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374 results on '"Andreassen, O.A."'

1. Future directions in the field of Bipolar Disorder

Author

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

Published
2024
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9. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author

Schijven, Dick, Postema, M.C., Fukunaga, M., Matsumoto, J., Miura, K., Zwarte, S.M.C. de, Haren, N.E.M. van, Cahn, W., Hulshoff Pol, H.E., Kahn, R.S., Ayesa-Arriola, R., Ortoz-García de la Foz, V., Tordesillas-Gutierrez, D., Vázquez-Bourgon, J., Crespo-Facorro, B., Alnæs, D., Dahl, A., Westlye, L.T., Agartz, I., Andreassen, O.A., Jönsson, E.G., Kochunov, P., Bruggemann, J.M., Catts, S.V., Michie, P.T., Mowry, B.J., Quidé, Y., Rasser, P.E., Schall, U., Scott, R.J., Carr, V.J., Green, M.J., Henskens, F.A., Loughland, C.M., Pantelis, C., Weickert, C.S., Weickert, T.W., Haan, L. de, Brosch, K., Pfarr, J.K., Ringwald, K.G., Stein, F., Jansen, Andreas, Kircher, T.T.J., Nenadić, I., Krämer, Bernd, Gruber, O., Satterthwaite, T.D., Bustillo, J., Mathalon, D.H., Preda, A., Calhoun, V.D., Ford, J.M., Potkin, S.G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, F., Ehrlich, S., Fuentes-Claramonte, P., Garcia-Leon, M.A., Guerrero-Pedraza, A., Salvador, R., Sarró, S., Pomarol-Clotet, E., Ciullo, V., Piras, F., Vecchio, D., Banaj, N., Spalletta, G., Michielse, S., Amelsvoort, T. van, Dickie, E.W., Voineskos, A.N., Sim, K., Ciufolini, S., Dazzan, P., Murray, R.M., Kim, W.S., Chung, Y.C., Andreou, C., Schmidt, A, Borgwardt, S., McIntosh, A.M., Whalley, H.C., Lawrie, S.M., Plessis, S. du, Luckhoff, H.K., Scheffler, F., Emsley, R., Grotegerd, D., Lencer, R., Dannlowski, U., Edmond, J.T., Rootes-Murdy, K., Stephen, J.M., Mayer, A.R., Antonucci, L.A., Fazio, L., Pergola, G., Bertolino, A., Díaz-Caneja, C.M., Janssen, J, Lois, N.G., Arango, C., Tomyshev, A.S., Lebedeva, I., Cervenka, S., Sellgren, C.M., Georgiadis, F., Kirschner, M., Kaiser, S., Hajek, T., Skoch, A., Spaniel, F., Kim, M., Kwak, Y.B., Oh, S., Kwon, J.S., James, A., Bakker, G., Knöchel, C., Stäblein, M., Oertel, V., Uhlmann, A., Howells, F.M., Stein, D.J., Temmingh, H.S., Diaz-Zuluaga, A.M., Pineda-Zapata, J.A., López-Jaramillo, C., Homan, S., Ji, E., Surbeck, W., Homan, P., Fisher, S.E., Franke, B., Glahn, D.C., Gur, R.C., Hashimoto, R., Jahanshad, N., Luders, E., Medland, S.E., Thompson, P.M., Turner, J.A., Erp, T.G. van, Francks, C., Schijven, Dick, Postema, M.C., Fukunaga, M., Matsumoto, J., Miura, K., Zwarte, S.M.C. de, Haren, N.E.M. van, Cahn, W., Hulshoff Pol, H.E., Kahn, R.S., Ayesa-Arriola, R., Ortoz-García de la Foz, V., Tordesillas-Gutierrez, D., Vázquez-Bourgon, J., Crespo-Facorro, B., Alnæs, D., Dahl, A., Westlye, L.T., Agartz, I., Andreassen, O.A., Jönsson, E.G., Kochunov, P., Bruggemann, J.M., Catts, S.V., Michie, P.T., Mowry, B.J., Quidé, Y., Rasser, P.E., Schall, U., Scott, R.J., Carr, V.J., Green, M.J., Henskens, F.A., Loughland, C.M., Pantelis, C., Weickert, C.S., Weickert, T.W., Haan, L. de, Brosch, K., Pfarr, J.K., Ringwald, K.G., Stein, F., Jansen, Andreas, Kircher, T.T.J., Nenadić, I., Krämer, Bernd, Gruber, O., Satterthwaite, T.D., Bustillo, J., Mathalon, D.H., Preda, A., Calhoun, V.D., Ford, J.M., Potkin, S.G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, F., Ehrlich, S., Fuentes-Claramonte, P., Garcia-Leon, M.A., Guerrero-Pedraza, A., Salvador, R., Sarró, S., Pomarol-Clotet, E., Ciullo, V., Piras, F., Vecchio, D., Banaj, N., Spalletta, G., Michielse, S., Amelsvoort, T. van, Dickie, E.W., Voineskos, A.N., Sim, K., Ciufolini, S., Dazzan, P., Murray, R.M., Kim, W.S., Chung, Y.C., Andreou, C., Schmidt, A, Borgwardt, S., McIntosh, A.M., Whalley, H.C., Lawrie, S.M., Plessis, S. du, Luckhoff, H.K., Scheffler, F., Emsley, R., Grotegerd, D., Lencer, R., Dannlowski, U., Edmond, J.T., Rootes-Murdy, K., Stephen, J.M., Mayer, A.R., Antonucci, L.A., Fazio, L., Pergola, G., Bertolino, A., Díaz-Caneja, C.M., Janssen, J, Lois, N.G., Arango, C., Tomyshev, A.S., Lebedeva, I., Cervenka, S., Sellgren, C.M., Georgiadis, F., Kirschner, M., Kaiser, S., Hajek, T., Skoch, A., Spaniel, F., Kim, M., Kwak, Y.B., Oh, S., Kwon, J.S., James, A., Bakker, G., Knöchel, C., Stäblein, M., Oertel, V., Uhlmann, A., Howells, F.M., Stein, D.J., Temmingh, H.S., Diaz-Zuluaga, A.M., Pineda-Zapata, J.A., López-Jaramillo, C., Homan, S., Ji, E., Surbeck, W., Homan, P., Fisher, S.E., Franke, B., Glahn, D.C., Gur, R.C., Hashimoto, R., Jahanshad, N., Luders, E., Medland, S.E., Thompson, P.M., Turner, J.A., Erp, T.G. van, and Francks, C.

Abstract

Item does not contain fulltext, Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Published
2023

10. Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders.

Author

Segal, A., Parkes, L., Aquino, K., Kia, S.M., Wolfers, T., Franke, B., Hoogman, M., Beckmann, C.F., Westlye, L.T., Andreassen, O.A., Zalesky, A., Harrison, B.J., Davey, C.G., Soriano-Mas, C., Cardoner, N., Tiego, J., Yücel, M., Braganza, L., Suo, C., Berk, M., Cotton, S., Bellgrove, M.A., Marquand, A.F., Fornito, A., Segal, A., Parkes, L., Aquino, K., Kia, S.M., Wolfers, T., Franke, B., Hoogman, M., Beckmann, C.F., Westlye, L.T., Andreassen, O.A., Zalesky, A., Harrison, B.J., Davey, C.G., Soriano-Mas, C., Cardoner, N., Tiego, J., Yücel, M., Braganza, L., Suo, C., Berk, M., Cotton, S., Bellgrove, M.A., Marquand, A.F., and Fornito, A.

Abstract

01 september 2023, Contains fulltext : 296133.pdf (Publisher’s version ) (Open Access), The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.

Published
2023

11. Initiation of the European multicentre study “bipcom” to unravel medical comorbidities in bipolar disorder

Author

Kobayashi, N.F., Garcia-Argibay, Miguel, Andreassen, O.A., Leboyer, M., Corcoy, R., Florian, K., Michael, B., Reif, A., De Girolamo, G., Kobayashi, N.F., Garcia-Argibay, Miguel, Andreassen, O.A., Leboyer, M., Corcoy, R., Florian, K., Michael, B., Reif, A., and De Girolamo, G.

Abstract

Background: Bipolar Disorder (BD) is a severe and heritable psychiatric disorder. It represents a substantial public health problem, due to its prevalence, its high degree of disability and psychiatric and somatic comorbidities, especially cardiometabolic disturbances. Such comorbidities pose a significant additive burden for patients with BD. Considering the clinical heterogeneity of these patients, a better characterization of this population is required to develop personalised treatment approaches. Objective: BIPCOM is a multicentre study funded by the EU within the ERAperMed Call, involving six centres from different countries (Italy, France, Germany, Norway, Spain, Sweden). The purpose of BIPCOM is to identify somatic comorbidities in BD patients to develop precision medicine approaches. Aims: BIPCOM aims to define the prevalence rates, risk and protective factors and the natural course of somatic comorbidities of BD patients. Those data will be integrated to develop a tool to support individualized clinical decision-making in BD. Method: BIPCOM comprises three separate clinical studies to define patient characteristics and a subsequent exploitation element. In the first study, data will be obtained from the Nordic biobanks and medical registries. In the second study, the study centres together will contribute standardized data of at least 1500 patients comprising 24 pre-specified variables (among others past and current comorbidities and treatment). Emphasis will be given to chronic somatic disorders (diabetes mellitus, metabolic syndrome, dyslipidaemia, obesity or endocrine disorders). The third study has a prospective element with in depth characterization of 400 patients including a one-year follow up with a focus on metabolic syndrome. Patients aged from 18 – 65 with a primary diagnosis of BD, who had at least one contact with mental health services in the last year will be included. A “patient schedule” will include each participant’s socio-demographic, c

Published
2023
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12. 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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16. Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study

Author

Tissink, E.P., primary, Shadrin, A.A., additional, van der Meer, D., additional, Parker, N., additional, Hindley, G., additional, Roelfs, D., additional, Frei, O., additional, Fan, C.C., additional, Nagel, M., additional, Nærland, T., additional, Budisteanu, M., additional, Djurovic, S., additional, Westlye, L. T., additional, van den Heuvel, M.P., additional, Posthuma, D., additional, Kaufmann, T., additional, Dale, A.M., additional, and Andreassen, O.A., additional

Published
2022
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18. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author

Dima, D., Modabbernia, A., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dannlowski, U., Dale, A.M., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., Kalnin, A., Naaijen, J., Klein, M., Thompson, P.M., Frangou, S., Dima, D., Modabbernia, A., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dannlowski, U., Dale, A.M., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., Kalnin, A., Naaijen, J., Klein, M., Thompson, P.M., and Frangou, S.

Abstract

Contains fulltext : 245411.pdf (Publisher’s version ) (Open Access), Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Published
2022

19. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Author

Frangou, S., Modabbernia, A., Williams, S.C.R., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dale, A.M., Dannlowski, U., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., Klein, M., Frangou, S., Modabbernia, A., Williams, S.C.R., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dale, A.M., Dannlowski, U., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., and Klein, M.

Abstract

Contains fulltext : 245396.pdf (Publisher’s version ) (Open Access), Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Published
2022

20. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author

Blokland, G.A., Grove, J, Chen, C.Y., Cotsapas, C., Tobet, S., Handa, R., Clair, D. St, Lencz, T., Mowry, B.J., Periyasamy, S., Cairns, M.J., Tooney, P.A., Wu, J.Q., Kelly, B., Kirov, G., Sullivan, P.F., Corvin, A., Riley, B.P., Esko, T., Milani, L., Jönsson, E.G., Palotie, A., Ehrenreich, H., Begemann, M., Steixner-Kumar, A., Sham, P.C., Iwata, N., Weinberger, D.R., Gejman, P.V., Sanders, A.R., Buxbaum, J.D., Rujescu, D., Giegling, I., Konte, B., Hartmann, A.M., Bramon, E., Murray, R.M., Pato, M.T., Lee, J., Melle, I., Molden, E., Ophoff, R.A., McQuillin, A., Bass, N.J., Adolfsson, R., Malhotra, A.K., Martin, N.G., Fullerton, J.M., Mitchell, P.B., Schofield, P.R., Forstner, A.J., Degenhardt, F., Schaupp, S., Comes, A.L., Kogevinas, M., Guzman-Parra, J., Reif, A., Streit, F., Sirignano, L., Cichon, S., Grigoroiu-Serbanescu, M., Hauser, J., Lissowska, J., Mayoral, F., Müller-Myhsok, B., Świątkowska, B., Schulze, T.G., Nöthen, M.M., Rietschel, M., Kelsoe, J., Leboyer, M., Jamain, S., Etain, B., Bellivier, F., Vincent, J.B., Alda, M., O'Donovan, C., Cervantes, P., Biernacka, J.M., Frye, M., McElroy, S.L., Scott, L.J., Stahl, E.A., Landén, M., Hamshere, M.L., Smeland, O.B., Djurovic, S., Vaaler, A.E., Andreassen, O.A., Baune, B.T., Air, T., Preisig, M., Uher, R., Levinson, D.F., Weissman, M.M., Potash, J.B., Shi, J., Knowles, J.A., Bralten, J.B., Perlis, R.H., Lucae, S., Blokland, G.A., Grove, J, Chen, C.Y., Cotsapas, C., Tobet, S., Handa, R., Clair, D. St, Lencz, T., Mowry, B.J., Periyasamy, S., Cairns, M.J., Tooney, P.A., Wu, J.Q., Kelly, B., Kirov, G., Sullivan, P.F., Corvin, A., Riley, B.P., Esko, T., Milani, L., Jönsson, E.G., Palotie, A., Ehrenreich, H., Begemann, M., Steixner-Kumar, A., Sham, P.C., Iwata, N., Weinberger, D.R., Gejman, P.V., Sanders, A.R., Buxbaum, J.D., Rujescu, D., Giegling, I., Konte, B., Hartmann, A.M., Bramon, E., Murray, R.M., Pato, M.T., Lee, J., Melle, I., Molden, E., Ophoff, R.A., McQuillin, A., Bass, N.J., Adolfsson, R., Malhotra, A.K., Martin, N.G., Fullerton, J.M., Mitchell, P.B., Schofield, P.R., Forstner, A.J., Degenhardt, F., Schaupp, S., Comes, A.L., Kogevinas, M., Guzman-Parra, J., Reif, A., Streit, F., Sirignano, L., Cichon, S., Grigoroiu-Serbanescu, M., Hauser, J., Lissowska, J., Mayoral, F., Müller-Myhsok, B., Świątkowska, B., Schulze, T.G., Nöthen, M.M., Rietschel, M., Kelsoe, J., Leboyer, M., Jamain, S., Etain, B., Bellivier, F., Vincent, J.B., Alda, M., O'Donovan, C., Cervantes, P., Biernacka, J.M., Frye, M., McElroy, S.L., Scott, L.J., Stahl, E.A., Landén, M., Hamshere, M.L., Smeland, O.B., Djurovic, S., Vaaler, A.E., Andreassen, O.A., Baune, B.T., Air, T., Preisig, M., Uher, R., Levinson, D.F., Weissman, M.M., Potash, J.B., Shi, J., Knowles, J.A., Bralten, J.B., Perlis, R.H., and Lucae, S.

Abstract

Item does not contain fulltext, BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and

Published
2022

21. Greater male than female variability in regional brain structure across the lifespan

Author

Wierenga, L.M., Doucet, G.E., Dima, D., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andreassen, O.A., Anticevic, A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Braber, A., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Calhoun, V.D., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Chaim-Avancini, T.M., Ching, C.R., Clark, V.P., Conrod, P.J., Conzelmann, A., Crivello, F., Davey, C.G., Dickie, E.W., Ehrlich, S., Ent, D. van 't, Fisher, S.E., Fouche, J.P., Franke, B., Fuentes-Claramonte, P., Geus, E.J. de, Giorgio, A. Di, Glahn, D.C., Gotlib, I.H., Grabe, H.J., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Gurholt, T.P., Haan, L. de, Haatveit, B., Harrison, B.J., Hartman, C.A., Hatton, S.N., Heslenfeld, D.J., Heuvel, O.A. van den, Hickie, I.B., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A.C., Jiang, J., Jönsson, E.G., Joska, J.A., Kalnin, A.J., Klein, M., Koenders, L., Kolskår, K.K., Krämer, B., Kuntsi, J., Lagopoulos, J., Lazaro, L., Lebedeva, I.S., Lee, Phil H., Lochner, C., Machielsen, M.W., Maingault, S., Martin, N.G., Martínez-Zalacaín, I., Mataix-Cols, D., Mazoyer, B., McDonald, B.C., McDonald, C., McIntosh, A.M., McMahon, K.L., McPhilemy, G., Naaijen, J., Frangou, S., Tamnes, C.K., Wierenga, L.M., Doucet, G.E., Dima, D., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andreassen, O.A., Anticevic, A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Braber, A., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Calhoun, V.D., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Chaim-Avancini, T.M., Ching, C.R., Clark, V.P., Conrod, P.J., Conzelmann, A., Crivello, F., Davey, C.G., Dickie, E.W., Ehrlich, S., Ent, D. van 't, Fisher, S.E., Fouche, J.P., Franke, B., Fuentes-Claramonte, P., Geus, E.J. de, Giorgio, A. Di, Glahn, D.C., Gotlib, I.H., Grabe, H.J., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Gurholt, T.P., Haan, L. de, Haatveit, B., Harrison, B.J., Hartman, C.A., Hatton, S.N., Heslenfeld, D.J., Heuvel, O.A. van den, Hickie, I.B., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A.C., Jiang, J., Jönsson, E.G., Joska, J.A., Kalnin, A.J., Klein, M., Koenders, L., Kolskår, K.K., Krämer, B., Kuntsi, J., Lagopoulos, J., Lazaro, L., Lebedeva, I.S., Lee, Phil H., Lochner, C., Machielsen, M.W., Maingault, S., Martin, N.G., Martínez-Zalacaín, I., Mataix-Cols, D., Mazoyer, B., McDonald, B.C., McDonald, C., McIntosh, A.M., McMahon, K.L., McPhilemy, G., Naaijen, J., Frangou, S., and Tamnes, C.K.

Abstract

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access), For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Published
2022

22. Closing the life-cycle of normative modeling using federated hierarchical Bayesian regression

Author

Kia, S.M., Huijsdens, H., Rutherford, S.E.R., Boer, A.A.A. de, Dinga, R., Wolfers, T., Berthet, P., Mennes, M.J.J., Andreassen, O.A., Westlye, L.T., Beckmann, C.F., Marquand, A.F., Kia, S.M., Huijsdens, H., Rutherford, S.E.R., Boer, A.A.A. de, Dinga, R., Wolfers, T., Berthet, P., Mennes, M.J.J., Andreassen, O.A., Westlye, L.T., Beckmann, C.F., and Marquand, A.F.

Abstract

Contains fulltext : 287171.pdf (Publisher’s version ) (Open Access), Clinical neuroimaging data availability has grown substantially in the last decade, providing the potential for studying heterogeneity in clinical cohorts on a previously unprecedented scale. Normative modeling is an emerging statistical tool for dissecting heterogeneity in complex brain disorders. However, its application remains technically challenging due to medical data privacy issues and difficulties in dealing with nuisance variation, such as the variability in the image acquisition process. Here, we approach the problem of estimating a reference normative model across a massive population using a massive multi-center neuroimaging dataset. To this end, we introduce a federated probabilistic framework using hierarchical Bayesian regression (HBR) to complete the life-cycle of normative modeling. The proposed model provides the possibilities to learn, update, and adapt the model parameters on decentralized neuroimaging data. Our experimental results confirm the superiority of HBR in deriving more accurate normative ranges on large multi-site neuroimaging datasets compared to the current standard methods. In addition, our approach provides the possibility to recalibrate and reuse the learned model on local datasets and even on datasets with very small sample sizes. The proposed method will facilitate applications of normative modeling as a medical tool for screening the biological deviations in individuals affected by complex illnesses such as mental disorders.

Published
2022

23. Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders

Author

Hettwer, M.D., Larivière, S., Park, B.Y., Heuvel, O.A. van den, Schmaal, L., Andreassen, O.A., Hoogman, M., Buitelaar, J.K., Rooij, D. van, Franke, B., Eickhoff, S.B., Valk, S.L., Hettwer, M.D., Larivière, S., Park, B.Y., Heuvel, O.A. van den, Schmaal, L., Andreassen, O.A., Hoogman, M., Buitelaar, J.K., Rooij, D. van, Franke, B., Eickhoff, S.B., and Valk, S.L.

Abstract

Contains fulltext : 286067.pdf (Publisher’s version ) (Open Access)

Published
2022

24. In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group

Author

Haukvik, U.K., Gurholt, T.P., Nerland, S., Elvsåshagen, T., Akudjedu, T.N., Alda, M., Alnaes, D., Alonso-Lana, S., Bauer, J., Baune, B.T., Benedetti, F. De, Berk, M., Bettella, F., Bøen, E., Bonnín, C.M., Brambilla, P., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Erp, T.G. van, Fatjó-Vilas, M., Foley, S.F., Förster, K., Fullerton, J.M., Goikolea, J.M., Grotegerd, D., Gruber, O., Haarman, B.C.M., Haatveit, B., Hajek, T., Hallahan, B., Harris, M., Hawkins, E.L., Howells, F.M., Hülsmann, C., Jahanshad, N., Jørgensen, K.N., Kircher, T., Krämer, B., Krug, A., Kuplicki, R., Lagerberg, T.V., Lancaster, T.M., Lenroot, R.K., Lonning, V., López-Jaramillo, C., Malt, U.F., McDonald, C., McIntosh, A.M., McPhilemy, G., Meer, D. van der, Melle, I., Melloni, E.M.T., Mitchell, P.B., Nabulsi, L., Nenadić, I., Oertel, V., Oldani, L., Opel, N., Otaduy, M.C.G., Overs, B.J., Pineda-Zapata, J.A., Pomarol-Clotet, E., Radua, J., Rauer, L., Redlich, R., Repple, J., Rive, M.M., Roberts, G., Ruhe, H.G., Salminen, L.E., Salvador, R., Sarró, S., Savitz, J., Schene, A.H., Sim, K., Soeiro-de-Souza, M.G., Stäblein, M., Stein, D.J., Stein, F., Tamnes, C.K., Temmingh, H.S., Thomopoulos, S.I., Veltman, D.J., Vieta, E., Waltemate, L., Westlye, L.T., Whalley, H.C., Sämann, P.G., Thompson, P.M., Ching, C.R., Andreassen, O.A., Agartz, I., Haukvik, U.K., Gurholt, T.P., Nerland, S., Elvsåshagen, T., Akudjedu, T.N., Alda, M., Alnaes, D., Alonso-Lana, S., Bauer, J., Baune, B.T., Benedetti, F. De, Berk, M., Bettella, F., Bøen, E., Bonnín, C.M., Brambilla, P., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Erp, T.G. van, Fatjó-Vilas, M., Foley, S.F., Förster, K., Fullerton, J.M., Goikolea, J.M., Grotegerd, D., Gruber, O., Haarman, B.C.M., Haatveit, B., Hajek, T., Hallahan, B., Harris, M., Hawkins, E.L., Howells, F.M., Hülsmann, C., Jahanshad, N., Jørgensen, K.N., Kircher, T., Krämer, B., Krug, A., Kuplicki, R., Lagerberg, T.V., Lancaster, T.M., Lenroot, R.K., Lonning, V., López-Jaramillo, C., Malt, U.F., McDonald, C., McIntosh, A.M., McPhilemy, G., Meer, D. van der, Melle, I., Melloni, E.M.T., Mitchell, P.B., Nabulsi, L., Nenadić, I., Oertel, V., Oldani, L., Opel, N., Otaduy, M.C.G., Overs, B.J., Pineda-Zapata, J.A., Pomarol-Clotet, E., Radua, J., Rauer, L., Redlich, R., Repple, J., Rive, M.M., Roberts, G., Ruhe, H.G., Salminen, L.E., Salvador, R., Sarró, S., Savitz, J., Schene, A.H., Sim, K., Soeiro-de-Souza, M.G., Stäblein, M., Stein, D.J., Stein, F., Tamnes, C.K., Temmingh, H.S., Thomopoulos, S.I., Veltman, D.J., Vieta, E., Waltemate, L., Westlye, L.T., Whalley, H.C., Sämann, P.G., Thompson, P.M., Ching, C.R., Andreassen, O.A., and Agartz, I.

Abstract

Contains fulltext : 252169.pdf (Publisher’s version ) (Open Access), The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Published
2022

25. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Author

Ching, C.R., Hibar, D.P., Gurholt, T.P., Nunes, A., Thomopoulos, S.I., Abé, C., Agartz, I., Brouwer, R.M., Cannon, D.M., Zwarte, S.M.C. de, Eyler, L.T., Favre, P., Hajek, T., Haukvik, U.K., Houenou, J., Landén, M., Lett, T.A., McDonald, C., Nabulsi, L., Patel, Y., Pauling, M.E., Paus, T., Radua, J., Soeiro-de-Souza, M.G., Tronchin, G., Haren, N.E.M. van, Vieta, E., Walter, H., Zeng, L.L., Alda, M., Almeida, J., Alnaes, D., Alonso-Lana, S., Altimus, C., Bauer, M, Baune, B.T., Bearden, C.E., Bellani, M., Benedetti, F. De, Berk, M., Bilderbeck, A.C., Blumberg, H.P., Bøen, E., Bollettini, I., Bonnin, C. Del Mar, Brambilla, P., Canales-Rodríguez, E.J., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Dima, D., Duchesnay, É., Elvsåshagen, T., Fears, S.C., Frangou, S., Fullerton, J.M., Glahn, D.C., Goikolea, J.M., Green, M.J., Grotegerd, D., Gruber, O., Haarman, B.C.M., Henry, C., Howells, F.M., Ives-Deliperi, V., Jansen, Andreas, Kircher, T.T.J., Knöchel, C., Kramer, B., Lafer, B., López-Jaramillo, C., Machado-Vieira, R., MacIntosh, B.J., Melloni, E.M.T., Mitchell, P.B., Nenadic, I., Nery, F., Nugent, A.C., Oertel, V., Ophoff, R.A., Ota, M., Overs, B.J., Pham, D.L., Phillips, M.L., Pineda-Zapata, J.A., Poletti, S., Polosan, M., Pomarol-Clotet, E., Pouchon, A., Quidé, Y., Rive, M.M., Roberts, G., Ruhe, H.G., Salvador, R., Sarró, S., Satterthwaite, T.D., Schene, A.H., Sim, K., Thompson, P.M., Andreassen, O.A., Ching, C.R., Hibar, D.P., Gurholt, T.P., Nunes, A., Thomopoulos, S.I., Abé, C., Agartz, I., Brouwer, R.M., Cannon, D.M., Zwarte, S.M.C. de, Eyler, L.T., Favre, P., Hajek, T., Haukvik, U.K., Houenou, J., Landén, M., Lett, T.A., McDonald, C., Nabulsi, L., Patel, Y., Pauling, M.E., Paus, T., Radua, J., Soeiro-de-Souza, M.G., Tronchin, G., Haren, N.E.M. van, Vieta, E., Walter, H., Zeng, L.L., Alda, M., Almeida, J., Alnaes, D., Alonso-Lana, S., Altimus, C., Bauer, M, Baune, B.T., Bearden, C.E., Bellani, M., Benedetti, F. De, Berk, M., Bilderbeck, A.C., Blumberg, H.P., Bøen, E., Bollettini, I., Bonnin, C. Del Mar, Brambilla, P., Canales-Rodríguez, E.J., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Dima, D., Duchesnay, É., Elvsåshagen, T., Fears, S.C., Frangou, S., Fullerton, J.M., Glahn, D.C., Goikolea, J.M., Green, M.J., Grotegerd, D., Gruber, O., Haarman, B.C.M., Henry, C., Howells, F.M., Ives-Deliperi, V., Jansen, Andreas, Kircher, T.T.J., Knöchel, C., Kramer, B., Lafer, B., López-Jaramillo, C., Machado-Vieira, R., MacIntosh, B.J., Melloni, E.M.T., Mitchell, P.B., Nenadic, I., Nery, F., Nugent, A.C., Oertel, V., Ophoff, R.A., Ota, M., Overs, B.J., Pham, D.L., Phillips, M.L., Pineda-Zapata, J.A., Poletti, S., Polosan, M., Pomarol-Clotet, E., Pouchon, A., Quidé, Y., Rive, M.M., Roberts, G., Ruhe, H.G., Salvador, R., Sarró, S., Satterthwaite, T.D., Schene, A.H., Sim, K., Thompson, P.M., and Andreassen, O.A.

Abstract

Contains fulltext : 252204.pdf (Publisher’s version ) (Open Access), MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.

Published
2022

26. Deep neural networks learn general and clinically relevant representations of the ageing brain

Author

Leonardsen, E.H., Peng, H., Kaufmann, T., Agartz, I., Andreassen, O.A., Celius, E.G., Espeseth, T., Harbo, H.F., Høgestøl, E.A., Lange, Ann-Marie de, Marquand, A.F., Vidal-Piñeiro, D., Roe, J.M., Selbæk, G., Sørensen, Ø., Smith, S.M., Westlye, L.T., Wolfers, T., Wang, Y., Leonardsen, E.H., Peng, H., Kaufmann, T., Agartz, I., Andreassen, O.A., Celius, E.G., Espeseth, T., Harbo, H.F., Høgestøl, E.A., Lange, Ann-Marie de, Marquand, A.F., Vidal-Piñeiro, D., Roe, J.M., Selbæk, G., Sørensen, Ø., Smith, S.M., Westlye, L.T., Wolfers, T., and Wang, Y.

Abstract

Contains fulltext : 251344.pdf (Publisher’s version ) (Open Access), The discrepancy between chronological age and the apparent age of the brain based on neuroimaging data - the brain age delta - has emerged as a reliable marker of brain health. With an increasing wealth of data, approaches to tackle heterogeneity in data acquisition are vital. To this end, we compiled raw structural magnetic resonance images into one of the largest and most diverse datasets assembled (n=53542), and trained convolutional neural networks (CNNs) to predict age. We achieved state-of-the-art performance on unseen data from unknown scanners (n=2553), and showed that higher brain age delta is associated with diabetes, alcohol intake and smoking. Using transfer learning, the intermediate representations learned by our model complemented and partly outperformed brain age delta in predicting common brain disorders. Our work shows we can achieve generalizable and biologically plausible brain age predictions using CNNs trained on heterogeneous datasets, and transfer them to clinical use cases.

Published
2022

27. Multiscale neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

Author

Park, B.Y., Kebets, V., Larivière, S., Hettwer, M.D., Paquola, C., Rooij, D. van, Buitelaar, J.K., Franke, B., Hoogman, M., Schmaal, L., Veltman, D.J., Heuvel, O.A. van den, Stein, D.J., Andreassen, O.A., Ching, C.R., Turner, J.A., Erp, T.G. van, Evans, A.C., Dagher, A., Thomopoulos, S.I., Thompson, P.M., Valk, S.L., Kirschner, M., Bernhardt, B.C., Park, B.Y., Kebets, V., Larivière, S., Hettwer, M.D., Paquola, C., Rooij, D. van, Buitelaar, J.K., Franke, B., Hoogman, M., Schmaal, L., Veltman, D.J., Heuvel, O.A. van den, Stein, D.J., Andreassen, O.A., Ching, C.R., Turner, J.A., Erp, T.G. van, Evans, A.C., Dagher, A., Thomopoulos, S.I., Thompson, P.M., Valk, S.L., Kirschner, M., and Bernhardt, B.C.

Abstract

Contains fulltext : 281801.pdf (Publisher’s version ) (Open Access), It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we carried out a multiscale neural contextualization of shared alterations of cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression disorder, obsessive-compulsive disorder, bipolar disorder, and schizophrenia). Our framework cross-referenced shared morphological anomalies with respect to cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we identified a cortex-wide dimension of morphological changes that described a sensory-fugal pattern, with paralimbic regions showing the most consistent alterations across conditions. The shared disease dimension was closely related to cortical gradients of microstructure as well as neurotransmitter axes, specifically cortex-wide variations in serotonin and dopamine. Multiple sensitivity analyses confirmed robustness with respect to slight variations in analytical choices. Our findings embed shared effects of common psychiatric conditions on brain structure in multiple scales of brain organization, and may provide insights into neural mechanisms of transdiagnostic vulnerability.

Published
2022

28. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author

Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A., Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.-M., Landén, M., Landrø, N.I., Lawrie, S., Lebedeva, I., Luna, B., Lundervold, A.J., MacMaster, F.P., Maglanoc, L.A., Mathalon, D.H., McDonald, C., McIntosh, A., Meinert, S., Michie, P.T., Mitchell, P., Moreno-Alcázar, A., Mowry, B., Muratori, F., Nabulsi, L., Nenadić, I., O'Gorman Tuura, R., Oosterlaan, J., Overs, B., Pantelis, C., Parellada, M., Pariente, J.C., Pauli, P., Pergola, G., Piarulli, F.M., Picon, F., Piras, F., Pomarol-Clotet, E., Pretus, C., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Reif, A., Retico, A., Roberts, G., Rossell, S., Rovaris, D.L., Rubia, K., Sacchet, M., Salavert, J., Salvador, R., Sarró, S., Sawa, A., Schall, U., Scott, R., Selvaggi, P., Silk, T., Sim, K., Skoch, A., Spalletta, G., Spaniel, F., Stein, D.J., Steinsträter, O., Stolicyn, A., Takayanagi, Y., Tamm, L., Tavares, M., Teumer, A., Thiel, K., Thomopoulos, S.I., Tomecek, D., Tomyshev, A.S., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Rheenen, T., Vazquez-Bourgón, J., Vernooij, M.W., Vieta, E., Vilarroya, O., Weickert, C., Weickert, T., Westlye, L.T., Whalley, H., Willinger, D., Winter, A., Wittfeld, K., Yang, T.T., Yoncheva, Y., Zijlmans, J.L., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J., Ching, C.R.K., Andreassen, O.A., Pozzi, E., Veltman, D., Schmaal, L., van Erp, T.G.M., Turner, J., Castellanos, F.X., Pausova, Z., Thompson, P., Paus, T., Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A., Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.-M., Landén, M., Landrø, N.I., Lawrie, S., Lebedeva, I., Luna, B., Lundervold, A.J., MacMaster, F.P., Maglanoc, L.A., Mathalon, D.H., McDonald, C., McIntosh, A., Meinert, S., Michie, P.T., Mitchell, P., Moreno-Alcázar, A., Mowry, B., Muratori, F., Nabulsi, L., Nenadić, I., O'Gorman Tuura, R., Oosterlaan, J., Overs, B., Pantelis, C., Parellada, M., Pariente, J.C., Pauli, P., Pergola, G., Piarulli, F.M., Picon, F., Piras, F., Pomarol-Clotet, E., Pretus, C., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Reif, A., Retico, A., Roberts, G., Rossell, S., Rovaris, D.L., Rubia, K., Sacchet, M., Salavert, J., Salvador, R., Sarró, S., Sawa, A., Schall, U., Scott, R., Selvaggi, P., Silk, T., Sim, K., Skoch, A., Spalletta, G., Spaniel, F., Stein, D.J., Steinsträter, O., Stolicyn, A., Takayanagi, Y., Tamm, L., Tavares, M., Teumer, A., Thiel, K., Thomopoulos, S.I., Tomecek, D., Tomyshev, A.S., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Rheenen, T., Vazquez-Bourgón, J., Vernooij, M.W., Vieta, E., Vilarroya, O., Weickert, C., Weickert, T., Westlye, L.T., Whalley, H., Willinger, D., Winter, A., Wittfeld, K., Yang, T.T., Yoncheva, Y., Zijlmans, J.L., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J., Ching, C.R.K., Andreassen, O.A., Pozzi, E., Veltman, D., Schmaal, L., van Erp, T.G.M., Turner, J., Castellanos, F.X., Pausova, Z., Thompson, P., and Paus, T.

Abstract

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t

Published
2022
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29. Brain based BMIgap as a new tool to correlate obesity and neural alterations – a multicohort study

Author

Khuntia, A., Paul, R., Andreassen, O.A., Degenhard, F., Eils, R., Erdmann, J., Herrmann, C., Hofmann-Apitius, M., Kaufmann, T., Kodamullil, A.T., Mucha, S., Nöthen, M.M., Pedersen, M.L., Quintero, A., Schunkert, H., Sharma, A., Tost, H., Westlye, L.T., Zhang, Y., Kambeitz, J., Salokangas, R.K.R., Hietala, J., Bertolino, A., Brambilla, P., Upthegrove, R., Wood, S.J., Lencer, R., Borgwardt, S., Meyer-Lindenberg, A., Meisenzahl, E., Falkai, P., Schwarz, E., and Koutsouleris, N.

Published
2022
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31. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author

Sønderby, I.E., Ching, CRK, Thomopoulos, S.I., van der Meer, D., Sun, D., Villalon-Reina, J.E., Agartz, I., Amunts, K., Arango, C., Armstrong, N.J., Ayesa-Arriola, R., Bakker, G., Bassett, A.S., Boomsma, D.I., Bülow, R., Butcher, N.J., Calhoun, V.D., Caspers, S., Chow, EWC, Cichon, S., Ciufolini, S., Craig, M.C., Crespo-Facorro, B., Cunningham, A.C., Dale, A.M., Dazzan, P., de Zubicaray, G.I., Djurovic, S., Doherty, J.L., Donohoe, G., Draganski, B., Durdle, C.A., Ehrlich, S., Emanuel, B.S., Espeseth, T., Fisher, S.E., Ge, T., Glahn, D.C., Grabe, H.J., Gur, R.E., Gutman, B.A., Haavik, J., Håberg, A.K., Hansen, L.A., Hashimoto, R., Hibar, D.P., Holmes, A.J., Hottenga, J.J., Hulshoff Pol, H.E., Jalbrzikowski, M., Knowles, EEM, Kushan, L., Linden, DEJ, Liu, J., Lundervold, A.J., Martin-Brevet, S., Martínez, K., Mather, K.A., Mathias, S.R., McDonald-McGinn, D.M., McRae, A.F., Medland, S.E., Moberget, T., Modenato, C., Monereo Sánchez, J., Moreau, C.A., Mühleisen, T.W., Paus, T., Pausova, Z., Prieto, C., Ragothaman, A., Reinbold, C.S., Reis Marques, T., Repetto, G.M., Reymond, A., Roalf, D.R., Rodriguez-Herreros, B., Rucker, J.J., Sachdev, P.S., Schmitt, J.E., Schofield, P.R., Silva, A.I., Stefansson, H., Stein, D.J., Tamnes, C.K., Tordesillas-Gutiérrez, D., Ulfarsson, M.O., Vajdi, A., van 't Ent, D., van den Bree, MBM, Vassos, E., Vázquez-Bourgon, J., Vila-Rodriguez, F., Walters, G.B., Wen, W., Westlye, L.T., Wittfeld, K., Zackai, E.H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Bearden, C.E., Andreassen, O.A., ENIGMA-CNV Working Group, ENIGMA 22q11.2 Deletion Syndrome Working Group, Bernard, M., Blackburn, N.B., Bøen, R., de Geus, E., de Zwarte, SMC, Forti, M.D., Frei, O., Fukunaga, M., Hehir-Kwa, J.Y., Hillegers, MHJ, Hoffmann, P., Homuth, G., Jahanshad, N., Koops, S., Kumar, K., Kikuchi, M., Le Hellard, S., Leu, C., Murray, R.M., Naerland, T., Nyberg, L., Ophoff, R.A., Pike, G.B., Sando, S.B., Shin, J., Shumskaya, E., Sisodiya, S.M., Steen, V.M., Teumer, A., Uhlmann, A., Wright, M.J., Antshel, K.M., Campbell, L.E., Crossley, N.A., Crowley, T.B., Daly, E., Fiksinski, A.M., Forsyth, J.K., Fremont, W., Goodrich-Hunsaker, N.J., Gudbrandsen, M., Jonas, R.K., Kates, W.R., Lin, A., McCabe, K.L., Moss, H., Murphy, D.G., Murphy, K.C., Owen, M.J., Ruparel, K., Simon, T.J., van Amelsvoort, T., and Vorstman, JAS

Subjects
brain structural imaging, copy number variant, diffusion tensor imaging, evolution, genetics-first approach, neurodevelopmental disorders, psychiatric disorders
Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

Published
2022

32. New insights into the genetic etiology of Alzheimer's disease and related dementias

Author

Bellenguez, C. Küçükali, F. Jansen, I.E. Kleineidam, L. Moreno-Grau, S. Amin, N. Naj, A.C. Campos-Martin, R. Grenier-Boley, B. Andrade, V. Holmans, P.A. Boland, A. Damotte, V. van der Lee, S.J. Costa, M.R. Kuulasmaa, T. Yang, Q. de Rojas, I. Bis, J.C. Yaqub, A. Prokic, I. Chapuis, J. Ahmad, S. Giedraitis, V. Aarsland, D. Garcia-Gonzalez, P. Abdelnour, C. Alarcón-Martín, E. Alcolea, D. Alegret, M. Alvarez, I. Álvarez, V. Armstrong, N.J. Tsolaki, A. Antúnez, C. Appollonio, I. Arcaro, M. Archetti, S. Pastor, A.A. Arosio, B. Athanasiu, L. Bailly, H. Banaj, N. Baquero, M. Barral, S. Beiser, A. Pastor, A.B. Below, J.E. Benchek, P. Benussi, L. Berr, C. Besse, C. Bessi, V. Binetti, G. Bizarro, A. Blesa, R. Boada, M. Boerwinkle, E. Borroni, B. Boschi, S. Bossù, P. Bråthen, G. Bressler, J. Bresner, C. Brodaty, H. Brookes, K.J. Brusco, L.I. Buiza-Rueda, D. Bûrger, K. Burholt, V. Bush, W.S. Calero, M. Cantwell, L.B. Chene, G. Chung, J. Cuccaro, M.L. Carracedo, Á. Cecchetti, R. Cervera-Carles, L. Charbonnier, C. Chen, H.-H. Chillotti, C. Ciccone, S. Claassen, J.A.H.R. Clark, C. Conti, E. Corma-Gómez, A. Costantini, E. Custodero, C. Daian, D. Dalmasso, M.C. Daniele, A. Dardiotis, E. Dartigues, J.-F. de Deyn, P.P. de Paiva Lopes, K. de Witte, L.D. Debette, S. Deckert, J. Del Ser, T. Denning, N. DeStefano, A. Dichgans, M. Diehl-Schmid, J. Diez-Fairen, M. Rossi, P.D. Djurovic, S. Duron, E. Düzel, E. Dufouil, C. Eiriksdottir, G. Engelborghs, S. Escott-Price, V. Espinosa, A. Ewers, M. Faber, K.M. Fabrizio, T. Nielsen, S.F. Fardo, D.W. Farotti, L. Fenoglio, C. Fernández-Fuertes, M. Ferrari, R. Ferreira, C.B. Ferri, E. Fin, B. Fischer, P. Fladby, T. Fließbach, K. Fongang, B. Fornage, M. Fortea, J. Foroud, T.M. Fostinelli, S. Fox, N.C. Franco-Macías, E. Bullido, M.J. Frank-García, A. Froelich, L. Fulton-Howard, B. Galimberti, D. García-Alberca, J.M. García-González, P. Garcia-Madrona, S. Garcia-Ribas, G. Ghidoni, R. Giegling, I. Giorgio, G. Goate, A.M. Goldhardt, O. Gomez-Fonseca, D. González-Pérez, A. Graff, C. Grande, G. Green, E. Grimmer, T. Grünblatt, E. Grunin, M. Gudnason, V. Guetta-Baranes, T. Haapasalo, A. Hadjigeorgiou, G. Haines, J.L. Hamilton-Nelson, K.L. Hampel, H. Hanon, O. Hardy, J. Hartmann, A.M. Hausner, L. Harwood, J. Heilmann-Heimbach, S. Helisalmi, S. Heneka, M.T. Hernández, I. Herrmann, M.J. Hoffmann, P. Holmes, C. Holstege, H. Vilas, R.H. Hulsman, M. Humphrey, J. Biessels, G.J. Jian, X. Johansson, C. Jun, G.R. Kastumata, Y. Kauwe, J. Kehoe, P.G. Kilander, L. Ståhlbom, A.K. Kivipelto, M. Koivisto, A. Kornhuber, J. Kosmidis, M.H. Kukull, W.A. Kuksa, P.P. Kunkle, B.W. Kuzma, A.B. Lage, C. Laukka, E.J. Launer, L. Lauria, A. Lee, C.-Y. Lehtisalo, J. Lerch, O. Lleó, A. Longstreth, W., Jr Lopez, O. de Munain, A.L. Love, S. Löwemark, M. Luckcuck, L. Lunetta, K.L. Ma, Y. Macías, J. MacLeod, C.A. Maier, W. Mangialasche, F. Spallazzi, M. Marquié, M. Marshall, R. Martin, E.R. Montes, A.M. Rodríguez, C.M. Masullo, C. Mayeux, R. Mead, S. Mecocci, P. Medina, M. Meggy, A. Mehrabian, S. Mendoza, S. Menéndez-González, M. Mir, P. Moebus, S. Mol, M. Molina-Porcel, L. Montrreal, L. Morelli, L. Moreno, F. Morgan, K. Mosley, T. Nöthen, M.M. Muchnik, C. Mukherjee, S. Nacmias, B. Ngandu, T. Nicolas, G. Nordestgaard, B.G. Olaso, R. Orellana, A. Orsini, M. Ortega, G. Padovani, A. Paolo, C. Papenberg, G. Parnetti, L. Pasquier, F. Pastor, P. Peloso, G. Pérez-Cordón, A. Pérez-Tur, J. Pericard, P. Peters, O. Pijnenburg, Y.A.L. Pineda, J.A. Piñol-Ripoll, G. Pisanu, C. Polak, T. Popp, J. Posthuma, D. Priller, J. Puerta, R. Quenez, O. Quintela, I. Thomassen, J.Q. Rábano, A. Rainero, I. Rajabli, F. Ramakers, I. Real, L.M. Reinders, M.J.T. Reitz, C. Reyes-Dumeyer, D. Ridge, P. Riedel-Heller, S. Riederer, P. Roberto, N. Rodriguez-Rodriguez, E. Rongve, A. Allende, I.R. Rosende-Roca, M. Royo, J.L. Rubino, E. Rujescu, D. Sáez, M.E. Sakka, P. Saltvedt, I. Sanabria, Á. Sánchez-Arjona, M.B. Sanchez-Garcia, F. Juan, P.S. Sánchez-Valle, R. Sando, S.B. Sarnowski, C. Satizabal, C.L. Scamosci, M. Scarmeas, N. Scarpini, E. Scheltens, P. Scherbaum, N. Scherer, M. Schmid, M. Schneider, A. Schott, J.M. Selbæk, G. Seripa, D. Serrano, M. Sha, J. Shadrin, A.A. Skrobot, O. Slifer, S. Snijders, G.J.L. Soininen, H. Solfrizzi, V. Solomon, A. Song, Y. Sorbi, S. Sotolongo-Grau, O. Spalletta, G. Spottke, A. Squassina, A. Stordal, E. Tartan, J.P. Tárraga, L. Tesí, N. Thalamuthu, A. Thomas, T. Tosto, G. Traykov, L. Tremolizzo, L. Tybjærg-Hansen, A. Uitterlinden, A. Ullgren, A. Ulstein, I. Valero, S. Valladares, O. Broeckhoven, C.V. Vance, J. Vardarajan, B.N. van der Lugt, A. Dongen, J.V. van Rooij, J. van Swieten, J. Vandenberghe, R. Verhey, F. Vidal, J.-S. Vogelgsang, J. Vyhnalek, M. Wagner, M. Wallon, D. Wang, L.-S. Wang, R. Weinhold, L. Wiltfang, J. Windle, G. Woods, B. Yannakoulia, M. Zare, H. Zhao, Y. Zhang, X. Zhu, C. Zulaica, M. Farrer, L.A. Psaty, B.M. Ghanbari, M. Raj, T. Sachdev, P. Mather, K. Jessen, F. Ikram, M.A. de Mendonça, A. Hort, J. Tsolaki, M. Pericak-Vance, M.A. Amouyel, P. Williams, J. Frikke-Schmidt, R. Clarimon, J. Deleuze, J.-F. Rossi, G. Seshadri, S. Andreassen, O.A. Ingelsson, M. Hiltunen, M. Sleegers, K. Schellenberg, G.D. van Duijn, C.M. Sims, R. van der Flier, W.M. Ruiz, A. Ramirez, A. Lambert, J.-C. EADB GR@ACE DEGESCO EADI GERAD Demgene FinnGen ADGC CHARGE

Abstract

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022. The Author(s).

Published
2022

37. 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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40. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Mullins, N. Forstner, A.J. O’Connell, K.S. Coombes, B. Coleman, J.R.I. Qiao, Z. Als, T.D. Bigdeli, T.B. Børte, S. Bryois, J. Charney, A.W. Drange, O.K. Gandal, M.J. Hagenaars, S.P. Ikeda, M. Kamitaki, N. Kim, M. Krebs, K. Panagiotaropoulou, G. Schilder, B.M. Sloofman, L.G. Steinberg, S. Trubetskoy, V. Winsvold, B.S. Won, H.-H. Abramova, L. Adorjan, K. Agerbo, E. Al Eissa, M. Albani, D. Alliey-Rodriguez, N. Anjorin, A. Antilla, V. Antoniou, A. Awasthi, S. Baek, J.H. Bækvad-Hansen, M. Bass, N. Bauer, M. Beins, E.C. Bergen, S.E. Birner, A. Bøcker Pedersen, C. Bøen, E. Boks, M.P. Bosch, R. Brum, M. Brumpton, B.M. Brunkhorst-Kanaan, N. Budde, M. Bybjerg-Grauholm, J. Byerley, W. Cairns, M. Casas, M. Cervantes, P. Clarke, T.-K. Cruceanu, C. Cuellar-Barboza, A. Cunningham, J. Curtis, D. Czerski, P.M. Dale, A.M. Dalkner, N. David, F.S. Degenhardt, F. Djurovic, S. Dobbyn, A.L. Douzenis, A. Elvsåshagen, T. Escott-Price, V. Ferrier, I.N. Fiorentino, A. Foroud, T.M. Forty, L. Frank, J. Frei, O. Freimer, N.B. Frisén, L. Gade, K. Garnham, J. Gelernter, J. Giørtz Pedersen, M. Gizer, I.R. Gordon, S.D. Gordon-Smith, K. Greenwood, T.A. Grove, J. Guzman-Parra, J. Ha, K. Haraldsson, M. Hautzinger, M. Heilbronner, U. Hellgren, D. Herms, S. Hoffmann, P. Holmans, P.A. Huckins, L. Jamain, S. Johnson, J.S. Kalman, J.L. Kamatani, Y. Kennedy, J.L. Kittel-Schneider, S. Knowles, J.A. Kogevinas, M. Koromina, M. Kranz, T.M. Kranzler, H.R. Kubo, M. Kupka, R. Kushner, S.A. Lavebratt, C. Lawrence, J. Leber, M. Lee, H.-J. Lee, P.H. Levy, S.E. Lewis, C. Liao, C. Lucae, S. Lundberg, M. MacIntyre, D.J. Magnusson, S.H. Maier, W. Maihofer, A. Malaspina, D. Maratou, E. Martinsson, L. Mattheisen, M. McCarroll, S.A. McGregor, N.W. McGuffin, P. McKay, J.D. Medeiros, H. Medland, S.E. Millischer, V. Montgomery, G.W. Moran, J.L. Morris, D.W. Mühleisen, T.W. O’Brien, N. O’Donovan, C. Olde Loohuis, L.M. Oruc, L. Papiol, S. Pardiñas, A.F. Perry, A. Pfennig, A. Porichi, E. Potash, J.B. Quested, D. Raj, T. Rapaport, M.H. DePaulo, J.R. Regeer, E.J. Rice, J.P. Rivas, F. Rivera, M. Roth, J. Roussos, P. Ruderfer, D.M. Sánchez-Mora, C. Schulte, E.C. Senner, F. Sharp, S. Shilling, P.D. Sigurdsson, E. Sirignano, L. Slaney, C. Smeland, O.B. Smith, D.J. Sobell, J.L. Søholm Hansen, C. Soler Artigas, M. Spijker, A.T. Stein, D.J. Strauss, J.S. Świątkowska, B. Terao, C. Thorgeirsson, T.E. Toma, C. Tooney, P. Tsermpini, E.-E. Vawter, M.P. Vedder, H. Walters, J.T.R. Witt, S.H. Xi, S. Xu, W. Yang, J.M.K. Young, A.H. Young, H. Zandi, P.P. Zhou, H. Zillich, L. Adolfsson, R. Agartz, I. Alda, M. Alfredsson, L. Babadjanova, G. Backlund, L. Baune, B.T. Bellivier, F. Bengesser, S. Berrettini, W.H. Blackwood, D.H.R. Boehnke, M. Børglum, A.D. Breen, G. Carr, V.J. Catts, S. Corvin, A. Craddock, N. Dannlowski, U. Dikeos, D. Esko, T. Etain, B. Ferentinos, P. Frye, M. Fullerton, J.M. Gawlik, M. Gershon, E.S. Goes, F.S. Green, M.J. Grigoroiu-Serbanescu, M. Hauser, J. Henskens, F. Hillert, J. Hong, K.S. Hougaard, D.M. Hultman, C.M. Hveem, K. Iwata, N. Jablensky, A.V. Jones, I. Jones, L.A. Kahn, R.S. Kelsoe, J.R. Kirov, G. Landén, M. Leboyer, M. Lewis, C.M. Li, Q.S. Lissowska, J. Lochner, C. Loughland, C. Martin, N.G. Mathews, C.A. Mayoral, F. McElroy, S.L. McIntosh, A.M. McMahon, F.J. Melle, I. Michie, P. Milani, L. Mitchell, P.B. Morken, G. Mors, O. Mortensen, P.B. Mowry, B. Müller-Myhsok, B. Myers, R.M. Neale, B.M. Nievergelt, C.M. Nordentoft, M. Nöthen, M.M. O’Donovan, M.C. Oedegaard, K.J. Olsson, T. Owen, M.J. Paciga, S.A. Pantelis, C. Pato, C. Pato, M.T. Patrinos, G.P. Perlis, R.H. Posthuma, D. Ramos-Quiroga, J.A. Reif, A. Reininghaus, E.Z. Ribasés, M. Rietschel, M. Ripke, S. Rouleau, G.A. Saito, T. Schall, U. Schalling, M. Schofield, P.R. Schulze, T.G. Scott, L.J. Scott, R.J. Serretti, A. Shannon Weickert, C. Smoller, J.W. Stefansson, H. Stefansson, K. Stordal, E. Streit, F. Sullivan, P.F. Turecki, G. Vaaler, A.E. Vieta, E. Vincent, J.B. Waldman, I.D. Weickert, T.W. Werge, T. Wray, N.R. Zwart, J.-A. Biernacka, J.M. Nurnberger, J.I. Cichon, S. Edenberg, H.J. Stahl, E.A. McQuillin, A. Di Florio, A. Ophoff, R.A. Andreassen, O.A. HUNT All-In Psychiatry

Abstract

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2021

41. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. Deckert, J. Buerger, K. Morgan, K. Fließbach, K. Sleegers, K. Molina-Porcel, L. Kilander, L. Weinhold, L. Farrer, L.A. Wang, L.-S. Kleineidam, L. Farotti, L. Parnetti, L. Tremolizzo, L. Hausner, L. Benussi, L. Froelich, L. Ikram, M.A. Deniz-Naranjo, M.C. Tsolaki, M. Rosende-Roca, M. Löwenmark, M. Hulsman, M. Spallazzi, M. Pericak-Vance, M.A. Esiri, M. Bernal Sánchez-Arjona, M. Dalmasso, M.C. Martínez-Larrad, M.T. Arcaro, M. Nöthen, M.M. Fernández-Fuertes, M. Dichgans, M. Ingelsson, M. Herrmann, M.J. Scherer, M. Vyhnalek, M. Kosmidis, M.H. Yannakoulia, M. Schmid, M. Ewers, M. Heneka, M.T. Wagner, M. Scamosci, M. Kivipelto, M. Hiltunen, M. Zulaica, M. Alegret, M. Fornage, M. Roberto, N. van Schoor, N.M. Seidu, N.M. Banaj, N. Armstrong, N.J. Scarmeas, N. Scherbaum, N. Goldhardt, O. Hanon, O. Peters, O. Skrobot, O.A. Quenez, O. Lerch, O. Bossù, P. Caffarra, P. Dionigi Rossi, P. Sakka, P. Hoffmann, P. Holmans, P.A. Fischer, P. Riederer, P. Yang, Q. Marshall, R. Kalaria, R.N. Mayeux, R. Vandenberghe, R. Cecchetti, R. Ghidoni, R. Frikke-Schmidt, R. Sorbi, S. Hägg, S. Engelborghs, S. Helisalmi, S. Botne Sando, S. Kern, S. Archetti, S. Boschi, S. Fostinelli, S. Gil, S. Mendoza, S. Mead, S. Ciccone, S. Djurovic, S. Heilmann-Heimbach, S. Riedel-Heller, S. Kuulasmaa, T. del Ser, T. Lebouvier, T. Polak, T. Ngandu, T. Grimmer, T. Bessi, V. Escott-Price, V. Giedraitis, V. Deramecourt, V. Maier, W. Jian, X. Pijnenburg, Y.A.L. Smith, A.D. Saenz, A. Bizzarro, A. Lauria, A. Vacca, A. Solomon, A. Anastasiou, A. Richardson, A. Boland, A. Koivisto, A. Daniele, A. Greco, A. Marianthi, A. McGuinness, B. Fin, B. Ferrari, C. Custodero, C. Ferrarese, C. Ingino, C. Mangone, C. Reyes Toso, C. Martínez, C. Cuesta, C. Muchnik, C. Joachim, C. Ortiz, C. Besse, C. Johansson, C. Zoia, C.P. Laske, C. Anastasiou, C. Palacio, D.L. Politis, D.G. Janowitz, D. Craig, D. Mann, D.M. Neary, D. Jürgen, D. Daian, D. Belezhanska, D. Kohler, E. Castaño, E.M. Koutsouraki, E. Chipi, E. De Roeck, E. Costantini, E. Vardy, E.R.L.C. Piras, F. Roveta, F. Piras, F. Prestia, F.A. Assogna, F. Salani, F. Sala, G. Lacidogna, G. Novack, G. Wilcock, G. Thonberg, H. Kölsch, H. Weber, H. Boecker, H. Etchepareborda, I. Piaceri, I. Tuomilehto, J. Lindström, J. Laczo, J. Johnston, J. Deleuze, J.-F. Harris, J. Schott, J.M. Priller, J. Bacha, J.I. Snowden, J. Lisso, J. Mihova, K.Y. Traykov, L. Morelli, L. Brusco, L.I. Rainer, M. Takalo, M. Bjerke, M. Del Zompo, M. Serpente, M. Sanchez Abalos, M. Rios, M. Peltonen, M. Herrman, M.J. Kosmidis, M.H. Kohler, M. Rojo, M. Jones, M. Orsini, M. Medel, N. Olivar, N. Fox, N.C. Salvadori, N. Hooper, N.M. Galeano, P. Solis, P. Bastiani, P. Mecocci, P. Passmore, P. Heun, R. Antikainen, R. Olaso, R. Perneczky, R. Germani, S. López-García, S. Love, S. Mehrabian, S. Bagnoli, S. Kochen, S. Andreoni, S. Teipel, S. Todd, S. Pickering-Brown, S. Natunen, T. Tegos, T. Laatikainen, T. Strandberg, T. Polvikoski, T.M. Matoska, V. Ciullo, V. Cores, V. Solfrizzi, V. Lisetti, V. Sevillano, Z. Abdelnour, C. Aguilera, N. Alarcon, E. Alegret, M. Benaque, A. Boada, M. Buendia, M. Cañabate, P. Carracedo, A. Corbatón-Anchuelo, A. Diego, S. Espinosa, A. Gailhajenet, A. Gil, S. Guitart, M. Hernández, I. Ibarria, M. Lafuente, A. Macias, J. Maroñas, O. Martín, E. Martínez, M.T. Marquié, M. Mauleón, A. Montrreal, L. Moreno-Grau, S. Moreno, M. Orellana, A. Ortega, G. Pancho, A. Pelejá, E. Pérez-Cordon, A. Pineda, J.A. Preckler, S. Quintela, I. Real, L.M. Rosende-Roca, M. Ruiz, A. Sáez, M.E. Sanabria, A. Serrano-Rios, M. Sotolongo-Grau, O. Tárraga, L. Valero, S. Vargas, L. Adarmes-Gómez, A.D. Alarcón-Martín, E. Alonso, M.D. Álvarez, I. Álvarez, V. Amer-Ferrer, G. Antequera, M. Antúnez, C. Baquero, M. Bernal, M. Blesa, R. Boada, M. Buiza-Rueda, D. Bullido, M.J. Burguera, J.A. Calero, M. Carrillo, F. Carrión-Claro, M. Casajeros, M.J. Clarimón, J. Cruz-Gamero, J.M. de Pancorbo, M.M. del Ser, T. Diez-Fairen, M. Escuela, R. Garrote-Espina, L. Fortea, J. Franco-Macías, E. Frank-García, A. García-Alberca, J.M. Garcia Madrona, S. Garcia-Ribas, G. Gómez-Garre, P. Hernández, I. Hevilla, S. Jesús, S. Labrador Espinosa, M.A. Lage, C. Legaz, A. Lleó, A. Lopez de Munain, A. López-García, S. Macias-García, D. Manzanares, S. Marín, M. Marín-Muñoz, J. Marín, T. Marquié, M. Martín Montes, A. Martínez, B. Martínez, C. Martínez, V. Martínez-Lage Álvarez, P. Medina, M. Mendioroz Iriarte, M. Mir, P. Molinuevo, J.L. Pastor, P. Pérez Tur, J. Periñán-Tocino, T. Pineda-Sanchez, R. Piñol-Ripoll, G. Rábano, A. Real de Asúa, D. Rodrigo, S. Rodríguez-Rodríguez, E. Royo, J.L. Ruiz, A. Sanchez del Valle Díaz, R. Sánchez-Juan, P. Sastre, I. Valero, S. Vicente, M.P. Vigo-Ortega, R. Vivancos, L. Macleod, C. McCracken, C. Brayne, C. Bresner, C. Grozeva, D. Bellou, E. Sommerville, E.W. Matthews, F. Leonenko, G. Menzies, G. Windle, G. Harwood, J. Phillips, J. Bennett, K. Luckuck, L. Clare, L. Woods, R. Saad, S. Burholt, V. Jansen, I.E. Rongve, A. Kehoe, P.G. Garcia-Ribas, G. Sánchez-Juan, P. Pastor, P. Pérez-Tur, J. Piñol-Ripoll, G. Lopez de Munain, A. García-Alberca, J.M. Bullido, M.J. Álvarez, V. Lleó, A. Real, L.M. Scheltens, P. Holstege, H. Marquié, M. Sáez, M.E. Carracedo, Á. Amouyel, P. Schellenberg, G.D. Williams, J. Seshadri, S. van Duijn, C.M. Mather, K.A. Sánchez-Valle, R. Serrano-Ríos, M. Orellana, A. Tárraga, L. Blennow, K. Huisman, M. Andreassen, O.A. Posthuma, D. Clarimón, J. Boada, M. van der Flier, W.M. Ramirez, A. Lambert, J.-C. van der Lee, S.J. Ruiz, A. EADB contributors The GR@ACE study group DEGESCO consortium IGAP (ADGC, CHARGE, EADI, GERAD) PGC-ALZ consortia

Abstract

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).

Published
2021

42. Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Author

Bauer, M. Glenn, T. Achtyes, E.D. Alda, M. Agaoglu, E. Altınbaş, K. Andreassen, O.A. Angelopoulos, E. Ardau, R. Vares, E.A. Aydin, M. Ayhan, Y. Baethge, C. Bauer, R. Baune, B.T. Balaban, C. Becerra-Palars, C. Behere, A.P. Behere, P.B. Belete, H. Belete, T. Belizario, G.O. Bellivier, F. Belmaker, R.H. Benedetti, F. Berk, M. Bersudsky, Y. Bicakci, Ş. Birabwa-Oketcho, H. Bjella, T.D. Brady, C. Cabrera, J. Cappucciati, M. Castro, A.M.P. Chen, W.-L. Cheung, E.Y.W. Chiesa, S. Crowe, M. Cuomo, A. Dallaspezia, S. Del Zompo, M. Desai, P. Dodd, S. Donix, M. Etain, B. Fagiolini, A. Fellendorf, F.T. Ferensztajn-Rochowiak, E. Fiedorowicz, J.G. Fountoulakis, K.N. Frye, M.A. Geoffroy, P.A. Gonzalez-Pinto, A. Gottlieb, J.F. Grof, P. Haarman, B.C.M. Harima, H. Hasse-Sousa, M. Henry, C. Høffding, L. Houenou, J. Imbesi, M. Isometsä, E.T. Ivkovic, M. Janno, S. Johnsen, S. Kapczinski, F. Karakatsoulis, G.N. Kardell, M. Kessing, L.V. Kim, S.J. König, B. Kot, T.L. Koval, M. Kunz, M. Lafer, B. Landén, M. Larsen, E.R. Lenger, M. Lewitzka, U. Licht, R.W. Lopez-Jaramillo, C. MacKenzie, A. Madsen, H.Ø. Madsen, S.A.K.A. Mahadevan, J. Mahardika, A. Manchia, M. Marsh, W. Martinez-Cengotitabengoa, M. Martiny, K. Mashima, Y. McLoughlin, D.M. Meesters, Y. Melle, I. Meza-Urzúa, F. Ming, M.Y. Monteith, S. Moorthy, M. Morken, G. Mosca, E. Mozzhegorov, A.A. Munoz, R. Mythri, S.V. Nacef, F. Nadella, R.K. Nakanotani, T. Nielsen, R.E. O‘Donovan, C. Omrani, A. Osher, Y. Ouali, U. Pantovic-Stefanovic, M. Pariwatcharakul, P. Petite, J. Pfennig, A. Ruiz, Y.P. Pilhatsch, M. Pinna, M. Pompili, M. Porter, R. Quiroz, D. Rabelo-da-Ponte, F.D. Ramesar, R. Rasgon, N. Ratta-apha, W. Ratzenhofer, M. Redahan, M. Reddy, M.S. Reif, A. Reininghaus, E.Z. Richards, J.G. Ritter, P. Rybakowski, J.K. Sathyaputri, L. Scippa, Â.M. Simhandl, C. Severus, E. Smith, D. Smith, J. Stackhouse, P.W., Jr. Stein, D.J. Stilwell, K. Strejilevich, S. Su, K.-P. Subramaniam, M. Sulaiman, A.H. Suominen, K. Tanra, A.J. Tatebayashi, Y. Teh, W.L. Tondo, L. Torrent, C. Tuinstra, D. Uchida, T. Vaaler, A.E. Veeh, J. Vieta, E. Viswanath, B. Yoldi-Negrete, M. Yalcinkaya, O.K. Young, A.H. Zgueb, Y. Whybrow, P.C.

Abstract

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed. © 2021, The Author(s).

Published
2021

43. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Author

Lam, M. Chen, C.-Y. Ge, T. Xia, Y. Hill, D.W. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Stahl, E.A. Huckins, L. Liewald, D.C. Djurovic, S. Melle, I. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Hartmann, A.M. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Koltai, D.C. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Smyrnis, N. Bilder, R.M. Freimer, N.B. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Huang, H. Liu, C. Malhotra, A.K. Lencz, T.

Abstract

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing. © 2021, The Author(s).

Published
2021

44. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, M.A. Johnson, E.C. Chou, Y.-L. Coleman, J.R.I. Thornton, L.M. Walters, R.K. Yilmaz, Z. Baker, J.H. Hübel, C. Gordon, S. Medland, S.E. Watson, H.J. Gaspar, H.A. Bryois, J. Hinney, A. Leppä, V.M. Mattheisen, M. Ripke, S. Yao, S. Giusti-Rodríguez, P. Hanscombe, K.B. Adan, R.A.H. Alfredsson, L. Ando, T. Andreassen, O.A. Berrettini, W.H. Boehm, I. Boni, C. Boraska Perica, V. Buehren, K. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Cone, R.D. Courtet, P. Crow, S. Crowley, J.J. Danner, U.N. Davis, O.S.P. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J.E. Dick, D.M. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo, E. Duncan, L.E. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M.M. Fischer, K. Föcker, M. Foretova, L. Forstner, A.J. Forzan, M. Franklin, C.S. Gallinger, S. Giegling, I. Giuranna, J. Gonidakis, F. Gorwood, P. Gratacos Mayora, M. Guillaume, S. Guo, Y. Hakonarson, H. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S.G. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Huckins, L.M. Hudson, J.I. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Julià, A. Kalsi, G. Kaminská, D. Karhunen, L. Karwautz, A. Kas, M.J.H. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Klump, K.L. Knudsen, G.P.S. La Via, M.C. Le Hellard, S. Levitan, R.D. Li, D. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P.J. Maj, M. Mannik, K. Marsal, S. Marshall, C.R. Mattingsdal, M. McDevitt, S. McGuffin, P. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, K. Monteleone, A.M. Monteleone, P. Nacmias, B. Navratilova, M. Ntalla, I. O'Toole, J.K. Ophoff, R.A. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Pinto, D. Rabionet, R. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Santonastaso, P. Scherag, A. Scherer, S.W. Schmidt, U. Schork, N.J. Schosser, A. Seitz, J. Slachtova, L. Slagboom, P.E. Slof-Op't Landt, M.C.T. Slopien, A. Sorbi, S. Świątkowska, B. Szatkiewicz, J.P. Tachmazidou, I. Tenconi, E. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A.A. van Furth, E.F. Wagner, G. Walton, E. Widen, E. Zeggini, E. Zerwas, S. Zipfel, S. Bergen, A.W. Boden, J.M. Brandt, H. Crawford, S. Halmi, K.A. Horwood, L.J. Johnson, C. Kaplan, A.S. Kaye, W.H. Mitchell, J. Olsen, C.M. Pearson, J.F. Pedersen, N.L. Strober, M. Werge, T. Whiteman, D.C. Woodside, D.B. Grove, J. Henders, A.K. Larsen, J.T. Parker, R. Petersen, L.V. Jordan, J. Kennedy, M.A. Birgegård, A. Lichtenstein, P. Norring, C. Landén, M. Mortensen, P.B. Polimanti, R. McClintick, J.N. Adkins, A.E. Aliev, F. Bacanu, S.-A. Batzler, A. Bertelsen, S. Biernacka, J.M. Bigdeli, T.B. Chen, L.-S. Clarke, T.-K. Degenhardt, F. Docherty, A.R. Edwards, A.C. Foo, J.C. Fox, L. Frank, J. Hack, L.M. Hartmann, A.M. Hartz, S.M. Heilmann-Heimbach, S. Hodgkinson, C. Hoffmann, P. Hottenga, J.-J. Konte, B. Lahti, J. Lahti-Pulkkinen, M. Lai, D. Ligthart, L. Loukola, A. Maher, B.S. Mbarek, H. McIntosh, A.M. McQueen, M.B. Meyers, J.L. Milaneschi, Y. Palviainen, T. Peterson, R.E. Ryu, E. Saccone, N.L. Salvatore, J.E. Sanchez-Roige, S. Schwandt, M. Sherva, R. Streit, F. Strohmaier, J. Thomas, N. Wang, J.-C. Webb, B.T. Wedow, R. Wetherill, L. Wills, A.G. Zhou, H. Boardman, J.D. Chen, D. Choi, D.-S. Copeland, W.E. Culverhouse, R.C. Dahmen, N. Degenhardt, L. Domingue, B.W. Frye, M.A. Gäebel, W. Hayward, C. Ising, M. Keyes, M. Kiefer, F. Koller, G. Kramer, J. Kuperman, S. Lucae, S. Lynskey, M.T. Maier, W. Mann, K. Männistö, S. Müller-Myhsok, B. Murray, A.D. Nurnberger, J.I. Preuss, U. Räikkönen, K. Reynolds, M.D. Ridinger, M. Scherbaum, N. Schuckit, M.A. Soyka, M. Treutlein, J. Witt, S.H. Wodarz, N. Zill, P. Adkins, D.E. Boomsma, D.I. Bierut, L.J. Brown, S.A. Bucholz, K.K. Costello, E.J. de Wit, H. Diazgranados, N. Eriksson, J.G. Farrer, L.A. Foroud, T.M. Gillespie, N.A. Goate, A.M. Goldman, D. Grucza, R.A. Hancock, D.B. Harris, K.M. Hesselbrock, V. Hewitt, J.K. Hopfer, C.J. Iacono, W.G. Johnson, E.O. Karpyak, V.M. Kendler, K.S. Kranzler, H.R. Krauter, K. Lind, P.A. McGue, M. MacKillop, J. Madden, P.A.F. Maes, H.H. Magnusson, P.K.E. Nelson, E.C. Nöthen, M.M. Palmer, A.A. Penninx, B.W.J.H. Porjesz, B. Rice, J.P. Rietschel, M. Riley, B.P. Rose, R.J. Shen, P.-H. Silberg, J. Stallings, M.C. Tarter, R.E. Vanyukov, M.M. Vrieze, S. Wall, T.L. Whitfield, J.B. Zhao, H. Neale, B.M. Wade, T.D. Heath, A.C. Montgomery, G.W. Martin, N.G. Sullivan, P.F. Kaprio, J. Breen, G. Gelernter, J. Edenberg, H.J. Bulik, C.M. Agrawal, A.

Subjects
mental disorders
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors. © 2020 Society for the Study of Addiction

Published
2021

45. Cytomegalovirus infection and IQ in patients with severe mental illness and healthy individuals

Author

Andreou, D. Jørgensen, K.N. Wortinger, L.A. Engen, K. Vaskinn, A. Ueland, T. Yolken, R.H. Andreassen, O.A. Agartz, I.

Subjects
virus diseases
Abstract

Cytomegalovirus (CMV) infection in immunocompetent adults is usually asymptomatic, but results in lifelong latency. Infection occurring congenitally or in immunodeficiency can lead to cognitive impairment. We aimed to investigate the associations between CMV exposure and intelligence quotient (IQ) in patients with schizophrenia spectrum disorders (SZS), bipolar spectrum disorders (BDS) and healthy controls (HC). CMV immunoglobulin G antibody concentrations were measured by immunoassay and expressed as dichotomous measures (seropositive/CMV+ vs. seronegative/CMV-). Based on a significant CMV-by-diagnosis-by-sex interaction on IQ, we investigated main and interaction effects of CMV and sex on IQ in each diagnostic category. Significant CMV-by-sex interactions were found in patient groups. In SZS, CMV+ female patients (n = 50) had significantly lower IQ than CMV- female patients (n = 33), whereas CMV+ (n = 48) and CMV- (n = 45) male patients did not differ in IQ. In BDS, CMV+ (n = 49) and CMV- (n = 37) female patients did not differ in IQ, whereas CMV+ male patients (n = 33) had significantly higher IQ than CMV- male patients (n = 32). Among HC, CMV+ (n = 138) and CMV- (n = 118) male participants as well as CMV+ (n = 125) and CMV- (n = 93) female participants did not differ in IQ. Our findings suggest that CMV exposure may affect IQ in patients with severe mental illness but not HC. © 2021 The Authors

Published
2021

46. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, M.A., Johnson, E.C., Chou, Y.L., Coleman, J.R.I., Thornton, L.M., Walters, R.K., Yilmaz, Z., Baker, J.H., Hübel, C., Gordon, S.D., Medland, S.E., Watson, H.J., Gaspar, H.A., Bryois, J., Hinney, A., Leppä, V.M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodríguez, P., Hanscombe, K.B., Adan, R.A.H., Alfredsson, L., Ando, T., Andreassen, O.A., Danner, U.N., Davis, O.S.P., de Zwaan, M., Dedoussis, G., Degortes, D., DeSocio, J.E., van Elburg, A.A., Munn-Chernoff, M.A., Johnson, E.C., Chou, Y.L., Coleman, J.R.I., Thornton, L.M., Walters, R.K., Yilmaz, Z., Baker, J.H., Hübel, C., Gordon, S.D., Medland, S.E., Watson, H.J., Gaspar, H.A., Bryois, J., Hinney, A., Leppä, V.M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodríguez, P., Hanscombe, K.B., Adan, R.A.H., Alfredsson, L., Ando, T., Andreassen, O.A., Danner, U.N., Davis, O.S.P., de Zwaan, M., Dedoussis, G., Degortes, D., DeSocio, J.E., and van Elburg, A.A.

Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotyp

Published
2021

47. Genetic control of variability in subcortical and intracranial volumes

Author

Córdova-Palomera, A., Meer, D. van der, Kaufmann, T., Bettella, F., Wang, Y., Alnæs, D., Doan, N.T., Agartz, I., Bertolino, A., Buitelaar, J.K., Coynel, D., Djurovic, S., Dørum, E.S., Espeseth, T., Fazio, L., Franke, B., Frei, O., Håberg, A., Hellard, S. Le, Jönsson, E.G., Kolskår, K.K., Lund, M.J., Moberget, T., Nordvik, J.E., Nyberg, L., Papassotiropoulos, A., Pergola, G., Quervain, D. de, Rampino, A., Richard, G., Rokicki, J., Sanders, A.M., Schwarz, E., Smeland, O.B., Steen, V.M., Starrfelt, J., Sønderby, I.E., Ulrichsen, K.M., Andreassen, O.A., Westlye, L.T., Córdova-Palomera, A., Meer, D. van der, Kaufmann, T., Bettella, F., Wang, Y., Alnæs, D., Doan, N.T., Agartz, I., Bertolino, A., Buitelaar, J.K., Coynel, D., Djurovic, S., Dørum, E.S., Espeseth, T., Fazio, L., Franke, B., Frei, O., Håberg, A., Hellard, S. Le, Jönsson, E.G., Kolskår, K.K., Lund, M.J., Moberget, T., Nordvik, J.E., Nyberg, L., Papassotiropoulos, A., Pergola, G., Quervain, D. de, Rampino, A., Richard, G., Rokicki, J., Sanders, A.M., Schwarz, E., Smeland, O.B., Steen, V.M., Starrfelt, J., Sønderby, I.E., Ulrichsen, K.M., Andreassen, O.A., and Westlye, L.T.

Abstract

Item does not contain fulltext, Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.

Published
2021

48. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author

Han, L.K.M., Dinga, R., Hahn, T., Ching, C.R., Eyler, L.T., Aftanas, L., Aghajani, M., Aleman, A., Baune, B.T., Berger, K., Brak, I., Filho, G.B., Carballedo, A., Connolly, C.G., Couvy-Duchesne, B., Cullen, K.R., Dannlowski, U., Davey, C.G., Dima, D., Duran, F.L.S., Enneking, V., Filimonova, E., Frenzel, S., Frodl, T., Fu, C.H.Y., Godlewska, B.R., Gotlib, I.H., Grabe, H.J., Groenewold, N.A., Grotegerd, D., Gruber, O., Hall, G.B., Harrison, B.J., Hatton, S.N., Hermesdorf, M., Hickie, I.B., Ho, T.C., Hosten, N., Jansen, Andreas, Kähler, C., Kircher, T., Klimes-Dougan, B., Krämer, B., Krug, A., Lagopoulos, J., Leenings, R., MacMaster, F.P., MacQueen, G., McIntosh, A., McLellan, Q., McMahon, K.L., Medland, S.E., Mueller, B.A., Mwangi, B., Osipov, E., Portella, M.J., Pozzi, E., Reneman, L., Repple, J., Rosa, P.G., Sacchet, M.D., Sämann, P.G., Schnell, K., Schrantee, A., Simulionyte, E., Soares, J.C., Sommer, J., Stein, D.J., Steinsträter, O., Strike, L.T., Thomopoulos, S.I., Tol, M.J.D. van, Veer, I.M., Vermeiren, R., Walter, H., Wee, N.J.A. van der, Werff, S.J.A. van der, Whalley, H., Winter, N.R., Wittfeld, K., Wright, M.J., Wu, M.J., Völzke, H., Yang, T.T., Zannias, V., Zubicaray, G.I. de, Zunta-Soares, G.B., Abé, C., Alda, M., Andreassen, O.A., Bøen, E., Bonnin, C.M., Canales-Rodriguez, E.J., Cannon, D., Caseras, X., Chaim-Avancini, T.M., Elvsåshagen, T., Favre, P., Foley, S.F., Fullerton, J.M., Ruhé, H.G., Schene, A.H., Marquand, A.F., Cole, J., Schmaal, L., Han, L.K.M., Dinga, R., Hahn, T., Ching, C.R., Eyler, L.T., Aftanas, L., Aghajani, M., Aleman, A., Baune, B.T., Berger, K., Brak, I., Filho, G.B., Carballedo, A., Connolly, C.G., Couvy-Duchesne, B., Cullen, K.R., Dannlowski, U., Davey, C.G., Dima, D., Duran, F.L.S., Enneking, V., Filimonova, E., Frenzel, S., Frodl, T., Fu, C.H.Y., Godlewska, B.R., Gotlib, I.H., Grabe, H.J., Groenewold, N.A., Grotegerd, D., Gruber, O., Hall, G.B., Harrison, B.J., Hatton, S.N., Hermesdorf, M., Hickie, I.B., Ho, T.C., Hosten, N., Jansen, Andreas, Kähler, C., Kircher, T., Klimes-Dougan, B., Krämer, B., Krug, A., Lagopoulos, J., Leenings, R., MacMaster, F.P., MacQueen, G., McIntosh, A., McLellan, Q., McMahon, K.L., Medland, S.E., Mueller, B.A., Mwangi, B., Osipov, E., Portella, M.J., Pozzi, E., Reneman, L., Repple, J., Rosa, P.G., Sacchet, M.D., Sämann, P.G., Schnell, K., Schrantee, A., Simulionyte, E., Soares, J.C., Sommer, J., Stein, D.J., Steinsträter, O., Strike, L.T., Thomopoulos, S.I., Tol, M.J.D. van, Veer, I.M., Vermeiren, R., Walter, H., Wee, N.J.A. van der, Werff, S.J.A. van der, Whalley, H., Winter, N.R., Wittfeld, K., Wright, M.J., Wu, M.J., Völzke, H., Yang, T.T., Zannias, V., Zubicaray, G.I. de, Zunta-Soares, G.B., Abé, C., Alda, M., Andreassen, O.A., Bøen, E., Bonnin, C.M., Canales-Rodriguez, E.J., Cannon, D., Caseras, X., Chaim-Avancini, T.M., Elvsåshagen, T., Favre, P., Foley, S.F., Fullerton, J.M., Ruhé, H.G., Schene, A.H., Marquand, A.F., Cole, J., and Schmaal, L.

Abstract

Item does not contain fulltext, Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

Published
2021

49. ENIGMA-Sleep: Challenges, opportunities, and the road map

Author

Tahmasian, M., Aleman, A., Andreassen, O.A., Arab, Z., Baillet, M., Benedetti, F. De, Bresser, T., Bright, J., Chee, M.W.L., Chylinski, D., Cheng, W., Deantoni, M., Dresler, M., Eickhoff, S.B., Eickhoff, C.R., Elvsåshagen, T., Feng, J., Foster-Dingley, J.C., Ganjgahi, H., Grabe, H.J., Groenewold, N.A., Ho, T.C., Hong, S., Houenou, J., Irungu, B., Jahanshad, N., Khazaie, H., Kim, H., Koshmanova, E., Kocevska, D., Kochunov, P., Lakbila-Kamal, O., Leerssen, J., Li, M., Luik, A.I., Muto, V., Narbutas, J., Nilsonne, G., O'Callaghan, V.S., Olsen, A., Osorio, R.S., Poletti, S., Poudel, G., Reesen, J.E., Reneman, L., Reyt, M., Riemann, D., Rosenzweig, I., Rostampour, M., Saberi, A., Schiel, J., Schmidt, C., Schrantee, A., Sciberras, E., Silk, T.J., Sim, K., Smevik, H., Soares, J.C., Spiegelhalder, K., Stein, D.J., Talwar, P., Tamm, S., Teresi, G.L., Valk, S.L., Someren, E. van, Vandewalle, G., Egroo, M. Van, Völzke, H., Walter, M., Wassing, R., Weber, F.D., Weihs, A., Westlye, L.T., Wright, M.J., Wu, M.J., Zak, N., Zarei, M., Tahmasian, M., Aleman, A., Andreassen, O.A., Arab, Z., Baillet, M., Benedetti, F. De, Bresser, T., Bright, J., Chee, M.W.L., Chylinski, D., Cheng, W., Deantoni, M., Dresler, M., Eickhoff, S.B., Eickhoff, C.R., Elvsåshagen, T., Feng, J., Foster-Dingley, J.C., Ganjgahi, H., Grabe, H.J., Groenewold, N.A., Ho, T.C., Hong, S., Houenou, J., Irungu, B., Jahanshad, N., Khazaie, H., Kim, H., Koshmanova, E., Kocevska, D., Kochunov, P., Lakbila-Kamal, O., Leerssen, J., Li, M., Luik, A.I., Muto, V., Narbutas, J., Nilsonne, G., O'Callaghan, V.S., Olsen, A., Osorio, R.S., Poletti, S., Poudel, G., Reesen, J.E., Reneman, L., Reyt, M., Riemann, D., Rosenzweig, I., Rostampour, M., Saberi, A., Schiel, J., Schmidt, C., Schrantee, A., Sciberras, E., Silk, T.J., Sim, K., Smevik, H., Soares, J.C., Spiegelhalder, K., Stein, D.J., Talwar, P., Tamm, S., Teresi, G.L., Valk, S.L., Someren, E. van, Vandewalle, G., Egroo, M. Van, Völzke, H., Walter, M., Wassing, R., Weber, F.D., Weihs, A., Westlye, L.T., Wright, M.J., Wu, M.J., Zak, N., and Zarei, M.

Abstract

Item does not contain fulltext, Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.

Published
2021

50. Differences in the Presentation and Progression of Parkinson's Disease by Sex

Author

Iwaki, H., Blauwendraat, C., Leonard, H.L., Makarious, M.B., Kim, J.J., Liu, G., Maple-Grødem, J., Corvol, J.C., Pihlstrøm, L., Nimwegen, M.L. van, Smolensky, L., Amondikar, N., Hutten, S.J., Frasier, M., Nguyen, K.H., Rick, J., Eberly, S., Faghri, F., Auinger, P., Scott, K.M., Wijeyekoon, R., Deerlin, V.M. Van, Hernandez, D.G., Gibbs, R.J., Day-Williams, A.G., Brice, A., Alves, G., Noyce, A.J., Tysnes, O.B., Evans, J.R., Breen, D.P., Estrada, K., Wegel, C.E., Danjou, F., Simon, D.K., Andreassen, O.A., Ravina, B., Toft, M., Heutink, P., Bloem, B.R., Weintraub, D., Barker, R.A., Williams-Gray, C.H., Warrenburg, B.P.C. van de, Hilten, J.J. van, Scherzer, C.R., Singleton, A.B., Nalls, M.A., Iwaki, H., Blauwendraat, C., Leonard, H.L., Makarious, M.B., Kim, J.J., Liu, G., Maple-Grødem, J., Corvol, J.C., Pihlstrøm, L., Nimwegen, M.L. van, Smolensky, L., Amondikar, N., Hutten, S.J., Frasier, M., Nguyen, K.H., Rick, J., Eberly, S., Faghri, F., Auinger, P., Scott, K.M., Wijeyekoon, R., Deerlin, V.M. Van, Hernandez, D.G., Gibbs, R.J., Day-Williams, A.G., Brice, A., Alves, G., Noyce, A.J., Tysnes, O.B., Evans, J.R., Breen, D.P., Estrada, K., Wegel, C.E., Danjou, F., Simon, D.K., Andreassen, O.A., Ravina, B., Toft, M., Heutink, P., Bloem, B.R., Weintraub, D., Barker, R.A., Williams-Gray, C.H., Warrenburg, B.P.C. van de, Hilten, J.J. van, Scherzer, C.R., Singleton, A.B., and Nalls, M.A.

Abstract

Item does not contain fulltext, BACKGROUND: Previous studies reported various symptoms of Parkinson's disease (PD) associated with sex. Some were conflicting or confirmed in only one study. OBJECTIVES: We examined sex associations to PD phenotypes cross-sectionally and longitudinally in large-scale data. METHODS: We tested 40 clinical phenotypes, using longitudinal, clinic-based patient cohorts, consisting of 5946 patients, with a median follow-up of 3.1 years. For continuous outcomes, we used linear regressions at baseline to test sex-associated differences in presentation, and linear mixed-effects models to test sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox regression models for survival analyses. We adjusted for age, disease duration, and medication use. In the secondary analyses, data from 17 719 PD patients and 7588 non-PD participants from an online-only, self-assessment PD cohort were cross-sectionally evaluated to determine whether the sex-associated differences identified in the primary analyses were consistent and unique to PD. RESULTS: Female PD patients had a higher risk of developing dyskinesia early during the follow-up period, with a slower progression in activities of daily living difficulties, and a lower risk of developing cognitive impairments compared with male patients. The findings in the longitudinal, clinic-based cohorts were mostly consistent with the results of the online-only cohort. CONCLUSIONS: We observed sex-associated contributions to PD heterogeneity. These results highlight the necessity of future research to determine the underlying mechanisms and importance of personalized clinical management. © 2020 International Parkinson and Movement Disorder Society.

Published
2021

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