665 results on '"Turetsky, Bruce I."'
Search Results
2. Anticholinergic Medication Burden–Associated Cognitive Impairment in Schizophrenia
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Joshi, Yash B, Thomas, Michael L, Braff, David L, Green, Michael F, Gur, Ruben C, Gur, Raquel E, Nuechterlein, Keith H, Stone, William S, Greenwood, Tiffany A, Lazzeroni, Laura C, MacDonald, Laura R, Molina, Juan L, Nungaray, John A, Radant, Allen D, Silverman, Jeremy M, Sprock, Joyce, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Swerdlow, Neal R, and Light, Gregory A
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Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Clinical Research ,Behavioral and Social Science ,Schizophrenia ,Serious Mental Illness ,Neurosciences ,Brain Disorders ,Mental Health ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Mental health ,Adolescent ,Adult ,Aged ,Cholinergic Antagonists ,Cognition ,Cognitive Dysfunction ,Cohort Studies ,Cross-Sectional Studies ,Humans ,Middle Aged ,Neuropsychological Tests ,Young Adult ,Anticholinergics ,Cognition/Learning/Memory ,Psychopharmacology ,Schizophrenia Spectrum and Other Psychotic Disorders ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Clinical and health psychology - Abstract
ObjectiveMany psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.MethodsCross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).ResultsACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.ConclusionsAnticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.
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- 2021
3. Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia
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Greenwood, Tiffany A, Swerdlow, Neal R, Sprock, Joyce, Calkins, Monica E, Freedman, Robert, Green, Michael F, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Light, Gregory A, Nuechterlein, Keith H, Radant, Allen D, Silverman, Jeremy M, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Braff, David L, and Duncan, Erica
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Neurosciences ,Clinical Research ,Schizophrenia ,Brain Disorders ,Genetics ,Mental Health ,Acoustic Stimulation ,Acoustics ,Humans ,Prepulse Inhibition ,Reflex ,Startle ,Latency ,Heritability ,Acoustic startle ,Endophenotype ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
BackgroundLatency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertaken to replicate and extend this solitary finding in a larger cohort.MethodsSchizophrenia probands, their relatives, and control subjects from the Consortium on the Genetics of Schizophrenia (COGS-1) were tested in a paradigm to ascertain magnitude, latency, and prepulse inhibition of startle. Trial types in the paradigm were: pulse-alone, and trials with 30, 60, or 120 ms between the prepulse and pulse. Comparisons of subject groups were conducted with ANCOVAs to assess startle latency and magnitude. Heritability of startle magnitude and latency was analyzed with a variance component method implemented in SOLAR v.4.3.1.Results980 subjects had analyzable startle results: 199 schizophrenia probands, 456 of their relatives, and 325 controls. A mixed-design ANCOVA on startle latency in the four trial types was significant for subject group (F(2,973) = 4.45, p = 0.012) such that probands were slowest, relatives were intermediate and controls were fastest. Magnitude to pulse-alone trials differed significantly between groups by ANCOVA (F(2,974) = 3.92, p = 0.020) such that controls were lowest, probands highest, and relatives intermediate. Heritability was significant (p
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- 2020
4. The effects of age and sex on cognitive impairment in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS) study
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Lee, Junghee, Green, Michael F, Nuechterlein, Keith H, Swerdlow, Neal R, Greenwood, Tiffany A, Hellemann, Gerhard S, Lazzeroni, Laura C, Light, Gregory A, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Gur, Ruben C, Gur, Raquel E, and Braff, David L
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Biomedical and Clinical Sciences ,Applied and Developmental Psychology ,Biological Psychology ,Psychology ,Pharmacology and Pharmaceutical Sciences ,Schizophrenia ,Behavioral and Social Science ,Mental Health ,Neurosciences ,Basic Behavioral and Social Science ,Brain Disorders ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Adult ,Age Factors ,Aged ,Case-Control Studies ,Cognitive Dysfunction ,Female ,Humans ,Linear Models ,Male ,Memory ,Short-Term ,Middle Aged ,Neuropsychological Tests ,Schizophrenic Psychology ,Sex Factors ,Young Adult ,General Science & Technology - Abstract
Recently emerging evidence indicates accelerated age-related changes in the structure and function of the brain in schizophrenia, raising a question about its potential consequences on cognitive function. Using a large sample of schizophrenia patients and controls and a battery of tasks across multiple cognitive domains, we examined whether patients show accelerated age-related decline in cognition and whether an age-related effect differ between females and males. We utilized data of 1,415 schizophrenia patients and 1,062 healthy community collected by the second phase of the Consortium on the Genetics of Schizophrenia (COGS-2). A battery of cognitive tasks included the Letter-Number Span Task, two forms of the Continuous Performance Test, the California Verbal Learning Test, Second Edition, the Penn Emotion Identification Test and the Penn Facial Memory Test. The effect of age and gender on cognitive performance was examined with a general linear model. We observed age-related changes on most cognitive measures, which was similar between males and females. Compared to controls, patients showed greater deterioration in performance on attention/vigilance and greater slowness of processing social information with increasing age. However, controls showed greater age-related changes in working memory and verbal memory compared to patients. Age-related changes (η2p of 0.001 to .008) were much smaller than between-group differences (η2p of 0.005 to .037). This study found that patients showed continued decline of cognition on some domains but stable impairment or even less decline on other domains with increasing age. These findings indicate that age-related changes in cognition in schizophrenia are subtle and not uniform across multiple cognitive domains.
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- 2020
5. Genome-wide Association of Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia (COGS) Study
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Greenwood, Tiffany A, Lazzeroni, Laura C, Maihofer, Adam X, Swerdlow, Neal R, Calkins, Monica E, Freedman, Robert, Green, Michael F, Light, Gregory A, Nievergelt, Caroline M, Nuechterlein, Keith H, Radant, Allen D, Siever, Larry J, Silverman, Jeremy M, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Gur, Ruben C, Gur, Raquel E, and Braff, David L
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Schizophrenia ,Neurosciences ,Human Genome ,Genetics ,Mental Health ,Clinical Research ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Good Health and Well Being ,Adult ,Cognitive Dysfunction ,Endophenotypes ,Female ,Genome-Wide Association Study ,Humans ,Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ,Male ,Middle Aged ,Neuregulins ,Potassium Channels ,Other Medical and Health Sciences ,Psychology ,Cognitive Sciences - Abstract
ImportanceThe Consortium on the Genetics of Schizophrenia (COGS) uses quantitative neurophysiological and neurocognitive endophenotypes with demonstrated deficits in schizophrenia as a platform from which to explore the underlying neural circuitry and genetic architecture. Many of these endophenotypes are associated with poor functional outcome in schizophrenia. Some are also endorsed as potential treatment targets by the US Food and Drug Administration.ObjectiveTo build on prior assessments of heritability, association, and linkage in the COGS phase 1 (COGS-1) families by reporting a genome-wide association study (GWAS) of 11 schizophrenia-related endophenotypes in the independent phase 2 (COGS-2) cohort of patients with schizophrenia and healthy comparison participants (HCPs).Design, setting, and participantsA total of 1789 patients with schizophrenia and HCPs of self-reported European or Latino ancestry were recruited through a collaborative effort across the COGS sites and genotyped using the PsychChip. Standard quality control filters were applied, and more than 6.2 million variants with a genotyping call rate of greater than 0.99 were available after imputation. Association was performed for data sets stratified by diagnosis and ancestry using linear regression and adjusting for age, sex, and 5 principal components, with results combined through weighted meta-analysis. Data for COGS-1 were collected from January 6, 2003, to August 6, 2008; data for COGS-2, from June 30, 2010, to February 14, 2014. Data were analyzed from October 28, 2016, to May 4, 2018.Main outcomes and measuresA genome-wide association study was performed to evaluate association for 11 neurophysiological and neurocognitive endophenotypes targeting key domains of schizophrenia related to inhibition, attention, vigilance, learning, working memory, executive function, episodic memory, and social cognition.ResultsThe final sample of 1533 participants included 861 male participants (56.2%), and the mean (SD) age was 41.8 (13.6) years. In total, 7 genome-wide significant regions (P
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- 2019
6. Nonlinear dynamics underlying sensory processing dysfunction in schizophrenia
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Lainscsek, Claudia, Sampson, Aaron L, Kim, Robert, Thomas, Michael L, Man, Karen, Lainscsek, Xenia, Swerdlow, Neal R, Braff, David L, Sejnowski, Terrence J, Light, Gregory A, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Radant, Allen D, Seidman, Larry J, Sharp, Richard F, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, and Turetsky, Bruce I
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Serious Mental Illness ,Mental Health ,Schizophrenia ,Brain Disorders ,Neurosciences ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Good Health and Well Being ,Acoustic Stimulation ,Adult ,Attention ,Brain ,Cognition ,Electroencephalography ,Evoked Potentials ,Auditory ,Female ,Humans ,Male ,Middle Aged ,Nonlinear Dynamics ,Sensation ,nonlinear dynamics ,delay differential analysis ,mismatch negativity ,schizophrenia ,EEG ,COGS Investigators - Abstract
Natural systems, including the brain, often seem chaotic, since they are typically driven by complex nonlinear dynamical processes. Disruption in the fluid coordination of multiple brain regions contributes to impairments in information processing and the constellation of symptoms observed in neuropsychiatric disorders. Schizophrenia (SZ), one of the most debilitating mental illnesses, is thought to arise, in part, from such a network dysfunction, leading to impaired auditory information processing as well as cognitive and psychosocial deficits. Current approaches to neurophysiologic biomarker analyses predominantly rely on linear methods and may, therefore, fail to capture the wealth of information contained in whole EEG signals, including nonlinear dynamics. In this study, delay differential analysis (DDA), a nonlinear method based on embedding theory from theoretical physics, was applied to EEG recordings from 877 SZ patients and 753 nonpsychiatric comparison subjects (NCSs) who underwent mismatch negativity (MMN) testing via their participation in the Consortium on the Genetics of Schizophrenia (COGS-2) study. DDA revealed significant nonlinear dynamical architecture related to auditory information processing in both groups. Importantly, significant DDA changes preceded those observed with traditional linear methods. Marked abnormalities in both linear and nonlinear features were detected in SZ patients. These results illustrate the benefits of nonlinear analysis of brain signals and underscore the need for future studies to investigate the relationship between DDA features and pathophysiology of information processing.
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- 2019
7. Semantic processing features and schizotypal traits: A test-retest study
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Yu, Xinyang, Liao, Keren, Turetsky, Bruce I., and Wang, Kui
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- 2022
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8. Mapping genomic loci implicates genes and synaptic biology in schizophrenia
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Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey S., Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C., Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L., Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G., Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Alptekin, Köksal, Als, Thomas D., Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A., Bass, Nicholas J., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Benyamin, Beben, Bergen, Sarah E., Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J., Bruggeman, Richard, Buckley, Peter F., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J., Calkins, Monica E., Carr, Vaughan J., Castle, David, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C. K., Chaumette, Boris, Cheng, Wei, Cheung, Eric F. C., Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L., de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanás, Lourdes, Faraone, Stephen V., Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B., Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Giannitelli, Marianna, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., González Peñas, Javier, González-Pinto, Ana, Gopal, Srihari, Gratten, Jacob, Green, Michael F., Greenwood, Tiffany A., Guillin, Olivier, Gülöksüz, Sinan, Gur, Raquel E., Gur, Ruben C., Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Haroutunian, Vahram, Hartmann, Annette M., Harvey, Carol, Hayward, Caroline, Henskens, Frans A., Herms, Stefan, Hoffmann, Per, Howrigan, Daniel P., Ikeda, Masashi, Iyegbe, Conrad, Joa, Inge, Julià, Antonio, Kähler, Anna K., Kam-Thong, Tony, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Kebir, Oussama, Keller, Matthew C., Kelly, Brian J., Khrunin, Andrey, Kim, Sung-Wan, Klovins, Janis, Kondratiev, Nikolay, Konte, Bettina, Kraft, Julia, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C., Lee, Phil H., Legge, Sophie E., Lehrer, Douglas S., Lencer, Rebecca, Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Light, Gregory A., Limborska, Svetlana, Liu, Chih-Min, Lönnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Luykx, Jurjen J., Lynham, Amy, Macek, Jr, Milan, Mackinnon, Andrew, Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Malaspina, Dolores, Mallet, Jacques, Marder, Stephen R., Marsal, Sara, Martin, Alicia R., Martorell, Lourdes, Mattheisen, Manuel, McCarley, Robert W., McDonald, Colm, McGrath, John J., Medeiros, Helena, Meier, Sandra, Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mitjans, Marina, Molden, Espen, Molina, Esther, Molto, María Dolores, Mondelli, Valeria, Moreno, Carmen, Morley, Christopher P., Muntané, Gerard, Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Nikitina-Zake, Liene, Noto, Cristiano, Nuechterlein, Keith H., O’Brien, Niamh Louise, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Ota, Vanessa Kiyomi, Pantelis, Christos, Papadimitriou, George N., Parellada, Mara, Paunio, Tiina, Pellegrino, Renata, Periyasamy, Sathish, Perkins, Diana O., Pfuhlmann, Bruno, Pietiläinen, Olli, Pimm, Jonathan, Porteous, David, Powell, John, Quattrone, Diego, Quested, Digby, Radant, Allen D., Rampino, Antonio, Rapaport, Mark H., Rautanen, Anna, Reichenberg, Abraham, Roe, Cheryl, Roffman, Joshua L., Roth, Julian, Rothermundt, Matthias, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veikko, Sanjuan, Julio, Santoro, Marcos Leite, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Seidman, Larry J., Sharp, Sally Isabel, Shi, Jianxin, Siever, Larry J., Sigurdsson, Engilbert, Sim, Kang, Skarabis, Nora, Slominsky, Petr, So, Hon-Cheong, Sobell, Janet L., Söderman, Erik, Stain, Helen J., Steen, Nils Eiel, Steixner-Kumar, Agnes A., Stögmann, Elisabeth, Stone, William S., Straub, Richard E., Streit, Fabian, Strengman, Eric, Stroup, T. Scott, Subramaniam, Mythily, Sugar, Catherine A., Suvisaari, Jaana, Svrakic, Dragan M., Swerdlow, Neal R., Szatkiewicz, Jin P., Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Toncheva, Draga, Tooney, Paul A., Torretta, Silvia, Tosato, Sarah, Tura, Gian Battista, Turetsky, Bruce I., Üçok, Alp, Vaaler, Arne, van Amelsvoort, Therese, van Winkel, Ruud, Veijola, Juha, Waddington, John, Walter, Henrik, Waterreus, Anna, Webb, Bradley T., Weiser, Mark, Williams, Nigel M., Witt, Stephanie H., Wormley, Brandon K., Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C., Zhou, Wei, Zhu, Feng, Zimprich, Fritz, Atbaşoğlu, Eşref Cem, Ayub, Muhammad, Benner, Christian, Bertolino, Alessandro, Black, Donald W., Bray, Nicholas J., Breen, Gerome, Buccola, Nancy G., Byerley, William F., Chen, Wei J., Cloninger, C. Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Freedman, Robert, Galletly, Cherrie, Gandal, Michael J., Gennarelli, Massimo, Hougaard, David M., Hwu, Hai-Gwo, Jablensky, Assen V., McCarroll, Steven A., Moran, Jennifer L., Mors, Ole, Mortensen, Preben B., Müller-Myhsok, Bertram, Neil, Amanda L., Nordentoft, Merete, Pato, Michele T., Petryshen, Tracey L., Pirinen, Matti, Pulver, Ann E., Schulze, Thomas G., Silverman, Jeremy M., Smoller, Jordan W., Stahl, Eli A., Tsuang, Debby W., Vilella, Elisabet, Wang, Shi-Heng, Xu, Shuhua, Adolfsson, Rolf, Arango, Celso, Baune, Bernhard T., Belangero, Sintia Iole, Børglum, Anders D., Braff, David, Bramon, Elvira, Buxbaum, Joseph D., Campion, Dominique, Cervilla, Jorge A., Cichon, Sven, Collier, David A., Corvin, Aiden, Curtis, David, Forti, Marta Di, Domenici, Enrico, Ehrenreich, Hannelore, Escott-Price, Valentina, Esko, Tõnu, Fanous, Ayman H., Gareeva, Anna, Gawlik, Micha, Gejman, Pablo V., Gill, Michael, Glatt, Stephen J., Golimbet, Vera, Hong, Kyung Sue, Hultman, Christina M., Hyman, Steven E., Iwata, Nakao, Jönsson, Erik G., Kahn, René S., Kennedy, James L., Khusnutdinova, Elza, Kirov, George, Knowles, James A., Krebs, Marie-Odile, Laurent-Levinson, Claudine, Lee, Jimmy, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., Malhotra, Dheeraj, McIntosh, Andrew, McQuillin, Andrew, Menezes, Paulo R., Morgan, Vera A., Morris, Derek W., Mowry, Bryan J., Murray, Robin M., Nimgaonkar, Vishwajit, Nöthen, Markus M., Ophoff, Roel A., Paciga, Sara A., Palotie, Aarno, Pato, Carlos N., Qin, Shengying, Rietschel, Marcella, Riley, Brien P., Rivera, Margarita, Rujescu, Dan, Saka, Meram C., Sanders, Alan R., Schwab, Sibylle G., Serretti, Alessandro, Sham, Pak C., Shi, Yongyong, St Clair, David, Stefánsson, Hreinn, Stefansson, Kari, Tsuang, Ming T., van Os, Jim, Vawter, Marquis P., Weinberger, Daniel R., Werge, Thomas, Wildenauer, Dieter B., Yu, Xin, Yue, Weihua, Holmans, Peter A., Pocklington, Andrew J., Roussos, Panos, Vassos, Evangelos, Verhage, Matthijs, Visscher, Peter M., Yang, Jian, Posthuma, Danielle, Andreassen, Ole A., Kendler, Kenneth S., Owen, Michael J., Wray, Naomi R., Daly, Mark J., Huang, Hailiang, Neale, Benjamin M., Sullivan, Patrick F., Ripke, Stephan, Walters, James T. R., and O’Donovan, Michael C.
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- 2022
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9. Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia
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Wolf, Daniel H., Zheng, David, Kohler, Christian, Turetsky, Bruce I., Ruparel, Kosha, Satterthwaite, Theodore D., Elliott, Mark A., March, Mary E., Cross, Alan J., Smith, Mark A., Zukin, Stephen R., Gur, Ruben C., and Gur, Raquel E.
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- 2022
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10. Deficient prepulse inhibition in schizophrenia in a multi-site cohort: Internal replication and extension.
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Swerdlow, Neal R, Light, Gregory A, Thomas, Michael L, Sprock, Joyce, Calkins, Monica E, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Braff, David L
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Humans ,Gait Disorders ,Neurologic ,Antipsychotic Agents ,Acoustic Stimulation ,Analysis of Variance ,Cohort Studies ,Schizophrenia ,Psychiatric Status Rating Scales ,Neural Inhibition ,Adolescent ,Adult ,Middle Aged ,Female ,Male ,Young Adult ,Endophenotypes ,Prepulse Inhibition ,Endophenotype ,Prepulse inhibition ,Replication ,Startle ,Clinical Research ,Mental Health ,Brain Disorders ,Aetiology ,2.1 Biological and endogenous factors ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
BackgroundThe Consortium on the Genetics of Schizophrenia (COGS) collected case-control endophenotype and genetic information from 2457 patients and healthy subjects (HS) across 5 test sites over 3.5 years. Analysis of the first "wave" (W1) of 1400 subjects identified prepulse inhibition (PPI) deficits in patients vs. HS. Data from the second COGS "wave" (W2), and the combined W(1+2), were used to assess: 1) the replicability of PPI deficits in this design; 2) the impact of response criteria on PPI deficits; and 3) PPI in a large cohort of antipsychotic-free patients.MethodsPPI in W2 HS (n=315) and schizophrenia patients (n=326) was compared to findings from W1; planned analyses assessed the impact of diagnosis, "wave" (1 vs. 2), and startle magnitude criteria. Combining waves allowed us to assess PPI in 120 antipsychotic-free patients, including many in the early course of illness.ResultsANOVA of all W(1+2) subjects revealed robust PPI deficits in patients across "waves" (p
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- 2018
11. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis
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Wannan, Cassandra M J, primary, Nelson, Barnaby, additional, Addington, Jean, additional, Allott, Kelly, additional, Anticevic, Alan, additional, Arango, Celso, additional, Baker, Justin T, additional, Bearden, Carrie E, additional, Billah, Tashrif, additional, Bouix, Sylvain, additional, Broome, Matthew R, additional, Buccilli, Kate, additional, Cadenhead, Kristin S, additional, Calkins, Monica E, additional, Cannon, Tyrone D, additional, Cecci, Guillermo, additional, Chen, Eric Yu Hai, additional, Cho, Kang Ik K, additional, Choi, Jimmy, additional, Clark, Scott R, additional, Coleman, Michael J, additional, Conus, Philippe, additional, Corcoran, Cheryl M, additional, Cornblatt, Barbara A, additional, Diaz-Caneja, Covadonga M, additional, Dwyer, Dominic, additional, Ebdrup, Bjørn H, additional, Ellman, Lauren M, additional, Fusar-Poli, Paolo, additional, Galindo, Liliana, additional, Gaspar, Pablo A, additional, Gerber, Carla, additional, Glenthøj, Louise Birkedal, additional, Glynn, Robert, additional, Harms, Michael P, additional, Horton, Leslie E, additional, Kahn, René S, additional, Kambeitz, Joseph, additional, Kambeitz-Ilankovic, Lana, additional, Kane, John M, additional, Kapur, Tina, additional, Keshavan, Matcheri S, additional, Kim, Sung-Wan, additional, Koutsouleris, Nikolaos, additional, Kubicki, Marek, additional, Kwon, Jun Soo, additional, Langbein, Kerstin, additional, Lewandowski, Kathryn E, additional, Light, Gregory A, additional, Mamah, Daniel, additional, Marcy, Patricia J, additional, Mathalon, Daniel H, additional, McGorry, Patrick D, additional, Mittal, Vijay A, additional, Nordentoft, Merete, additional, Nunez, Angela, additional, Pasternak, Ofer, additional, Pearlson, Godfrey D, additional, Perez, Jesus, additional, Perkins, Diana O, additional, Powers, Albert R, additional, Roalf, David R, additional, Sabb, Fred W, additional, Schiffman, Jason, additional, Shah, Jai L, additional, Smesny, Stefan, additional, Spark, Jessica, additional, Stone, William S, additional, Strauss, Gregory P, additional, Tamayo, Zailyn, additional, Torous, John, additional, Upthegrove, Rachel, additional, Vangel, Mark, additional, Verma, Swapna, additional, Wang, Jijun, additional, Rossum, Inge Winter-van, additional, Wolf, Daniel H, additional, Wolff, Phillip, additional, Wood, Stephen J, additional, Yung, Alison R, additional, Agurto, Carla, additional, Alvarez-Jimenez, Mario, additional, Amminger, Paul, additional, Armando, Marco, additional, Asgari-Targhi, Ameneh, additional, Cahill, John, additional, Carrión, Ricardo E, additional, Castro, Eduardo, additional, Cetin-Karayumak, Suheyla, additional, Mallar Chakravarty, M, additional, Cho, Youngsun T, additional, Cotter, David, additional, D’Alfonso, Simon, additional, Ennis, Michaela, additional, Fadnavis, Shreyas, additional, Fonteneau, Clara, additional, Gao, Caroline, additional, Gupta, Tina, additional, Gur, Raquel E, additional, Gur, Ruben C, additional, Hamilton, Holly K, additional, Hoftman, Gil D, additional, Jacobs, Grace R, additional, Jarcho, Johanna, additional, Ji, Jie Lisa, additional, Kohler, Christian G, additional, Lalousis, Paris Alexandros, additional, Lavoie, Suzie, additional, Lepage, Martin, additional, Liebenthal, Einat, additional, Mervis, Josh, additional, Murty, Vishnu, additional, Nicholas, Spero C, additional, Ning, Lipeng, additional, Penzel, Nora, additional, Poldrack, Russell, additional, Polosecki, Pablo, additional, Pratt, Danielle N, additional, Rabin, Rachel, additional, Rahimi Eichi, Habiballah, additional, Rathi, Yogesh, additional, Reichenberg, Avraham, additional, Reinen, Jenna, additional, Rogers, Jack, additional, Ruiz-Yu, Bernalyn, additional, Scott, Isabelle, additional, Seitz-Holland, Johanna, additional, Srihari, Vinod H, additional, Srivastava, Agrima, additional, Thompson, Andrew, additional, Turetsky, Bruce I, additional, Walsh, Barbara C, additional, Whitford, Thomas, additional, Wigman, Johanna T W, additional, Yao, Beier, additional, Yuen, Hok Pan, additional, Ahmed, Uzair, additional, Byun, Andrew (Jin Soo), additional, Chung, Yoonho, additional, Do, Kim, additional, Hendricks, Larry, additional, Huynh, Kevin, additional, Jeffries, Clark, additional, Lane, Erlend, additional, Langholm, Carsten, additional, Lin, Eric, additional, Mantua, Valentina, additional, Santorelli, Gennarina, additional, Ruparel, Kosha, additional, Zoupou, Eirini, additional, Adasme, Tatiana, additional, Addamo, Lauren, additional, Adery, Laura, additional, Ali, Munaza, additional, Auther, Andrea, additional, Aversa, Samantha, additional, Baek, Seon-Hwa, additional, Bates, Kelly, additional, Bathery, Alyssa, additional, Bayer, Johanna M M, additional, Beedham, Rebecca, additional, Bilgrami, Zarina, additional, Birch, Sonia, additional, Bonoldi, Ilaria, additional, Borders, Owen, additional, Borgatti, Renato, additional, Brown, Lisa, additional, Bruna, Alejandro, additional, Carrington, Holly, additional, Castillo-Passi, Rolando I, additional, Chen, Justine, additional, Cheng, Nicholas, additional, Ching, Ann Ee, additional, Clifford, Chloe, additional, Colton, Beau-Luke, additional, Contreras, Pamela, additional, Corral, Sebastián, additional, Damiani, Stefano, additional, Done, Monica, additional, Estradé, Andrés, additional, Etuka, Brandon Asika, additional, Formica, Melanie, additional, Furlan, Rachel, additional, Geljic, Mia, additional, Germano, Carmela, additional, Getachew, Ruth, additional, Goncalves, Mathias, additional, Haidar, Anastasia, additional, Hartmann, Jessica, additional, Jo, Anna, additional, John, Omar, additional, Kerins, Sarah, additional, Kerr, Melissa, additional, Kesselring, Irena, additional, Kim, Honey, additional, Kim, Nicholas, additional, Kinney, Kyle, additional, Krcmar, Marija, additional, Kotler, Elana, additional, Lafanechere, Melanie, additional, Lee, Clarice, additional, Llerena, Joshua, additional, Markiewicz, Christopher, additional, Matnejl, Priya, additional, Maturana, Alejandro, additional, Mavambu, Aissata, additional, Mayol-Troncoso, Rocío, additional, McDonnell, Amelia, additional, McGowan, Alessia, additional, McLaughlin, Danielle, additional, McIlhenny, Rebecca, additional, McQueen, Brittany, additional, Mebrahtu, Yohannes, additional, Mensi, Martina, additional, Hui, Christy Lai Ming, additional, Suen, Yi Nam, additional, Wong, Stephanie Ming Yin, additional, Morrell, Neal, additional, Omar, Mariam, additional, Partridge, Alice, additional, Phassouliotis, Christina, additional, Pichiecchio, Anna, additional, Politi, Pierluigi, additional, Porter, Christian, additional, Provenzani, Umberto, additional, Prunier, Nicholas, additional, Raj, Jasmine, additional, Ray, Susan, additional, Rayner, Victoria, additional, Reyes, Manuel, additional, Reynolds, Kate, additional, Rush, Sage, additional, Salinas, Cesar, additional, Shetty, Jashmina, additional, Snowball, Callum, additional, Tod, Sophie, additional, Turra-Fariña, Gabriel, additional, Valle, Daniela, additional, Veale, Simone, additional, Whitson, Sarah, additional, Wickham, Alana, additional, Youn, Sarah, additional, Zamorano, Francisco, additional, Zavaglia, Elissa, additional, Zinberg, Jamie, additional, Woods, Scott W, additional, and Shenton, Martha E, additional
- Published
- 2024
- Full Text
- View/download PDF
12. Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia.
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Thomas, Michael L, Green, Michael F, Hellemann, Gerhard, Sugar, Catherine A, Tarasenko, Melissa, Calkins, Monica E, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Radant, Allen D, Seidman, Larry J, Shiluk, Alexandra L, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Braff, David L, and Light, Gregory A
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Humans ,Auditory Perceptual Disorders ,Disability Evaluation ,Cross-Sectional Studies ,Cognition Disorders ,Psychotic Disorders ,Schizophrenia ,Psychiatric Status Rating Scales ,Schizophrenic Psychology ,Contingent Negative Variation ,Models ,Psychological ,Social Behavior Disorders ,Adult ,Middle Aged ,Female ,Male ,Mental Health ,Clinical Research ,Behavioral and Social Science ,Serious Mental Illness ,Prevention ,Brain Disorders ,Neurosciences ,Mental health ,Other Medical and Health Sciences ,Psychology ,Cognitive Sciences - Abstract
ImportanceNeurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene.ObjectivesTo characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve cognition and psychosocial functioning in schizophrenia.Design, setting, and participantsCross-sectional data were analyzed using structural equation modeling to examine the associations among EAP, cognition, negative symptoms, and functional outcome. Participants were recruited from the community at 5 geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia 2 from July 1, 2010, through January 31, 2014. This well-characterized cohort of 1415 patients with schizophrenia underwent EAP, cognitive, and thorough clinical and functional assessment.Main outcome and measuresMismatch negativity, P3a, and reorienting negativity were used to measure EAP. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test-Second Edition, the Wechsler Memory Scale-Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale.ResultsParticipants included 1415 unrelated outpatients diagnosed with schizophrenia or schizoaffective disorder (mean [SD] age, 46 [11] years; 979 males [69.2%] and 619 white [43.7%]). Early auditory information processing had a direct effect on cognition (β = 0.37, P
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- 2017
13. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ):Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis
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Wannan, Cassandra M.J., Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin T., Bearden, Carrie E., Billah, Tashrif, Bouix, Sylvain, Broome, Matthew R., Buccilli, Kate, Cadenhead, Kristin S., Calkins, Monica E., Cannon, Tyrone D., Cecci, Guillermo, Chen, Eric Yu Hai, Cho, Kang Ik K., Choi, Jimmy, Clark, Scott R., Coleman, Michael J., Conus, Philippe, Corcoran, Cheryl M., Cornblatt, Barbara A., Diaz-Caneja, Covadonga M., Dwyer, Dominic, Ebdrup, Bjørn H., Ellman, Lauren M., Fusar-Poli, Paolo, Galindo, Liliana, Gaspar, Pablo A., Gerber, Carla, Glenthøj, Louise Birkedal, Glynn, Robert, Harms, Michael P., Horton, Leslie E., Kahn, René S., Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Kane, John M., Kapur, Tina, Keshavan, Matcheri S., Kim, Sung Wan, Koutsouleris, Nikolaos, Kubicki, Marek, Kwon, Jun Soo, Langbein, Kerstin, Lewandowski, Kathryn E., Light, Gregory A., Mamah, Daniel, Marcy, Patricia J., Mathalon, Daniel H., McGorry, Patrick D., Mittal, Vijay A., Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey D., Perez, Jesus, Perkins, Diana O., Powers, Albert R., Roalf, David R., Sabb, Fred W., Schiffman, Jason, Shah, Jai L., Smesny, Stefan, Spark, Jessica, Stone, William S., Strauss, Gregory P., Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge Winter van, Wolf, Daniel H., Wolff, Phillip, Wood, Stephen J., Yung, Alison R., Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo E., Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M., Cho, Youngsun T., Cotter, David, D'Alfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel E., Gur, Ruben C., Hamilton, Holly K., Hoftman, Gil D., Jacobs, Grace R., Jarcho, Johanna, Ji, Jie Lisa, Kohler, Christian G., Lalousis, Paris Alexandros, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero C., Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle N., Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod H., Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce I., Walsh, Barbara C., Whitford, Thomas, Wigman, Johanna T.W., Yao, Beier, Yuen, Hok Pan, Ahmed, Uzair, Byun, Andrew Jin Soo, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, Langholm, Carsten, Lin, Eric, Mantua, Valentina, Santorelli, Gennarina, Ruparel, Kosha, Zoupou, Eirini, Adasme, Tatiana, Addamo, Lauren, Adery, Laura, Ali, Munaza, Auther, Andrea, Aversa, Samantha, Baek, Seon Hwa, Bates, Kelly, Bathery, Alyssa, Bayer, Johanna M.M., Beedham, Rebecca, Bilgrami, Zarina, Birch, Sonia, Bonoldi, Ilaria, Borders, Owen, Borgatti, Renato, Brown, Lisa, Bruna, Alejandro, Carrington, Holly, Castillo-Passi, Rolando I., Chen, Justine, Cheng, Nicholas, Ching, Ann Ee, Clifford, Chloe, Colton, Beau Luke, Contreras, Pamela, Corral, Sebastián, Damiani, Stefano, Done, Monica, Estradé, Andrés, Etuka, Brandon Asika, Formica, Melanie, Furlan, Rachel, Geljic, Mia, Germano, Carmela, Getachew, Ruth, Goncalves, Mathias, Haidar, Anastasia, Hartmann, Jessica, Jo, Anna, John, Omar, Kerins, Sarah, Kerr, Melissa, Kesselring, Irena, Kim, Honey, Kim, Nicholas, Kinney, Kyle, Krcmar, Marija, Kotler, Elana, Lafanechere, Melanie, Lee, Clarice, Llerena, Joshua, Markiewicz, Christopher, Matnejl, Priya, Maturana, Alejandro, Mavambu, Aissata, Mayol-Troncoso, Rocío, McDonnell, Amelia, McGowan, Alessia, McLaughlin, Danielle, McIlhenny, Rebecca, McQueen, Brittany, Mebrahtu, Yohannes, Mensi, Martina, Hui, Christy Lai Ming, Suen, Yi Nam, Wong, Stephanie Ming Yin, Morrell, Neal, Omar, Mariam, Partridge, Alice, Phassouliotis, Christina, Pichiecchio, Anna, Politi, Pierluigi, Porter, Christian, Provenzani, Umberto, Prunier, Nicholas, Raj, Jasmine, Ray, Susan, Rayner, Victoria, Reyes, Manuel, Reynolds, Kate, Rush, Sage, Salinas, Cesar, Shetty, Jashmina, Snowball, Callum, Tod, Sophie, Turra-Fariña, Gabriel, Valle, Daniela, Veale, Simone, Whitson, Sarah, Wickham, Alana, Youn, Sarah, Zamorano, Francisco, Zavaglia, Elissa, Zinberg, Jamie, Woods, Scott W., Shenton, Martha E., Wannan, Cassandra M.J., Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin T., Bearden, Carrie E., Billah, Tashrif, Bouix, Sylvain, Broome, Matthew R., Buccilli, Kate, Cadenhead, Kristin S., Calkins, Monica E., Cannon, Tyrone D., Cecci, Guillermo, Chen, Eric Yu Hai, Cho, Kang Ik K., Choi, Jimmy, Clark, Scott R., Coleman, Michael J., Conus, Philippe, Corcoran, Cheryl M., Cornblatt, Barbara A., Diaz-Caneja, Covadonga M., Dwyer, Dominic, Ebdrup, Bjørn H., Ellman, Lauren M., Fusar-Poli, Paolo, Galindo, Liliana, Gaspar, Pablo A., Gerber, Carla, Glenthøj, Louise Birkedal, Glynn, Robert, Harms, Michael P., Horton, Leslie E., Kahn, René S., Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Kane, John M., Kapur, Tina, Keshavan, Matcheri S., Kim, Sung Wan, Koutsouleris, Nikolaos, Kubicki, Marek, Kwon, Jun Soo, Langbein, Kerstin, Lewandowski, Kathryn E., Light, Gregory A., Mamah, Daniel, Marcy, Patricia J., Mathalon, Daniel H., McGorry, Patrick D., Mittal, Vijay A., Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey D., Perez, Jesus, Perkins, Diana O., Powers, Albert R., Roalf, David R., Sabb, Fred W., Schiffman, Jason, Shah, Jai L., Smesny, Stefan, Spark, Jessica, Stone, William S., Strauss, Gregory P., Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge Winter van, Wolf, Daniel H., Wolff, Phillip, Wood, Stephen J., Yung, Alison R., Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo E., Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M., Cho, Youngsun T., Cotter, David, D'Alfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel E., Gur, Ruben C., Hamilton, Holly K., Hoftman, Gil D., Jacobs, Grace R., Jarcho, Johanna, Ji, Jie Lisa, Kohler, Christian G., Lalousis, Paris Alexandros, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero C., Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle N., Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod H., Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce I., Walsh, Barbara C., Whitford, Thomas, Wigman, Johanna T.W., Yao, Beier, Yuen, Hok Pan, Ahmed, Uzair, Byun, Andrew Jin Soo, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, Langholm, Carsten, Lin, Eric, Mantua, Valentina, Santorelli, Gennarina, Ruparel, Kosha, Zoupou, Eirini, Adasme, Tatiana, Addamo, Lauren, Adery, Laura, Ali, Munaza, Auther, Andrea, Aversa, Samantha, Baek, Seon Hwa, Bates, Kelly, Bathery, Alyssa, Bayer, Johanna M.M., Beedham, Rebecca, Bilgrami, Zarina, Birch, Sonia, Bonoldi, Ilaria, Borders, Owen, Borgatti, Renato, Brown, Lisa, Bruna, Alejandro, Carrington, Holly, Castillo-Passi, Rolando I., Chen, Justine, Cheng, Nicholas, Ching, Ann Ee, Clifford, Chloe, Colton, Beau Luke, Contreras, Pamela, Corral, Sebastián, Damiani, Stefano, Done, Monica, Estradé, Andrés, Etuka, Brandon Asika, Formica, Melanie, Furlan, Rachel, Geljic, Mia, Germano, Carmela, Getachew, Ruth, Goncalves, Mathias, Haidar, Anastasia, Hartmann, Jessica, Jo, Anna, John, Omar, Kerins, Sarah, Kerr, Melissa, Kesselring, Irena, Kim, Honey, Kim, Nicholas, Kinney, Kyle, Krcmar, Marija, Kotler, Elana, Lafanechere, Melanie, Lee, Clarice, Llerena, Joshua, Markiewicz, Christopher, Matnejl, Priya, Maturana, Alejandro, Mavambu, Aissata, Mayol-Troncoso, Rocío, McDonnell, Amelia, McGowan, Alessia, McLaughlin, Danielle, McIlhenny, Rebecca, McQueen, Brittany, Mebrahtu, Yohannes, Mensi, Martina, Hui, Christy Lai Ming, Suen, Yi Nam, Wong, Stephanie Ming Yin, Morrell, Neal, Omar, Mariam, Partridge, Alice, Phassouliotis, Christina, Pichiecchio, Anna, Politi, Pierluigi, Porter, Christian, Provenzani, Umberto, Prunier, Nicholas, Raj, Jasmine, Ray, Susan, Rayner, Victoria, Reyes, Manuel, Reynolds, Kate, Rush, Sage, Salinas, Cesar, Shetty, Jashmina, Snowball, Callum, Tod, Sophie, Turra-Fariña, Gabriel, Valle, Daniela, Veale, Simone, Whitson, Sarah, Wickham, Alana, Youn, Sarah, Zamorano, Francisco, Zavaglia, Elissa, Zinberg, Jamie, Woods, Scott W., and Shenton, Martha E.
- Abstract
This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals., This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
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- 2024
14. Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia
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Greenwood, Tiffany A., Swerdlow, Neal R., Sprock, Joyce, Calkins, Monica E., Freedman, Robert, Green, Michael F., Gur, Raquel E., Gur, Ruben C., Lazzeroni, Laura C., Light, Gregory A., Nuechterlein, Keith H., Radant, Allen D., Silverman, Jeremy M., Stone, William S., Sugar, Catherine A., Tsuang, Debby W., Tsuang, Ming T., Turetsky, Bruce I., Braff, David L., and Duncan, Erica
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- 2020
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15. Meta-analysis of olfactory dysfunction in 22q11.2 deletion syndrome
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Moberg, Paul J., Turetsky, Bruce I., Moberg, Emily A., Kohler, Christian G., Tang, Sunny X., Gur, Ruben C., Gur, Raquel E., and Roalf, David R.
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- 2020
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16. Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History.
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Greenwood, Tiffany A, Light, Gregory A, Swerdlow, Neal R, Calkins, Monica E, Green, Michael F, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Olincy, Ann, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Freedman, Robert, and Braff, David L
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Brain ,Humans ,Electroencephalography ,Severity of Illness Index ,Family ,Parents ,Siblings ,Schizophrenia ,Schizophrenic Psychology ,Evoked Potentials ,Adolescent ,Adult ,Aged ,Middle Aged ,Female ,Male ,Young Adult ,Endophenotypes ,Prepulse Inhibition ,Neurosciences ,Clinical Research ,Human Genome ,Brain Disorders ,Genetics ,Mental Health ,Mental health ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
ObjectiveThe Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton).MethodA total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons.ResultsBoth PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families.ConclusionsPPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures.
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- 2016
17. Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study
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Greenwood, Tiffany A, Lazzeroni, Laura C, Calkins, Monica E, Freedman, Robert, Green, Michael F, Gur, Raquel E, Gur, Ruben C, Light, Gregory A, Nuechterlein, Keith H, Olincy, Ann, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Stone, William S, Sugar, Catherine A, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Braff, David L
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Clinical Research ,Schizophrenia ,Brain Disorders ,Prevention ,Mental Health ,Human Genome ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Endophenotypes ,Family ,Genetic Predisposition to Disease ,Humans ,Reelin Protein ,Association ,Endophenotype ,Heritability ,Linkage ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation.
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- 2016
18. Attention/vigilance in schizophrenia: Performance results from a large multi-site study of the Consortium on the Genetics of Schizophrenia (COGS)
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Nuechterlein, Keith H, Green, Michael F, Calkins, Monica E, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Light, Gregory A, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Braff, David L
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Schizophrenia ,Mental Health ,Human Genome ,Clinical Research ,Neurosciences ,Genetics ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Adolescent ,Adult ,Aged ,Antipsychotic Agents ,Attention ,Endophenotypes ,Female ,Humans ,Male ,Memory ,Middle Aged ,Neuropsychological Tests ,Psychiatric Status Rating Scales ,Psychotic Disorders ,Schizophrenic Psychology ,Smoking ,Young Adult ,Endophenotype ,Continuous Performance Test ,Cognition ,Functional capacity ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
Attention/vigilance impairments are present in individuals with schizophrenia across psychotic and remitted states and in their first-degree relatives. An important question is whether deficits in attention/vigilance can be consistently and reliably measured across sites varying in many participant demographic, clinical, and functional characteristics, as needed for large-scale genetic studies of endophenotypes. We examined Continuous Performance Test (CPT) data from phase 2 of the Consortium on the Genetics of Schizophrenia (COGS-2), the largest-scale assessment of cognitive and psychophysiological endophenotypes relevant to schizophrenia. The CPT data from 2251 participants from five sites were examined. A perceptual-load vigilance task (the Degraded Stimulus CPT or DS-CPT) and a memory-load vigilance task (CPT-Identical Pairs or CPT-IP) were utilized. Schizophrenia patients performed more poorly than healthy comparison subjects (HCS) across sites, despite significant site differences in participant age, sex, education, and racial distribution. Patient-HCS differences in signal/noise discrimination (d') in the DS-CPT varied significantly across sites, but averaged a medium effect size. CPT-IP performance showed large patient-HCS differences across sites. Poor CPT performance was independent of or weakly correlated with symptom severity, but was significantly associated with lower educational achievement and functional capacity. Current smoking was associated with poorer CPT-IP d'. Patients taking both atypical and typical antipsychotic medication performed more poorly than those on no or atypical antipsychotic medications, likely reflecting their greater severity of illness. We conclude that CPT deficits in schizophrenia can be reliably detected across sites, are relatively independent of current symptom severity, and are related to functional capacity.
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- 2015
19. California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: Comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS)
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Stone, William S, Mesholam-Gately, Raquelle I, Braff, David L, Calkins, Monica E, Freedman, Robert, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Light, Gregory A, Nuechterlein, Keith H, Olincy, Ann, Radant, Allen D, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Sugar, Catherine A, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Seidman, Larry J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Serious Mental Illness ,Schizophrenia ,Brain Disorders ,Mental Health ,Genetics ,Neurosciences ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Adolescent ,Adult ,Aged ,California ,Case-Control Studies ,Cohort Studies ,Endophenotypes ,Family ,Female ,Humans ,Male ,Memory ,Short-Term ,Mental Recall ,Middle Aged ,Neuropsychological Tests ,Recognition ,Psychology ,Schizophrenic Psychology ,Speech Perception ,Verbal Learning ,Young Adult ,Endophenotype ,Verbal learning ,Memory ,California Verbal Learning Test ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded "milder" SZ phenotypes than those acquired subsequently in the COGS-2 case-control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ.
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- 2015
20. Robust differences in antisaccade performance exist between COGS schizophrenia cases and controls regardless of recruitment strategies
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Radant, Allen D, Millard, Steven P, Braff, David L, Calkins, Monica E, Dobie, Dorcas J, Freedman, Robert, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Light, Gregory A, Meichle, Sean P, Nuechterlein, Keith H, Olincy, Ann, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Stone, William S, Swerdlow, Neal R, Sugar, Catherine A, Tsuang, Ming T, Turetsky, Bruce I, and Tsuang, Debby W
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Schizophrenia ,Brain Disorders ,Mental Health ,Neurosciences ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Adult ,Aged ,Case-Control Studies ,Cohort Studies ,Endophenotypes ,Epidemiologic Research Design ,Eye Movement Measurements ,Family ,Female ,Humans ,Male ,Middle Aged ,Neuropsychological Tests ,Psychomotor Performance ,Saccades ,Schizophrenic Psychology ,Young Adult ,Antisaccade task ,Recruitment ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
The impaired ability to make correct antisaccades (i.e., antisaccade performance) is well documented among schizophrenia subjects, and researchers have successfully demonstrated that antisaccade performance is a valid schizophrenia endophenotype that is useful for genetic studies. However, it is unclear how the ascertainment biases that unavoidably result from recruitment differences in schizophrenia subjects identified in family versus case-control studies may influence patient-control differences in antisaccade performance. To assess the impact of ascertainment bias, researchers from the Consortium on the Genetics of Schizophrenia (COGS) compared antisaccade performance and antisaccade metrics (latency and gain) in schizophrenia and control subjects from COGS-1, a family-based schizophrenia study, to schizophrenia and control subjects from COGS-2, a corresponding case-control study. COGS-2 schizophrenia subjects were substantially older; had lower education status, worse psychosocial function, and more severe symptoms; and were three times more likely to be a member of a multiplex family than COGS-1 schizophrenia subjects. Despite these variations, which were likely the result of ascertainment differences (as described in the introduction to this special issue), the effect sizes of the control-schizophrenia differences in antisaccade performance were similar in both studies (Cohen's d effect size of 1.06 and 1.01 in COGS-1 and COGS-2, respectively). This suggests that, in addition to the robust, state-independent schizophrenia-related deficits described in endophenotype studies, group differences in antisaccade performance do not vary based on subject ascertainment and recruitment factors.
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- 2015
21. Verbal working memory in schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) Study: The moderating role of smoking status and antipsychotic medications
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Lee, Junghee, Green, Michael F, Calkins, Monica E, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Light, Gregory A, Nuechterlein, Keith H, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Braff, David L
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Drug Abuse (NIDA only) ,Tobacco ,Schizophrenia ,Clinical Research ,Tobacco Smoke and Health ,Substance Misuse ,Mental Health ,Serious Mental Illness ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Good Health and Well Being ,Adult ,Antipsychotic Agents ,Case-Control Studies ,Endophenotypes ,Family ,Female ,Humans ,Male ,Memory ,Short-Term ,Mental Recall ,Middle Aged ,Neuropsychological Tests ,Psychotic Disorders ,Recognition ,Psychology ,Schizophrenic Psychology ,Smoking ,Speech Perception ,Verbal Learning ,Young Adult ,Verbal working memory ,Letter-Number span ,Moderators ,Antipsychotic medication ,Letter–Number span ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
ObjectivesWorking memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia.MethodsFrom 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the letter-number span (LNS) task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the forward condition, participants repeated the letters and numbers in the order they were presented. In the reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order.ResultsSchizophrenia patients performed more poorly than controls, with a larger difference on reorder than forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment.ConclusionsResults confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke.
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- 2015
22. Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: characterization of demographic, clinical, cognitive, and functional correlates in COGS-2.
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Light, Gregory A, Swerdlow, Neal R, Thomas, Michael L, Calkins, Monica E, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Pela, Marlena, Radant, Allen D, Seidman, Larry J, Sharp, Richard F, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Braff, David L, and Turetsky, Bruce I
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Brain ,Humans ,Electroencephalography ,Acoustic Stimulation ,Feasibility Studies ,Reproducibility of Results ,Smoking ,Auditory Perception ,Schizophrenia ,Psychiatric Status Rating Scales ,Neuropsychological Tests ,Event-Related Potentials ,P300 ,Evoked Potentials ,Auditory ,Socioeconomic Factors ,Adolescent ,Adult ,Aged ,Middle Aged ,Female ,Male ,Young Adult ,Endophenotypes ,Cognition ,EEG ,Function ,Mismatch negativity ,P300 ,P3a ,Psychiatry ,Medical and Health Sciences ,Psychology and Cognitive Sciences - Abstract
Mismatch negativity (MMN) and P3a are auditory event-related potential (ERP) components that show robust deficits in schizophrenia (SZ) patients and exhibit qualities of endophenotypes, including substantial heritability, test-retest reliability, and trait-like stability. These measures also fulfill criteria for use as cognition and function-linked biomarkers in outcome studies, but have not yet been validated for use in large-scale multi-site clinical studies. This study tested the feasibility of adding MMN and P3a to the ongoing Consortium on the Genetics of Schizophrenia (COGS) study. The extent to which demographic, clinical, cognitive, and functional characteristics contribute to variability in MMN and P3a amplitudes was also examined. Participants (HCS n=824, SZ n=966) underwent testing at 5 geographically distributed COGS laboratories. Valid ERP recordings were obtained from 91% of HCS and 91% of SZ patients. Highly significant MMN (d=0.96) and P3a (d=0.93) amplitude reductions were observed in SZ patients, comparable in magnitude to those observed in single-lab studies with no appreciable differences across laboratories. Demographic characteristics accounted for 26% and 18% of the variance in MMN and P3a amplitudes, respectively. Significant relationships were observed among demographically-adjusted MMN and P3a measures and medication status as well as several clinical, cognitive, and functional characteristics of the SZ patients. This study demonstrates that MMN and P3a ERP biomarkers can be feasibly used in multi-site clinical studies. As with many clinical tests of brain function, demographic factors contribute to MMN and P3a amplitudes and should be carefully considered in future biomarker-informed clinical studies.
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- 2015
23. Factor structure and heritability of endophenotypes in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1)
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Seidman, Larry J, Hellemann, Gerhard, Nuechterlein, Keith H, Greenwood, Tiffany A, Braff, David L, Cadenhead, Kristin S, Calkins, Monica E, Freedman, Robert, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Light, Gregory A, Olincy, Ann, Radant, Allen D, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Green, Michael F
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Biomedical and Clinical Sciences ,Clinical Sciences ,Neurosciences ,Genetics ,Brain Disorders ,Clinical Research ,Schizophrenia ,Mental Health ,Mental health ,Adolescent ,Adult ,Aged ,Arousal ,Endophenotypes ,Factor Analysis ,Statistical ,Female ,Genetic Predisposition to Disease ,Humans ,Inhibition ,Psychological ,Male ,Memory ,Episodic ,Memory ,Short-Term ,Middle Aged ,Neuropsychological Tests ,Schizophrenic Psychology ,Siblings ,Visual Perception ,Young Adult ,Endophenotype ,Neurocognition ,Neurophysiology ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
BackgroundAlthough many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements.MethodsThe first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR.ResultsAnalyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction).ConclusionsNeurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia.
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- 2015
24. The utility of P300 as a schizophrenia endophenotype and predictive biomarker: clinical and socio-demographic modulators in COGS-2.
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Turetsky, Bruce I, Dress, Erich M, Braff, David L, Calkins, Monica E, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, and Light, Gregory
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Brain ,Humans ,Substance-Related Disorders ,Electroencephalography ,Prognosis ,Smoking ,Auditory Perception ,Schizophrenia ,Psychiatric Status Rating Scales ,Neuropsychological Tests ,Event-Related Potentials ,P300 ,Socioeconomic Factors ,Adult ,Middle Aged ,Female ,Male ,Endophenotypes ,Prodromal Symptoms ,Biomarkers ,Black or African American ,Biomarker ,Endophenotype ,Event-related potential ,P300 ,Prevention ,Brain Disorders ,Mental Health ,Serious Mental Illness ,Substance Abuse ,Neurosciences ,Clinical Research ,Mental health ,Good Health and Well Being ,African Americans ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 controls and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results.
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- 2015
25. Neurocognitive performance in family-based and case-control studies of schizophrenia.
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Gur, Ruben C, Braff, David L, Calkins, Monica E, Dobie, Dorcas J, Freedman, Robert, Green, Michael F, Greenwood, Tiffany A, Lazzeroni, Laura C, Light, Gregory A, Nuechterlein, Keith H, Olincy, Ann, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Swerdlow, Neal R, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Gur, Raquel E
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Humans ,Genetic Predisposition to Disease ,Case-Control Studies ,Epidemiologic Research Design ,Family ,Schizophrenia ,Neuropsychological Tests ,Schizophrenic Psychology ,Computers ,Adolescent ,Adult ,Aged ,Middle Aged ,Young Adult ,Endophenotypes ,Neurosciences ,Mental Health ,Serious Mental Illness ,Clinical Research ,Brain Disorders ,Mental health ,Neurocognition ,Family-based ,Case-control ,Ascertainment ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
BackgroundNeurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures.MethodsThe Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS.ResultsDemographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms.ConclusionsPatients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.
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- 2015
26. Reduced safety processing during aversive social conditioning in psychosis and clinical risk
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Quarmley, Megan, Gur, Ruben C., Turetsky, Bruce I., Watters, Anna J., Bilker, Warren B., Elliott, Mark A., Calkins, Monica E., Kohler, Christian G., Ruparel, Kosha, Rupert, Petra, Gur, Raquel E., and Wolf, Daniel H.
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- 2019
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27. Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study.
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Light, Gregory, Greenwood, Tiffany A, Swerdlow, Neal R, Calkins, Monica E, Freedman, Robert, Green, Michael F, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Olincy, Ann, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Sprock, Joyce, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Braff, David L
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Humans ,Genetic Predisposition to Disease ,Family ,Nuclear Family ,Psychotic Disorders ,Schizophrenia ,Adult ,Middle Aged ,Female ,Male ,Endophenotypes ,biomarkers ,cognition ,endophenotypes ,heritability ,psychosis ,schizophrenia ,Clinical Research ,Genetics ,Serious Mental Illness ,Mental Health ,Neurosciences ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
BackgroundTwin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a "heritability gap" between the diagnosis and related endophenotypes.MethodsNuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families.ResultsThe heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively.ConclusionsEndophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis.
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- 2014
28. Olfactory deficits and psychosis-spectrum symptoms in 22q11.2 deletion syndrome
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Tang, Sunny X., Moberg, Paul J., Yi, James J., Wiemken, Andrew S., Dress, Erich M., Moore, Tyler M., Calkins, Monica E., McDonald-McGinn, Donna M., Zackai, Elaine H., Emanuel, Beverly S., Gur, Ruben C., Gur, Raquel E., and Turetsky, Bruce I.
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- 2018
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29. Social aversive conditioning in youth at clinical high risk for psychosis and with psychosis: An ERP study
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Watters, Anna J., Rupert, Petra E., Wolf, Daniel H., Calkins, Monica E., Gur, Ruben C., Gur, Raquel E., and Turetsky, Bruce I.
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- 2018
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30. Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings
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Schmeidler, James, Lazzeroni, Laura C, Swerdlow, Neal R, Ferreira, Rui P, Braff, David L, Calkins, Monica E, Cadenhead, Kristin S, Freedman, Robert, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Light, Gregory A, Olincy, Ann, Nuechterlein, Keith H, Radant, Allen D, Seidman, Larry J, Siever, Larry J, Stone, William S, Sprock, Joyce, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Silverman, Jeremy M
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Biological Psychology ,Psychology ,Brain Disorders ,Schizophrenia ,Clinical Research ,Mental Health ,Genetics ,Mental health ,Adult ,Endophenotypes ,Female ,Humans ,Male ,Mutation ,Paternal Age ,Siblings ,De novo mutations ,Copy number variants ,Genetic risk ,Familial schizophrenia ,Sporadic schizophrenia ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Clinical and health psychology - Abstract
We evaluated the discrepancy of endophenotypic performance between probands with schizophrenia and unaffected siblings by paternal age at proband birth, a possible marker for de novo mutations. Pairs of schizophrenia probands and unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or neurophysiological endophenotypes previously identified as heritable. For each endophenotype, the sibling-minus-proband differences were transformed to standardized scores. Then for each pair, the average discrepancy was calculated from its standardized scores. We tested the hypothesis that the discrepancy is associated with paternal age, controlling for the number of endophenotypes shared between proband and his or her sibling, and proband age, which were both associated with paternal age. The non-significant association between the discrepancy and paternal age was in the opposite direction from the hypothesis. Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the opposite direction. Eight other endophenotypes were also in the opposite direction, but not significant. The results did not support the hypothesized association of increased differences between sibling/proband pairs with greater paternal age. A possible explanation is that the identification of heritable endophenotypes was based on samples for which schizophrenia was attributable to inherited rather than de novo/non-inherited causes.
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- 2014
31. Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS
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Swerdlow, Neal R, Light, Gregory A, Sprock, Joyce, Calkins, Monica E, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Radant, Allen D, Ray, Amrita, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, and Braff, David L
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Brain Disorders ,Schizophrenia ,Mental Health ,Neurosciences ,Genetics ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Acoustic Stimulation ,Adolescent ,Adult ,Aged ,Analysis of Variance ,Female ,Humans ,Male ,Middle Aged ,Neural Inhibition ,Psychiatric Status Rating Scales ,Schizophrenic Psychology ,Sensory Gating ,Young Adult ,Endophenotype ,Multi-site ,Prepulse inhibition ,Startle ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
BackgroundStartle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site "COGS-2" study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data.MethodsEyeblink startle was measured in carefully screened HCS and schizophrenia patients (n=1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures.Results884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p=0.0005) and sex (pschizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures.DiscussionThe COGS-2 multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia "endophenotype" of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses.
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- 2014
32. Deficient prepulse inhibition in schizophrenia in a multi-site cohort: Internal replication and extension
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Swerdlow, Neal R., Light, Gregory A., Thomas, Michael L., Sprock, Joyce, Calkins, Monica E., Green, Michael F., Greenwood, Tiffany A., Gur, Raquel E., Gur, Ruben C., Lazzeroni, Laura C., Nuechterlein, Keith H., Radant, Allen D., Seidman, Larry J., Siever, Larry J., Silverman, Jeremy M., Stone, William S., Sugar, Catherine A., Tsuang, Debby W., Tsuang, Ming T., Turetsky, Bruce I., and Braff, David L.
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- 2018
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33. Structural anomalies of the peripheral olfactory system in psychosis high-risk subjects
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Turetsky, Bruce I., Moberg, Paul J., Quarmley, Megan, Dress, Erich, Calkins, Monica E., Ruparel, Kosha, Prabhakaran, Karthik, Gur, Raquel E., and Roalf, David R.
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- 2018
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34. “It's Not What You Say, But How You Say it”: A Reciprocal Temporo-frontal Network for Affective Prosody
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Leitman, David I, Wolf, Daniel H, Ragland, J Daniel, Laukka, Petri, Loughead, James, Valdez, Jeffrey N, Javitt, Daniel C, Turetsky, Bruce I, and Gur, Ruben C
- Subjects
Clinical Research ,Behavioral and Social Science ,Mental Health ,Neurosciences ,Basic Behavioral and Social Science ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,amygdala ,auditory cortex ,emotion ,inferior frontal gyrus ,prosody ,speech ,Psychology ,Cognitive Sciences ,Experimental Psychology - Abstract
Humans communicate emotion vocally by modulating acoustic cues such as pitch, intensity and voice quality. Research has documented how the relative presence or absence of such cues alters the likelihood of perceiving an emotion, but the neural underpinnings of acoustic cue-dependent emotion perception remain obscure. Using functional magnetic resonance imaging in 20 subjects we examined a reciprocal circuit consisting of superior temporal cortex, amygdala and inferior frontal gyrus that may underlie affective prosodic comprehension. Results showed that increased saliency of emotion-specific acoustic cues was associated with increased activation in superior temporal cortex [planum temporale (PT), posterior superior temporal gyrus (pSTG), and posterior superior middle gyrus (pMTG)] and amygdala, whereas decreased saliency of acoustic cues was associated with increased inferior frontal activity and temporo-frontal connectivity. These results suggest that sensory-integrative processing is facilitated when the acoustic signal is rich in affective information, yielding increased activation in temporal cortex and amygdala. Conversely, when the acoustic signal is ambiguous, greater evaluative processes are recruited, increasing activation in inferior frontal gyrus (IFG) and IFG STG connectivity. Auditory regions may thus integrate acoustic information with amygdala input to form emotion-specific representations, which are evaluated within inferior frontal regions.
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- 2010
35. Sensitivity of Schizophrenia Endophenotype Biomarkers to Anticholinergic Medication Burden
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Joshi, Yash B., primary, Molina, Juan L., additional, Braff, David L., additional, Green, Michael F., additional, Gur, Ruben C., additional, Gur, Raquel E., additional, Nuechterlein, Keith H., additional, Stone, William S., additional, Greenwood, Tiffany A., additional, Lazzeroni, Laura C., additional, Radant, Allen D., additional, Silverman, Jeremy M., additional, Sprock, Joyce, additional, Sugar, Catherine A., additional, Tsuang, Debby W., additional, Tsuang, Ming T., additional, Turetsky, Bruce I., additional, Swerdlow, Neal R., additional, and Light, Gregory A., additional
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- 2023
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36. Inference for a Random Wavelet Packet Model of Single-Channel Event-Related Potentials
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Raz, Jonathan, Turetsky, Bruce I., and Dickerson, Linda W.
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- 2001
37. Neurocognitive Functioning in Patients with 22q11.2 Deletion Syndrome: A Meta-Analytic Review
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Moberg, Paul J., Richman, Mara J., Roalf, David R., Morse, Chelsea L., Graefe, Anna C., Brennan, Laura, Vickers, Kayci, Tsering, Wangchen, Kamath, Vidyulata, Turetsky, Bruce I., Gur, Ruben C., and Gur, Raquel E.
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- 2018
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38. Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia
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Egbujo, Chijioke N., Sinclair, Duncan, Borgmann-Winter, Karin E., Arnold, Steven E., Turetsky, Bruce I., and Hahn, Chang-Gyu
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- 2015
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39. Negative symptoms in youths with psychosis spectrum features: Complementary scales in relation to neurocognitive performance and function
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Gur, Raquel E., March, Mary, Calkins, Monica E., Weittenhiller, Lauren, Wolf, Daniel H., Turetsky, Bruce I., and Gur, Ruben C.
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- 2015
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40. Comparison of auditory and visual oddball fMRI in schizophrenia
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Collier, Azurii K., Wolf, Daniel H., Valdez, Jeffrey N., Turetsky, Bruce I., Elliott, Mark A., Gur, Raquel E., and Gur, Ruben C.
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- 2014
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41. The effect of odor valence on olfactory performance in schizophrenia patients, unaffected relatives and at-risk youth
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Kamath, Vidyulata, Turetsky, Bruce I., Calkins, Monica E., Bilker, Warren B., Frishberg, Nathan, Borgmann-Winter, Karin, Kohler, Christian G., Conroy, Catherine G., Gur, Raquel E., and Moberg, Paul J.
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- 2013
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42. Task- and resting-state functional connectivity of brain regions related to affection and susceptible to concurrent cognitive demand
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Kellermann, Tanja S., Caspers, Svenja, Fox, Peter T., Zilles, Karl, Roski, Christian, Laird, Angela R., Turetsky, Bruce I., and Eickhoff, Simon B.
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- 2013
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43. Behavioral and Physiological Findings of Gender Differences in Global-Local Visual Processing
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Roalf, David, Lowery, Natasha, and Turetsky, Bruce I.
- Abstract
Hemispheric asymmetries in global-local visual processing are well-established, as are gender differences in cognition. Although hemispheric asymmetry presumably underlies gender differences in cognition, the literature on gender differences in global-local processing is sparse. We employed event related brain potential (ERP) recordings during performance of a global-local reaction time task to compare hemispheric asymmetries and processing biases in adult men (n=15) and women (n=15). Women responded more quickly to local targets while men did not differentially respond to hierarchical stimuli. ERP data indicated that women had P100 responses that were selectively lateralized to the left hemisphere in response to local targets and N150 responses that were smaller for global targets. They also had P300 responses that were greater following local stimuli. The physiological data demonstrate that male-female performance differences arise from biologically based differences in hemispheric asymmetry. Findings are discussed in the context of existing literature regarding gender differences, hemispheric specialization, and the role of stimulus characteristics.
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- 2006
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44. Mapping genomic loci implicates genes and synaptic biology in schizophrenia
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Medical Research Council (UK), National Natural Science Foundation of China, Royal Society (UK), Chinese Academy of Sciences, Shanghai Science and Technology Committee, Research Council of Norway, European Commission, Fundação de Amparo à Pesquisa do Estado de São Paulo, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Alicia Koplowitz, Fundación Alonso Lozano, Mental Health Research UK, Wellcome Trust, Brain and Behavior Research Foundation, NIHR Biomedical Research Centre (UK), University College London, Generalitat Valenciana, Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey S., Lam, Max, Curtis, Charles, Nikitina-Zake, Liene, Davidson, Michael, Joa, Inge, Davis, Kenneth L., Yolken, Robert, Murray, Robin M., de Haan, Lieuwe, Legge, Sophie E., Serretti, Alessandro, van Os, Jim, Smoller, Jordan W., Agartz, Ingrid, Alizadeh, Behrooz Z., Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Zai, Clement C., Dikeos, Dimitris, Dinan, Timothy, Henskens, Frans A., Vaaler, Arne, Noto, Cristiano, Nimgaonkar, Vishwajit, Rautanen, Anna, Lehrer, Douglas S., Djurovic, Srdjan, Duan, Jubao, Julià, Antonio, Stahl, Eli A., Zhou, Wei, Vawter, Marquis P., Toncheva, Draga, Webb, Bradley T., Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanas Saura, Lourdes, Goldstein, Jacqueline I., Faraone, Stephen V., Lencer, Rebecca, Moreno, Carmen, Bacanu, Silviu A., Fiorentino, Alessia, Calkins, Monica E., Mitjans, Marina, Forstner, Andreas, Nuechterlein, Keith H., Frank, Josef, Tsuang, Debby W., Freimer, Nelson B., Tooney, Paul A., Belangero, Sintia Iole, Weinberger, Daniel R., Fromer, Menachem, Ge,Tian, Adolfsson, Rolf, Hakonarson, Hakon, Zhu, Feng, Frustaci, Alessandra, Nöthen, Markus M., Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Quattrone, Diego, Kähler, Anna K., Kam-Thong, Tony, van Amelsvoort, Therese, Vilella, Elisabet, Molden, Espen, O'Brien, Niamh Louise, Zimprich, Fritz, Kamatani, Yoichiro, Braun, Alice, Melegh, Bela, Pirinen, Matti, Karachanak-Yankova, Sena, Ophoff, Roel A., Kebir, Oussama, Lerer, Bernard, Nordentoft, Merete, Fanous, Ayman H., Reichenberg, Abraham, Li, Miaoxin, Periyasamy, Sathish, Lieberman, Jeffrey, Werge, Thomas, Light, Gregory A., Limborska, Svetlana, Tosato, Sarah, Liu, Chih-Min, Olincy, Ann, Magnusson, Sigurdur, Gareeva, Anna, Bressan, Rodrigo Affonseca, Lönnqvist, Jouko, Roe, Cheryl, Cheng, Wei, Athanasiu, Lavinia, Gutiérrez, Blanca, Harvey, Carol, Loughland, Carmel M., Lubinski, Jan, Luykx, Jurjen J., Lynham, Amy, Gawlik, Micha, Macek, Milan, Mackinnon, Andrew, Buxbaum, Joseph D., Tura, Gian Battista, Bromet, Evelyn J., Atbaşoğlu, Eşref Cem, Roffman, Joshua L., Magnusson, Patrik K. E., Maher, Brion S., Ota, Vanessa Kiyomi, Paciga, Sara A., Gejman, Pablo V., Arango, Celso, Forti, Marta Di, Maier, Wolfgang, Richards, Alexander L., Malaspina, Dolores, Mallet, Jacques, Metspalu, Andres, Marder, Stephen R., Li, Zhiqiang, Takahashi, Atsushi, Marsal, Sara, Kučinskiene, Zita Ausrele, Suvisaari, Jaana, Martin, Alicia R., Turetsky, Bruce I., Martorell, Lourdes, Palotie, Aarno, Mattheisen, Manuel, Baune, Bernhard T., Saka, Meram C., McCarley, Robert W., Giusti-Rodríguez, Paola, Riley, Brien P., Murphy, Kieran C., Gill, Michael, McDonald, Colm, Bruggeman, Richard, McGrath, John J., Sidorenko, Julia, Medeiros, Helena, Pantelis, Christos, Grove, Jakob, Campion, Dominique, Pato, Carlos N., Svrakic, Dragan M., Üçok, Alp, Glatt, Stephen J., Papadimitriou, George N., Khrunin, Andrey, Straub, Richard E., Parellada, Mara, Buckley, Peter F., Paunio, Tiina, Roth, Julian, Morgan, Vera A., Wildenauer, Dieter B., Ayub, Muhammad, Rothermundt, Matthias, Weiser, Mark, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veikko, Børglum, Anders D., Sanjuán, Julio, van Winkel, Ruud, González Peñas, Javier, Yu, Xin, Kim, Sung-Wan, Santoro, Marcos Leite, Benner, Christian, Ikeda, Masashi, Morley, Christopher P., Zeng, Jian, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Voloudakis, Georgios, Yue, Weihua, Seidman, Larry J., Sharp, Sally Isabel, Alptekin, Köksal, Klovins, Janis, Amin, Farooq, Bertolino, Alessandro, Shi, Jianxin, Siever, Larry J., Atkinson, Elizabeth G., Buckner, Randy L., Holmans, Peter A., Rivera, Margarita, Sigurdsson, Engilbert, González-Pinto, Ana, Sim, Kang, Skarabis, Nora, Stroup, T Scott, Slominsky, Petr, Guillin, Olivier, Wang, Shi-Heng, So, Hon-Cheong, Quested, Digby, Sobell, Janet L., Braff, David, Zhang, Wen, Bybjerg-Grauholm, Jonas, Söderman, Erik, Rujescu, Dan, Chambert, Kimberley D., Stain, Helen J., Melle, Ingrid, Carr, Vaughan J, Pocklington, Andrew J., Steen, Nils Eiel, Harwood, Janet, Steixner-Kumar, Agnes A., Gopal, Srihari, Stögmann, Elisabeth, Veijola, Juha, Watanabe, Kyoko, Sham, Pak C., Cahn, Wiepke, Bramon, Elvira, Roussos, Panos, Waddington, John, Perkins, Diana O., Pato, Michele T., Walter, Henrik, Kondratiev, Nikolay, Waterreus, Anna, Al Eissa, Mariam, Bobes, Julio, Golimbet, Vera, Black, Donald W., Als, Thomas D., Bray, Nicholas J., Breen, Gerome, Buccola, Nancy G., Sanders, Alan R., Byerley, William F., Cervilla, Jorge A., Michie, Patricia T., Pfuhlmann, Bruno, Chen, Wei J., Hong, Kyung Sue, O'Neill, F Anthony, Terao, Chikashi, Green, Michael F., Cloninger, C. Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Gülöksüz, Sinan, Freedman, Robert, Albus, Margot, Hayward, Caroline, Pietiläinen, Olli, Herms, Stefan, Hultman, Christina M., Galletly, Cherrie, Gandal, Michael J., Hahn, Eric, Konte, Bettina, Castle, David, Gennarelli, Massimo, Milani, Lili, Hougaard, David M., Hwu, Hai-Gwo, Pulver, Ann E., Jablensky, Assen V., Molina, Esther, Qin, Shengying, McCarroll, Steven A., Moran, Jennifer L., Azevedo, Maria Helena, Gur, Rachel E., Kraft, Julia, Mors, Ole, Catts, Stanley V., Lazzeroni, Laura C., Mortensen, Preben B., Streit, Fabian, Kusumawardhani, Agung, Alexander, Madeline, Godard, Stephanie, Müller-Myhsok, Bertram, Milanova, Vihra, Neil, Amanda L., Cichon, Sven, Giannitelli, Marianna, Cheung, Eric F. C., Kubo, Michiaki, Schwab, Sibylle G., Collier, David A., Williams, Nigel M., Morris, Derek W., Corvin, Aiden, Pimm, Jonathan, Curtis, David, Haroutunian, Vahram, Keller, Matthew C., Vassos, Evangelos, Hyman, Steven E., Iwata, Nakao, Jönsson, Erik G., Kahn, René S., Chan, Raymond C. K., Kennedy, James L., Shi, Yongyong, Adams, Mark, Witt, Stephanie H., Khusnutdinova, Elza, Verhage, Matthijs, Xu, Shuhua, Wu, Yang, Kirov, George, Arolt, Volker, Knowles, James A., Moltó, Maria Dolores, Krebs, Marie-Odile, Hartmann, Annette M., Nestadt, Gerald, Wormley, Brandon K., Bass, Nicholas J., Laurent-Levinson, Claudine, Lee, Jimmy, Muntané, Gerard, Porteous, David, Kuzelova-Ptackova, Hana, Lencz, Todd, Subramaniam, Mythily, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Swerdlow, Neal R., Cairns, Murray J., Malhotra, Anil K., Malhotra, Dheeraj, Iyegbe, Conrad, Mondelli, Valeria, Kim, Minsoo, Arrojo, Manuel, Landi, Stefano, McIntosh, Andrew M., Petryshen, Tracey L., Radant, Allen D., Frei, Oleksandr, Mesholam-Gately, Raquelle I., McQuillin, Andrew, Sugar, Catherine A., Menezes, Paulo Rossi, St Clair, David, Meier, Sandra, Powell, John, Chaumette, Boris, Stefansson, Hreinn, Domenici, Enrico, Bonassi, Stefano, Stefánsson, Kári, Wu, Jing Qin, Tsuang, Ming T., Myin-Germeys, Inez, Pellegrino, Renata, Visscher, Peter M., Yang, Jian, Posthuma, Danielle, Andreassen, Ole A., Koopmans, Frank, Kendler, Kenneth S., Chong, Siow Ann, Gur, Ruben C., Ehrenreich, Hannelore, Owen, Michael J., Rietschel, Marcella, Gratten, Jacob, Wray, Naomi R., Hoffmann, Per, Daly, Mark J., Szatkiewicz, Jin P., Huang, Hailiang, Nenadić, Igor, Torretta, Silvia, Escott-Price, Valentina, Neale, Benjamin M., Begemann, Martin, Thibaut, Florence, Agerbo, Esben, Rampino, Antonio, Sullivan, Patrick F., Schulze, Thomas G., Ripke, Stephan, Walters, James T. R., O'Donovan, Michael C., Kučinskas, Vaidutis, Belliveau, Richard A., Bene, Judit, Oh, Sang-Yun, Ta, Thi Minh Tam, Greenwood, Tiffany A., Howrigan, Daniel P., Rapaport, Mark H., Benyamin, Beben, Mowry, Bryan J., Giegling, Ina, Strengman, Eric, Bergen, Sarah E., Silverman, Jeremy M., Blasi, Giuseppe, Cohen, David, Stone, William S., Xu, Zhida, Lee, Phil H., Consoli, Angèle, Kelly, Brian J.., Cordeiro, Quirino, Esko, Tõnu, Costas, Javier, Medical Research Council (UK), National Natural Science Foundation of China, Royal Society (UK), Chinese Academy of Sciences, Shanghai Science and Technology Committee, Research Council of Norway, European Commission, Fundação de Amparo à Pesquisa do Estado de São Paulo, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Alicia Koplowitz, Fundación Alonso Lozano, Mental Health Research UK, Wellcome Trust, Brain and Behavior Research Foundation, NIHR Biomedical Research Centre (UK), University College London, Generalitat Valenciana, Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey S., Lam, Max, Curtis, Charles, Nikitina-Zake, Liene, Davidson, Michael, Joa, Inge, Davis, Kenneth L., Yolken, Robert, Murray, Robin M., de Haan, Lieuwe, Legge, Sophie E., Serretti, Alessandro, van Os, Jim, Smoller, Jordan W., Agartz, Ingrid, Alizadeh, Behrooz Z., Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Zai, Clement C., Dikeos, Dimitris, Dinan, Timothy, Henskens, Frans A., Vaaler, Arne, Noto, Cristiano, Nimgaonkar, Vishwajit, Rautanen, Anna, Lehrer, Douglas S., Djurovic, Srdjan, Duan, Jubao, Julià, Antonio, Stahl, Eli A., Zhou, Wei, Vawter, Marquis P., Toncheva, Draga, Webb, Bradley T., Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanas Saura, Lourdes, Goldstein, Jacqueline I., Faraone, Stephen V., Lencer, Rebecca, Moreno, Carmen, Bacanu, Silviu A., Fiorentino, Alessia, Calkins, Monica E., Mitjans, Marina, Forstner, Andreas, Nuechterlein, Keith H., Frank, Josef, Tsuang, Debby W., Freimer, Nelson B., Tooney, Paul A., Belangero, Sintia Iole, Weinberger, Daniel R., Fromer, Menachem, Ge,Tian, Adolfsson, Rolf, Hakonarson, Hakon, Zhu, Feng, Frustaci, Alessandra, Nöthen, Markus M., Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Quattrone, Diego, Kähler, Anna K., Kam-Thong, Tony, van Amelsvoort, Therese, Vilella, Elisabet, Molden, Espen, O'Brien, Niamh Louise, Zimprich, Fritz, Kamatani, Yoichiro, Braun, Alice, Melegh, Bela, Pirinen, Matti, Karachanak-Yankova, Sena, Ophoff, Roel A., Kebir, Oussama, Lerer, Bernard, Nordentoft, Merete, Fanous, Ayman H., Reichenberg, Abraham, Li, Miaoxin, Periyasamy, Sathish, Lieberman, Jeffrey, Werge, Thomas, Light, Gregory A., Limborska, Svetlana, Tosato, Sarah, Liu, Chih-Min, Olincy, Ann, Magnusson, Sigurdur, Gareeva, Anna, Bressan, Rodrigo Affonseca, Lönnqvist, Jouko, Roe, Cheryl, Cheng, Wei, Athanasiu, Lavinia, Gutiérrez, Blanca, Harvey, Carol, Loughland, Carmel M., Lubinski, Jan, Luykx, Jurjen J., Lynham, Amy, Gawlik, Micha, Macek, Milan, Mackinnon, Andrew, Buxbaum, Joseph D., Tura, Gian Battista, Bromet, Evelyn J., Atbaşoğlu, Eşref Cem, Roffman, Joshua L., Magnusson, Patrik K. E., Maher, Brion S., Ota, Vanessa Kiyomi, Paciga, Sara A., Gejman, Pablo V., Arango, Celso, Forti, Marta Di, Maier, Wolfgang, Richards, Alexander L., Malaspina, Dolores, Mallet, Jacques, Metspalu, Andres, Marder, Stephen R., Li, Zhiqiang, Takahashi, Atsushi, Marsal, Sara, Kučinskiene, Zita Ausrele, Suvisaari, Jaana, Martin, Alicia R., Turetsky, Bruce I., Martorell, Lourdes, Palotie, Aarno, Mattheisen, Manuel, Baune, Bernhard T., Saka, Meram C., McCarley, Robert W., Giusti-Rodríguez, Paola, Riley, Brien P., Murphy, Kieran C., Gill, Michael, McDonald, Colm, Bruggeman, Richard, McGrath, John J., Sidorenko, Julia, Medeiros, Helena, Pantelis, Christos, Grove, Jakob, Campion, Dominique, Pato, Carlos N., Svrakic, Dragan M., Üçok, Alp, Glatt, Stephen J., Papadimitriou, George N., Khrunin, Andrey, Straub, Richard E., Parellada, Mara, Buckley, Peter F., Paunio, Tiina, Roth, Julian, Morgan, Vera A., Wildenauer, Dieter B., Ayub, Muhammad, Rothermundt, Matthias, Weiser, Mark, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veikko, Børglum, Anders D., Sanjuán, Julio, van Winkel, Ruud, González Peñas, Javier, Yu, Xin, Kim, Sung-Wan, Santoro, Marcos Leite, Benner, Christian, Ikeda, Masashi, Morley, Christopher P., Zeng, Jian, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Voloudakis, Georgios, Yue, Weihua, Seidman, Larry J., Sharp, Sally Isabel, Alptekin, Köksal, Klovins, Janis, Amin, Farooq, Bertolino, Alessandro, Shi, Jianxin, Siever, Larry J., Atkinson, Elizabeth G., Buckner, Randy L., Holmans, Peter A., Rivera, Margarita, Sigurdsson, Engilbert, González-Pinto, Ana, Sim, Kang, Skarabis, Nora, Stroup, T Scott, Slominsky, Petr, Guillin, Olivier, Wang, Shi-Heng, So, Hon-Cheong, Quested, Digby, Sobell, Janet L., Braff, David, Zhang, Wen, Bybjerg-Grauholm, Jonas, Söderman, Erik, Rujescu, Dan, Chambert, Kimberley D., Stain, Helen J., Melle, Ingrid, Carr, Vaughan J, Pocklington, Andrew J., Steen, Nils Eiel, Harwood, Janet, Steixner-Kumar, Agnes A., Gopal, Srihari, Stögmann, Elisabeth, Veijola, Juha, Watanabe, Kyoko, Sham, Pak C., Cahn, Wiepke, Bramon, Elvira, Roussos, Panos, Waddington, John, Perkins, Diana O., Pato, Michele T., Walter, Henrik, Kondratiev, Nikolay, Waterreus, Anna, Al Eissa, Mariam, Bobes, Julio, Golimbet, Vera, Black, Donald W., Als, Thomas D., Bray, Nicholas J., Breen, Gerome, Buccola, Nancy G., Sanders, Alan R., Byerley, William F., Cervilla, Jorge A., Michie, Patricia T., Pfuhlmann, Bruno, Chen, Wei J., Hong, Kyung Sue, O'Neill, F Anthony, Terao, Chikashi, Green, Michael F., Cloninger, C. Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Gülöksüz, Sinan, Freedman, Robert, Albus, Margot, Hayward, Caroline, Pietiläinen, Olli, Herms, Stefan, Hultman, Christina M., Galletly, Cherrie, Gandal, Michael J., Hahn, Eric, Konte, Bettina, Castle, David, Gennarelli, Massimo, Milani, Lili, Hougaard, David M., Hwu, Hai-Gwo, Pulver, Ann E., Jablensky, Assen V., Molina, Esther, Qin, Shengying, McCarroll, Steven A., Moran, Jennifer L., Azevedo, Maria Helena, Gur, Rachel E., Kraft, Julia, Mors, Ole, Catts, Stanley V., Lazzeroni, Laura C., Mortensen, Preben B., Streit, Fabian, Kusumawardhani, Agung, Alexander, Madeline, Godard, Stephanie, Müller-Myhsok, Bertram, Milanova, Vihra, Neil, Amanda L., Cichon, Sven, Giannitelli, Marianna, Cheung, Eric F. C., Kubo, Michiaki, Schwab, Sibylle G., Collier, David A., Williams, Nigel M., Morris, Derek W., Corvin, Aiden, Pimm, Jonathan, Curtis, David, Haroutunian, Vahram, Keller, Matthew C., Vassos, Evangelos, Hyman, Steven E., Iwata, Nakao, Jönsson, Erik G., Kahn, René S., Chan, Raymond C. K., Kennedy, James L., Shi, Yongyong, Adams, Mark, Witt, Stephanie H., Khusnutdinova, Elza, Verhage, Matthijs, Xu, Shuhua, Wu, Yang, Kirov, George, Arolt, Volker, Knowles, James A., Moltó, Maria Dolores, Krebs, Marie-Odile, Hartmann, Annette M., Nestadt, Gerald, Wormley, Brandon K., Bass, Nicholas J., Laurent-Levinson, Claudine, Lee, Jimmy, Muntané, Gerard, Porteous, David, Kuzelova-Ptackova, Hana, Lencz, Todd, Subramaniam, Mythily, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Swerdlow, Neal R., Cairns, Murray J., Malhotra, Anil K., Malhotra, Dheeraj, Iyegbe, Conrad, Mondelli, Valeria, Kim, Minsoo, Arrojo, Manuel, Landi, Stefano, McIntosh, Andrew M., Petryshen, Tracey L., Radant, Allen D., Frei, Oleksandr, Mesholam-Gately, Raquelle I., McQuillin, Andrew, Sugar, Catherine A., Menezes, Paulo Rossi, St Clair, David, Meier, Sandra, Powell, John, Chaumette, Boris, Stefansson, Hreinn, Domenici, Enrico, Bonassi, Stefano, Stefánsson, Kári, Wu, Jing Qin, Tsuang, Ming T., Myin-Germeys, Inez, Pellegrino, Renata, Visscher, Peter M., Yang, Jian, Posthuma, Danielle, Andreassen, Ole A., Koopmans, Frank, Kendler, Kenneth S., Chong, Siow Ann, Gur, Ruben C., Ehrenreich, Hannelore, Owen, Michael J., Rietschel, Marcella, Gratten, Jacob, Wray, Naomi R., Hoffmann, Per, Daly, Mark J., Szatkiewicz, Jin P., Huang, Hailiang, Nenadić, Igor, Torretta, Silvia, Escott-Price, Valentina, Neale, Benjamin M., Begemann, Martin, Thibaut, Florence, Agerbo, Esben, Rampino, Antonio, Sullivan, Patrick F., Schulze, Thomas G., Ripke, Stephan, Walters, James T. R., O'Donovan, Michael C., Kučinskas, Vaidutis, Belliveau, Richard A., Bene, Judit, Oh, Sang-Yun, Ta, Thi Minh Tam, Greenwood, Tiffany A., Howrigan, Daniel P., Rapaport, Mark H., Benyamin, Beben, Mowry, Bryan J., Giegling, Ina, Strengman, Eric, Bergen, Sarah E., Silverman, Jeremy M., Blasi, Giuseppe, Cohen, David, Stone, William S., Xu, Zhida, Lee, Phil H., Consoli, Angèle, Kelly, Brian J.., Cordeiro, Quirino, Esko, Tõnu, and Costas, Javier
- Abstract
Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.
- Published
- 2022
45. A quantitative meta-analysis of olfactory dysfunction in mild cognitive impairment
- Author
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Roalf, David R, Moberg, Madelyn J, Turetsky, Bruce I, Brennan, Laura, Kabadi, Sushila, Wolk, David A, and Moberg, Paul J
- Published
- 2017
- Full Text
- View/download PDF
46. Phenylthiocarbamide (PTC) perception in ultra-high risk for psychosis participants who develop schizophrenia: Testing the evidence for an endophenotypic marker
- Author
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Brewer, Warrick J., Lin, Ashleigh, Moberg, Paul J., Smutzer, Gregory, Nelson, Barnaby, Yung, Alison R., Pantelis, Christos, McGorry, Patrick D., Turetsky, Bruce I., and Wood, Stephen J.
- Published
- 2012
- Full Text
- View/download PDF
47. An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis
- Author
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Kamath, Vidyulata, Moberg, Paul J., Calkins, Monica E., Borgmann-Winter, Karin, Conroy, Catherine G., Gur, Raquel E., Kohler, Christian G., and Turetsky, Bruce I.
- Published
- 2012
- Full Text
- View/download PDF
48. Crossmodal interactions in audiovisual emotion processing
- Author
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Müller, Veronika I., Cieslik, Edna C., Turetsky, Bruce I., and Eickhoff, Simon B.
- Published
- 2012
- Full Text
- View/download PDF
49. Mouse model predicts effects of smoking and varenicline on event-related potentials in humans
- Author
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Rudnick, Noam D., Strasser, Andrew A., Phillips, Jennifer M., Jepson, Christopher, Patterson, Freda, Frey, Joseph M., Turetsky, Bruce I., Lerman, Caryn, and Siegel, Steven J.
- Published
- 2010
50. Incongruence effects in crossmodal emotional integration
- Author
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Müller, Veronika I., Habel, Ute, Derntl, Birgit, Schneider, Frank, Zilles, Karl, Turetsky, Bruce I., and Eickhoff, Simon B.
- Published
- 2011
- Full Text
- View/download PDF
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