Freimer, Nelson B.
https://orcid.org/0000-0003-3586-6587
Mayo Clinic
University of California, Los Angeles
Citations 2
Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder
Veen, Tracey van der , Tesfaye, Markos , Yang, Jessica , Boltz, Toni , David, Friederike S. , Crinion, Shane , Koromina, Maria , Bigdeli, Tim B., Coombes, Brandon J., Panagiotaropoulou, Georgia, Parker, Nadine, Sung, Heejong , Bass, Nicholas, Coleman, Jonathan R. I., Guzman-Parra, José , Kálmán, János , McGrouther, Caroline C., Rangan, Aaditya V. , Scott, Katie , Vreeker, Annabel , Bauer, Michael , Brunkhorst-Kanaan, Nathalie, Byerley, William , Cervantes, Pablo , Chatzinakos, Chris , Claus, Isabelle , Cruceanu, Cristiana , Cuellar-Barboza, Alfredo, Dafnas, Konstantinos , Degenhardt, Franziska, Fanous, Ayman H. , Ferrier, I. Nicol , Forty, Liz , Frank, Josef , Freimer, Nelson B. , Hamshere, Marian L., Harder, Arvid , Hautzinger, Martin , Hellgren, Dennis, Hoffmann, Per, Jönsson, Lina , Kittel‐Schneider, Sarah , Knowles, James A. , Lavebratt, Catharina , Lawrence, Jacob , Leber, Markus , Lucae, Susanne , Lundberg, Martin , Maier, Wolfgang , Maihofer, Adam X. , Maratou, Eirini , McKay, James , Medeiros, Helena , Meyer‐Lindenberg, Andreas , Moutsatsou, Paraskevi , Mühleisen, Thomas W. , O’Connell, Kevin S. , Papiol, Sergi , Perry, Amy , Pisanu, Claudia , Potash, James B. , Rapaport, Mark Hyman , Regeer, Eline J. , Rice, John P. , Schulte, Eva C. , Senner, Fanny , Shilling, Paul D. , Sirignano, Lea , Slaney, Claire , Smeland, Olav B. , Sobell, Janet L. , Stein, Dan J. , Vawter, Marquis P. , Vedder, Helmut , Witt, Stephanie H. , Zandi, Peter P. , Investigators, Genomic Psychiatry Cohort (GPC), Psychiatry, HUNT All-In, Bengesser, Susanne , Berrettini, Wade H. , Blackwood, Douglas, Boehnke, Michael , Catts, Stanley V. , Craddock, Nicholas , Dikeos, Dimitris , Ferentinos, Panagiotis , Frye, Mark A. , Gawlik, Micha , Kahn, René S., Landén, Mikael , Lenger, Melanie , Loughland, Carmel , Melle, Ingrid , Myers, R , Müller‐Myhsok, Bertram , Neale, Benjamin M. , Øedegaard, Ketil J. , Paciga, Sara A. , Pato, Carlos N. , Pawlak, Joanna , Perlis, Roy H. , Reif, Andreas , Schalling, Martin , Scott, Laura J. , Scott, Rodney J., Stahl, Eli A. , Stordal, Eystein , Sullivan, Patrick F., Vaaler, Arne E. , Waldman, Irwin D. , Ophoff, Roel A. , Mullins, Niamh , Forstner, Andreas J. , van der Veen, Tracey , Yang, Jessica Mei Kay , Alda, Martin , Ophoff, Roel A , O'Connell, Kevin S , Mullins, Niamh , Forstner, Andreas J , Grigoroiu-Serbanescu, Maria , Edenberg, Howard J , McMahon, Francis , Andreassen, Ole A , Di Florio, Arianna , McQuillin, Andrew , Witt, Stephanie H , Meyer-Lindenberg, Andreas , Stein, Dan J , Papiol, Sergi , Cruceanu, Cristiana , Schulte, Eva , Kittel-Schneider, Sarah , Lavebratt, Catharina , Pisanu, Claudia , Reif, Andreas , Perlis, Roy H , Andlauer, Till F. M. , Bigdeli, Tim B. , Coombes, Brandon J. , Greenwood, Tiffany A. , Panagiotaropoulou, Georgia , Parker, Nadine , Bass, Nicholas, Coleman, Jonathan Ri , Mitchell, Brittany L. , Shadrin, Alexey A. , Smith, Daniel J. , Adorjan, Kristina , Albani, Diego , Alemany, Silvia , Alliey‐Rodriguez, Ney , Antoniou, Anastasia , Beins, Eva Carolina , Boks, Marco P. , Bosch, Rosa , Brumpton, Ben , Budde, Monika , Cabana‐Domínguez, Judit , Cairns, Murray J. , Carpiniello, Bernardo , Casas, Miguel , Clarke, Toni‐Kim , Cuéllar‐Barboza, Alfredo B. , Czerski, Piotr M. , Dale, Anders M. , Dalkner, Nina , DePaulo, J Raymond , Djurovic, Srdjan , Escott‐Price, Valentina , Fellendorf, Frederike T. , Frei, Oleksandr , Garnham, Julie , Gizer, Ian R. , Gordon, Scott D. , Gordon‐Smith, Katherine , Hahn, Tim , Hamshere, Marian L. , Heilbronner, Urs , Herms, Stefan , Hickie, Ian Bernard , Hoffmann, Per , Holmans, Peter , Jamain, Stéphane , Kennedy, James L. , Koch, Elise , Kogevinas, Manolis , Kranz, Thorsten M. , Kushner, Steven A. , Lind, Penelope A. , Lundberg, Martin, MacIntyre, Donald J. , Malaspina, Dolores , Manchia, Mirko , Martinsson, Lina , McInnis, Melvin G. , Millischer, Vincent , Morris, Derek W. , Olsen, Catherine M. , Pardiñas, Antonio F. , Pfennig, Andrea , Quested, Digby J. , Rivera, Margarita , Sindermann, Lisa , Siskind, Dan , Artigas, María Soler , Stein, Frederike , Świątkowska, Beata , Thorp, Jackson G. , Toma, Claudio , Tondo, Leonardo , Tooney, Paul A. , Walters, James , Young, Allan H. , Zillich, Lea , Adolfsson, Rolf , Alfredsson, Lars , Backlund, Lena , Baune, Bernhard , Bellivier, Frank , Biernacka, Joanna M. , Blackwood, Douglas , Breen, Gerome , Carr, Vaughan J , Cichon, Sven , Corvin, Aiden , Dannlowski, Udo , Esko, Tõnu , Étain, Bruno , Fullerton, Janice M. , Gershon, Elliot S. , Goes, Fernando , Green, Melissa J. , Hauser, Joanna , Henskens, Frans A , Hjerling‐Leffler, Jens , Jones, Ian Richard , Jones, Lisa Anne , Kahn, René S. , Kelsoe, John R , Kircher, Tilo , Kirov, George , Kobayashi, Nene, Leboyer, Marion , Li, Qingqin S. , Lissowska, Jolanta , Loughland, Carmel M. , Luykx, Jurjen J. , Martin, Nicholas G. , Mathews, Carol A. , Mayoral, Fermín , McElroy, Susan L. , McIntosh, Andrew M. , Medland, Sarah E. , Mitchell, Philip B , Morken, Gunnar , Möser, Chiara, Nievergelt, Caroline M , Nurnberger, John I , Nöthen, Markus M. , O‘Donovan, Michael , Olsson, Tomas , Owen, Michael J. , Pantelis, Christos , Pato, Michele T. , Patrinos, George P. , Ramos‐Quiroga, Josep Antoni , Reininghaus, Eva , Ribasés, Marta , Rietschel, Marcella , Ripke, Stephan , Rouleau, Guy Armand , Schall, Ulrich , Schofield, Peter R. , Schulze, Thomas , Scott, Rodney J. , Serretti, Alessandro , Smoller, Jordan W. , Squassina, Alessio , Streit, Fabian , Turecki, Gustavo , Vieta, Eduard , Vincent, John B. , Weickert, Cynthia Shannon , Weickert, Thomas Wesley , Whiteman, David C. , Alda, Martin , Grigoroiu‐Serbânescu, Maria , McMahon, Francis J. , Andreassen, Ole A. , McQuillin, Andrew
No container title available | June 25, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.
Country-level gender inequality is associated with structural differences in the brains of women and men
Alliende, Luz María , Medel, Vicente , Bethlehem, Richard A. I. , Ringlein, Grace , Arango, Celso , Asmal, Laila , Bellgrove, Mark A. , Bernardo, Miquel , Billeke, Pablo , Bosch‐Bayard, Jorge , Busatto, Geraldo F. , Castro, Mariana N. , Chaim-Avancini, Tiffany , Compte, Albert , Costanzi, Monise , Dazzan, Paola , Fuente‐Sandoval, Camilo de la , Díaz‐Zuluaga, Ana M. , Duran, Fábio , Fittipaldi, Sol , Fornito, Alex , Freimer, Nelson B. , Gadelha, Ary , Gama, Clarissa Severino , Ramesh, Ranjini Garani , García‐Rizo, Clemente , Campo, Cecilia González , González‐Valderrama, Alfonso , Holla, Bharath , Ibáñez, Agustín , Ivanovic, Daniza , Jackowski, Andrea Parolin , Löchner, Christine , López‐Jaramillo, Carlos , Massuda, Raffael , McGuire, Philip , Murray, Robin , Özerdem, Ayşegül , Pan, Pedro Mário , Parellada, Mara , Phahladira, Lebogan, Ramírez-Mahaluf, Juan Pablo , Reyes-Madrigal, Francisco , Roos, Annerine , Scheffler, Freda , Stein, Dan J. , Tepper, Ángeles , Ueno, Tsukasa, Undurraga, Juan , Valli, Isabel , Villarreal, Mirta F. , Yalın, Nefize , Zamorano, Francisco , Zanetti, Marcus V. , cVEDA, Pine, Daniel S. , Evans‐Lacko, Sara , Crossley, Nicolás , Murthy, Pratima , Chakrabarti, Amit , Basu, Debasish , Subodh, B. N., Singh, Lenin, Singh, Roshan Lourembam, Kalyanram, Kartik , Kartik, Kamakshi, Kurpad, Sunita Simon , Bharath, Rose Dawn , Orfanos, Dimitri Papadopoulos , Sharma, Eesha , Alliende, Luz María , Medel, Vicente , Bethlehem, Richard A I , Benegal, Vivek , Bernardo, Miquel , Billeke, Pablo , Busatto, Geraldo F , Castro, Mariana N , Czepielewski, Leticia , de la Fuente-Sandoval, Camilo , Duran, Fabio L S , Fittipaldi, Sol , Fornito, Alex , Garani, Ranjini , Guinjoan, Salvador , Ibañez, Agustín , Ivanovic, Daniza , Lochner, Christine , Massuda, Raffael , Miyata, Jun , Mizrahi, Romina , Murray, Robin , Ramirez-Mahaluf, Juan P , Reis Marques, Tiago , Reyes-Madrigal, Francisco , Roos, Annerine , Salum, Giovanni , Stein, Dan J , Tepper, Angeles , Undurraga, Juan , Undurraga, Eduardo A , Valdes-Sosa, Pedro , Valli, Isabel , Zamorano, Francisco , Crossley, Nicolas A , López-Jaramillo, Carlos , Ozerdem, Aysegul , Yalin, Nefize , Zugman, André , Seidlitz, Jakob , Arnatkevičiūtė, Aurina , Bressan, Rodrigo A. , Forti, Marta Di , Díaz‐Caneja, Covadonga M. , Plessis, Stefan S. du , León-Ortíz, Pablo , Luckhoff, Hilmar Klaus , Phahladira, Lebogang , Reckziegel, Ramiro de Freitas Xavier , Rosa-Neto, Pedro , Serpa, Maurício Henriques , Winton‐Brown, Toby , cVEDA, Winkler, Anderson M. , Kartik, Kamakshi , Kumaran, Kalyanaraman , Krishnaveni, Ghattu Vedamurthy , Kuriyan, Rebecca , Barker, Gareth J. , Desrivières, Sylvane , Purushottam, Meera , Hickman, Matthew , Heron, Jon , Toledano, Mireille B. , Vaidya, Nilakshi
Proceedings of the National Academy of Sciences | May 8, 2023 | Volume: 120 | Issue: 20 | Pages: No page available
Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality.