.org/0000-0003-2967-9662, Schubert, KO, Schweizer, BW, Seemüller, F, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Smoller, JW, Squassina, A, Stamm, TJ, Stopkova, P, Tighe, SK, Tortorella, A, Turecki, G, Volkert, J, Witt, SH, Wright, AJ, Trevor Young, L, Zandi, PP, Potash, JB, DePaulo, JR, Bauer, M, Reininghaus, E, Novák, T, Aubry, JM, Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235, Reinbold, CS, Forstner, AJ, Hecker, J, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Hoffmann, P, Hou, L, Heilbronner, U, Degenhardt, F, Adli, M, Akiyama, K, Akula, N, Ardau, R, Arias, B, Backlund, L, Benabarre, A, Bengesser, S, Bhattacharjee, AK, Biernacka, JM, Birner, A, Marie-Claire, C, Cervantes, P, Chen, GB, Chen, HC, Chillotti, C, Clark, SR, Colom, F, Cousins, DA, Cruceanu, C, Czerski, PM, Dayer, A, Étain, B, Falkai, P, Frisén, L, Gard, S, Garnham, JS, Goes, FS, Grof, P, Gruber, O, Hashimoto, R, Hauser, J, Herms, S, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Lackner, N, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Jaramillo, CAL, MacQueen, G, Manchia, M, Martinsson, L, Mattheisen, M, McCarthy, MJ, McElroy, SL, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Ösby, U, Ozaki, N, Perlis, RH, Pfennig, A, Reich-Erkelenz, D, Rouleau, GA, Schofield, PR ; https://orcid.org/0000-0003-2967-9662, Schubert, KO, Schweizer, BW, Seemüller, F, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Smoller, JW, Squassina, A, Stamm, TJ, Stopkova, P, Tighe, SK, Tortorella, A, Turecki, G, Volkert, J, Witt, SH, Wright, AJ, Trevor Young, L, Zandi, PP, Potash, JB, DePaulo, JR, Bauer, M, Reininghaus, E, Novák, T, Aubry, JM, and Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235

Abstract

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs

Published
2018

48. Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study

Author

Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, J, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O'Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR ; https://orcid.org/0000-0003-2967-9662, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Maj, M, Turecki, G, Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235, Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM ; https://orcid.org/0000-0003-4014-4490, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, J, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O'Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR ; https://orcid.org/0000-0003-2967-9662, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Maj, M, Turecki, G, and Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235

Abstract

IMPORTANCE Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). OBJECTIVES To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. DESIGN, SETTING, AND PARTICIPANTS A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013.Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. MAIN OUTCOMES AND MEASURES Treatment response to lithiumwas defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. RESULTS Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 ? 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95%

Published
2018

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