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327 results on '"Jeremy M. Silverman"'

1. Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Author: Yu-Han H. Hsu, Greta Pintacuda, Ruize Liu, Eugeniu Nacu, April Kim, Kalliopi Tsafou, Natalie Petrossian, William Crotty, Jung Min Suh, Jackson Riseman, Jacqueline M. Martin, Julia C. Biagini, Daya Mena, Joshua K.T. Ching, Edyta Malolepsza, Taibo Li, Tarjinder Singh, Tian Ge, Shawn B. Egri, Benjamin Tanenbaum, Caroline R. Stanclift, Annie M. Apffel, Steven A. Carr, Monica Schenone, Jake Jaffe, Nadine Fornelos, Hailiang Huang, Kevin C. Eggan, Kasper Lage, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Jr., Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chan, Eric Y.H. Chen, Wei Cheng, Eric FC. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O'Callaghan, Colm O'Dushlaine, F. Anthony O'Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Jordan W. Smoller, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O'Donovan, Shengying Qin, Akira Sawa, Rene Kahn, Kyung Sue Hong, Wenzhao Shi, Ming Tsuang, Masanari Itokawa, Gang Feng, Stephen J. Glatt, Xiancang Ma, Jinsong Tang, Yunfeng Ruan, Feng Zhu, Yasue Horiuchi, Byung Dae Lee, Eun-Jeong Joo, Woojae Myung, Kyooseob Ha, Hong-Hee Won, Ji Hyung Baek, Young Chul Chung, Sung-Wan Kim, Agung Kusumawardhani, Wei J. Chen, Hai-Gwo Hwu, Akitoyo Hishimoto, Ikuo Otsuka, Ichiro Sora, Tomoko Toyota, Takeo Yoshikawa, Hiroshi Kunugi, Kotaro Hattori, Sayuri Ishiwata, Shusuke Numata, Tetsuro Ohmori, Makoto Arai, Yuji Ozeki, Kumiko Fujii, Se Joo Kim, Heon-Jeong Lee, Yong Min Ahn, Se Hyun Kim, Kazufumi Akiyama, Kazutaka Shimoda, and Makoto Kinoshita
Subjects: Molecular interaction, Developmental neuroscience, Cellular neuroscience, Proteomics, Science
Abstract: Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.
Published: 2023
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2. The Association of Depressive Symptoms With Brain Volume Is Stronger Among Diabetic Elderly Carriers of the Haptoglobin 1-1 Genotype Compared to Non-carriers

Author: Abigail Livny, Michal Schnaider Beeri, Anthony Heymann, James Schmeidler, Erin Moshier, Ruth Tzukran, Galia Tsarfaty, Derek Leroith, Rachel Preiss, Laili Soleimani, Elizabeth Guerrero-Berroa, Jeremy M. Silverman, Barbara Bendlin, Andrew Levy, and Ramit Ravona-Springer
Subjects: haptoglobin genotype, type 2 diabetes, depression, brain volume, frontal lobe, white matter hyperintensities, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Aim: Depression is highly prevalent in type 2 diabetes and is associated with lower adherence to medical treatments, worse glycemic control, and increased risk for diabetes-related complications. The mechanisms underlying depression in type 2 diabetes are unclear. The haptoglobin (Hp) genotype is associated with type 2 diabetes related complications including increased risk for cerebrovascular pathology and worse cognitive performance. Its relationship with depression is unknown. We investigated the role of Hp genotype on the association of depression with brain and white matter hyperintensities (WMH) volumes.Methods: Depressive symptoms (measured with the 15-item Geriatric Depression Scale), brain MRI, and Hp genotypes, were examined in elderly subjects with type 2 diabetes [29 (13.8%) Hp 1–1 carriers and 181 (86.2%) non-carriers]. The interaction of Hp genotype with number of depressive symptoms on regional brain measures was assessed using regression analyses.Results: The significant interactions were such that in Hp 1–1 carriers but not in non-carriers, number of depressive symptoms was associated with overall frontal cortex (p = 0.01) and WMH (p = 0.04) volumes but not with middle temporal gyrus volume (p = 0.43).Conclusions: These results suggest that subjects with type 2 diabetes carrying the Hp 1–1 genotype may have higher susceptibility to depression in the context of white matter damage and frontal lobe atrophy. The mechanisms underlying depression in diabetes may differ by Hp genotype.
Published: 2019
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3. Decreased Motor Function Is Associated with Poorer Cognitive Function in Elderly with Type 2 Diabetes

Author: Elizabeth Guerrero-Berroa, Ramit Ravona-Springer, Anthony Heymann, James Schmeidler, Jeremy M. Silverman, Mary Sano, Keren Koifmann, Rachel Preiss, Hadas Hoffman, and Michal Schnaider Beeri
Subjects: Elderly, Memory, Dementia, Cognition, Type 2 diabetes, Motor function, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Background/Aims: Impaired motor function has been associated with cognitive impairment and dementia, but this relationship is poorly understood in elderly with type 2 diabetes (T2D). We thus investigated it in a large sample (n = 726) of cognitively normal elderly with T2D. Methods: In this cross-sectional study, hierarchical linear regressions assessed correlations of 3 motor measures (timed walk, grip strength, and self-reported motor difficulties) with episodic memory, attention/working memory, semantic categorization, executive function, and overall cognition controlling for demographics. Results: Longer timed walk and weaker grip strength were associated with poorer performance in all cognitive domains except episodic memory. Conclusions: Associations of motor and cognitive functions in T2D and non-T2D samples are consistent. A lack of association of motor function with episodic memory may suggest non-Alzheimer's disease-related underlying mechanisms.
Published: 2014
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4. The effects of age and sex on cognitive impairment in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS) study.

Author: Junghee Lee, Michael F Green, Keith H Nuechterlein, Neal R Swerdlow, Tiffany A Greenwood, Gerhard S Hellemann, Laura C Lazzeroni, Gregory A Light, Allen D Radant, Larry J Seidman, Larry J Siever, Jeremy M Silverman, Joyce Sprock, William S Stone, Catherine A Sugar, Debby W Tsuang, Ming T Tsuang, Bruce I Turetsky, Ruben C Gur, Raquel E Gur, and David L Braff
Subjects: Medicine, Science
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.
Published: 2020
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5. Sensitivity of Schizophrenia Endophenotype Biomarkers to Anticholinergic Medication Burden

Author: Yash B. Joshi, Juan L. Molina, David L. Braff, Michael F. Green, Ruben C. Gur, Raquel E. Gur, Keith H. Nuechterlein, William S. Stone, Tiffany A. Greenwood, Laura C. Lazzeroni, Allen D. Radant, Jeremy M. Silverman, Joyce Sprock, Catherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Neal R. Swerdlow, and Gregory A. Light
Subjects: Psychiatry and Mental health
Published: 2023

6. Genome-wide DNA methylation profiling in nonagenarians suggests an effect of PM20D1 in late onset Alzheimer’s disease

Author: Carolina Coto-Vílchez, José J. Martínez-Magaña, Lara Mora-Villalobos, Daniel Valerio, Alma D. Genis-Mendoza, Jeremy M. Silverman, Humberto Nicolini, Henriette Raventós, and Gabriela Chavarria-Soley
Subjects: Psychiatry and Mental health, Neurology (clinical)
Abstract: BackgroundThe aim of this study is to identify differentially methylated regions (DMRs) in the genomes of a sample of cognitively healthy individuals and a sample of individuals with LOAD, all of them nonagenarians from Costa Rica.MethodsIn this study, we compared whole blood DNA methylation profiles of 32 individuals: 21 cognitively healthy and 11 with LOAD, using the Infinium MethylationEPIC BeadChip. First, we calculated the epigenetic age of the participants based on Horvath’s epigenetic clock. DMRcate and Bumphunter were used to identify DMRs. After in silico and knowledge-based filtering of the DMRs, we performed a methylation quantitative loci (mQTL) analysis (rs708727 and rs960603).ResultsOn average, the epigenetic age was 73 years in both groups, which represents a difference of over 20 years between epigenetic and chronological age in both affected and unaffected individuals. Methylation analysis revealed 11 DMRs between groups, which contain six genes and two pseudogenes. These genes are involved in cell cycle regulation, embryogenesis, synthesis of ceramides, and migration of interneurons to the cerebral cortex. One of the six genes is PM20D1, for which altered expression has been reported in LOAD. After genotyping previously reported mQTL SNPs for the gene, we found that average methylation in the PM20D1 DMR differs between genotypes for rs708727, but not for rs960603.ConclusionsThis work supports the possible role of PM20D1 in protection against AD, by showing differential methylation in blood of affected and unaffected nonagenarians. Our results also support the influence of genetic factors on PM20D1 methylation levels.
Published: 2021

7. Anticholinergic Medication Burden–Associated Cognitive Impairment in Schizophrenia

Author: Joyce Sprock, Debby W. Tsuang, Raquel E. Gur, Yash B. Joshi, Catherine A. Sugar, Laura C. Lazzeroni, Allen D. Radant, William S. Stone, Neal R. Swerdlow, Ming T. Tsuang, David L. Braff, Keith H. Nuechterlein, Bruce I. Turetsky, Michael F. Green, Juan L. Molina, Laura R MacDonald, Michael L. Thomas, Ruben C. Gur, Gregory A. Light, Tiffany A. Greenwood, Jeremy M. Silverman, and John Nungaray
Subjects: Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Neuropsychological Tests, Article, Cholinergic Antagonists, Cohort Studies, Young Adult, 03 medical and health sciences, Cognition, 0302 clinical medicine, mental disorders, medicine, Anticholinergic, Humans, Dementia, Cognitive Dysfunction, Psychiatry, Cognitive impairment, Aged, integumentary system, business.industry, Healthy subjects, food and beverages, Middle Aged, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, Schizophrenia, lipids (amino acids, peptides, and proteins), Psychopharmacology, business, 030217 neurology & neurosurgery
Abstract: OBJECTIVE: Many 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. METHODS: Cross-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). RESULTS: ACB 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. CONCLUSIONS: Anticholinergic 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.
Published: 2021

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

Author: Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tõnu Esko, Lili Milani, Erik G. Jönsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo V. Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, José Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Müller-Myhsok, Beata Świątkowska, Thomas G. Schulze, Markus M. Nöthen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stéphane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O’Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landén, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret I. Boomsma, Brenda W.J.H. Penninx, Jouke-Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Völker, Steven P. Hamilton, Patrik K.E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Børglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein, Stephan Ripke, Benjamin M. Neale, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Sandra Meier, Carin J. Meijer, Bela Melegh, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Vihra Milanova, Younes Mokrab, Derek W. Morris, Kieran C. Murphy, Inez Myin-Germeys, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Ulrich Schall, Christian R. Schubert, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Douglas H.R. Blackwood, Ariel Darvasi, Enrico Domenici, Michael Gill, Hugh Gurling, Christina M. Hultman, Assen V. Jablensky, Kenneth S. Kendler, Jo Knight, Qingqin S. Li, Jianjun Liu, Steven A. McCarroll, Jennifer L. Moran, Michael J. Owen, Carlos N. Pato, Danielle Posthuma, Pamela Sklar, Jens R. Wendland, Mark J. Daly, Michael C. O’Donovan, Peter Donnelly, Ines Barroso, Jenefer M. Blackwell, Matthew A. Brown, Juan P. Casas, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Gavin Band, Céline Bellenguez, Colin Freeman, Eleni Giannoulatou, Garrett Hellenthal, Richard Pearson, Matti Pirinen, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Sarah Edkins, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E. Hunt, Alagurevathi Jayakumar, Jennifer Liddle, Owen T. McCann, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Mark I. McCarthy, Maria J. Arranz, Steven Bakker, Stephan Bender, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Stephen Lawrie, Kuang Lin, Don H. Linszen, Ignacio Mata, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Vassily Trubetskoy, Yunpeng Wang, Jonathan R.I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead Pavlides, Maciej Trzaskowski, Enda M. Byrne, Liam Abbott, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, Miquel Casas, Felecia Cerrato, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Claire Churchhouse, Toni-Kim Clarke, William Coryell, David W. Craig, Cristiana Cruceanu, Piotr M. Czerski, Anders M. Dale, Simone de Jong, Jurgen Del-Favero, J. Raymond DePaulo, Amanda L. Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Chun Chieh Fan, Sascha B. Fischer, Matthew Flickinger, Tatiana M. Foroud, Liz Forty, Christine Fraser, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Melissa J. Green, Tiffany A. Greenwood, Weihua Guan, Martin Hautzinger, Urs Heilbronner, Maria Hipolito, Dominic Holland, Laura Huckins, Jessica S. Johnson, Radhika Kandaswamy, Robert Karlsson, Sarah Kittel-Schneider, Anna C. Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William B. Lawson, Markus Leber, Phil H. Lee, Shawn E. Levy, Jun Z. Li, Chunyu Liu, Anna Maaser, Donald J. MacIntyre, Pamela B. Mahon, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G. McInnis, James D. McKay, Helena Medeiros, Sarah E. Medland, Fan Meng, Grant W. Montgomery, Thomas W. Mühleisen, Hoang Nguyen, Caroline M. Nievergelt, Annelie Nordin Adolfsson, Evaristus A. Nwulia, Claire O'Donovan, Loes M. Olde Loohuis, Anil P.S. Ori, Lilijana Oruc, Urban Ösby, Amy Perry, Andrea Pfennig, Eline J. Regeer, Céline S. Reinbold, John P. Rice, Fabio Rivas, Margarita Rivera, Euijung Ryu, Cristina Sánchez-Mora, Alan F. Schatzberg, William A. Scheftner, Nicholas J. Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Christine Søholm Hansen, Anne T. Spijker, Michael Steffens, John S. Strauss, Szabolcs Szelinger, Robert C. Thompson, Thorgeir E. Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J. Watson, Thomas W. Weickert, Simon Xi, Wei Xu, Allan H. Young, Peter Zandi, Peng Zhang, Sebastian Zöllner, Abdel Abdellaoui, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Fernando S. Goes, Lynsey S. Hall, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Christel M. Middeldorp, Evelin Mihailov, Francis M. Mondimore, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Jodie N. Painter, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Katherine E. Tansey, Henning Teismann, Wesley Thompson, Pippa A. Thomson, Matthew Traylor, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Shantel Marie Weinsheimer, Jürgen Wellmann, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Klaus Berger, Udo Dannlowski, Katharina Domschke, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Pamela AF. Madden, Patrik K. Magnusson, Preben Bo Mortensen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, David J. Porteous, Catherine Schaefer, Henry Völzke, Marco Bortolato, Janita Bralten, Cynthia M. Bulik, Christie L. Burton, Caitlin E. Carey, Lea K. Davis, Laramie E. Duncan, Howard J. Edenberg, Lauren Erdman, Stephen V. Faraone, Slavina B. Goleva, Wei Guo, Christopher Hübel, Laura M. Huckins, Ekaterina A. Khramtsova, Joanna Martin, Carol A. Mathews, Elise Robinson, Eli Stahl, Barbara E. Stranger, Michela Traglia, Raymond K. Walters, Lauren A. Weiss, Stacey J. Winham, Yin Yao, Kristjar Skajaa, Markus Nöthen, Michael Owen, Robert H. Yolken, Niels Plath, Jonathan Mill, Daniel Geschwind, Psychiatry 1, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Functional Genomics, Biological Psychology, APH - Mental Health, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Blokland, Gabriella AM, Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Lee, Sang Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Male, Bipolar Disorder, Schizophrenia/genetics, LD SCORE REGRESSION, Genome-wide association study, 0302 clinical medicine, Receptors, SCHIZOPHRENIA, Psychotic Disorders/genetics, KYNURENINE PATHWAY METABOLISM, Genetics, RISK, Sex Characteristics, Vascular Endothelial Growth Factor, Bipolar Disorder/genetics, Major/genetics, Single Nucleotide, AFFECTIVE STIMULI IMPACT, Schizophrenia, Sulfurtransferases, Major depressive disorder, Female, Depressive Disorder, Major/genetics, Bipolar disorder, Locus (genetics), Genomics, Biology, Polymorphism, Single Nucleotide, Article, DYSPHORIC MOOD, 03 medical and health sciences, Sex differences, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Polymorphism, GENOME-WIDE ASSOCIATION, Genotype-by-sex interaction, Biological Psychiatry, Depressive Disorder, Major, Depressive Disorder, GENDER-DIFFERENCES, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], PARAVENTRICULAR NUCLEUS, 3112 Neurosciences, Endothelial Cells, MAJOR DEPRESSION, medicine.disease, Genetic architecture, 030104 developmental biology, Mood, Receptors, Vascular Endothelial Growth Factor, Psychotic Disorders, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Published: 2022

9. Cingulate and temporal lobe fractional anisotropy in schizotypal personality disorder.

Author: Erin A. Hazlett, Kim E. Goldstein, Kazuhiro Tajima-Pozo, Elizabeth R. Speidel, Yuliya Zelmanova, Jonathan J. Entis, Jeremy M. Silverman, Antonia S. New, Harold W. Koenigsberg, M. Mehmet Haznedar, William Byne, and Larry J. Siever
Published: 2011
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10. Vitamin E Intake Is Associated with Lower Brain Volume in Haptoglobin 1-1 Elderly with Type 2 Diabetes

Author: Laili Soleimani, Jeremy M. Silverman, Andrew P. Levy, Mary Mamistalov, Ramit Ravona-Springer, Derek LeRoith, Rachel Preiss, Barbara B. Bendlin, Danit-Rivka Shahar, Anthony Heymann, Abigail Livny, Yuval Berman, Erin Moshier, Michal Schnaider Beeri, and Galia Tsarfaty
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Middle temporal gyrus, medicine.medical_treatment, Inferior frontal gyrus, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Genotype, medicine, Humans, Vitamin E, Longitudinal Studies, Aged, Haptoglobins, biology, business.industry, General Neuroscience, Haptoglobin, Brain, Organ Size, General Medicine, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Brain size, biology.protein, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: Backgrounds The efficacy of vitamin E in prevention of diabetes-related complications differs by Haptoglobin (Hp) genotype. Objective To examine the role of Hp genotype in the relationship of vitamin E intake with brain volume in cognitively normal elderly patients with type 2 diabetes. Methods Brain volumes for the superior, middle, and inferior frontal gyri and for the middle temporal gyrus were generated from structural T1 MRI in 181 study participants (Hp 1-1: n = 24, Hp 2-1: n = 77, Hp 2-2: n = 80). Daily vitamin E intake was assessed using the Food Frequency Questionnaire. Analyses of covariance, controlling for demographic and cardiovascular variables was used to evaluate whether the association of daily vitamin E intake with brain volume was modified by Hp genotype. Results Average age was 70.8 (SD = 4.2) with 40% females, and mean Mini-Mental State Examination score of 28.17 (SD = 1.90). A significant interaction was found between vitamin E intake and Hp genotype in inferior frontal gyrus' volume; p = 0.0108. For every 1 microgram increase in vitamin E intake, the volume of the inferior frontal gyrus decreased by 0.955% for Hp 1-1 (p = 0.0348), increased by 0.429% for Hp 2-1 (p = 0.0457), and by 0.077% for Hp 2-2 (p = 0.6318). There were no significant interactions between vitamin E intake and Hp genotype for the middle (p = 0.6011) and superior (p = 0.2025) frontal gyri or for the middle temporal gyrus (p = 0.503). Conclusions The effect of dietary vitamin E on the brain may differ by Hp genotype. Studies examining the impact of vitamin E on brain-related outcomes should consider Hp genotype.
Published: 2020

11. Does Computerized Cognitive Training Improve Diabetes Self-Management and Cognition? A Randomized Control Trial of Middle-Aged and Older Veterans with Type 2 Diabetes

Author: Jeremy M. Silverman, Carolyn W. Zhu, James Schmeidler, Pearl G. Lee, Neil B. Alexander, Elizabeth Guerrero-Berroa, Michal S. Beeri, Rebecca K. West, Mary Sano, Martina Nabozny, and Martha Karran
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: 1.This randomized control trial compared an adaptive computerized cognitive training intervention with a non-adaptive version. The primary hypothesis predicted better diabetes self-management in type 2 diabetes patients at 6 months post-intervention than baseline, with seven secondary outcomes. 2.Intent-to-treat analysis of veterans without dementia aged 55+ from the Bronx, NY and Ann Arbor, MI (N=90/per arm) used linear mixed model analyses. 3.Contrary to the hypothesis, only memory showed more improvement in the adaptive arm (p0.01). Post-hoc analyses combined the two arms; self-management improved at six-months post-intervention (p0.001). Memory, executive functions/attention, prospective memory, diastolic blood pressure, and systolic blood pressure improved (p0.05); hemoglobin A1c and medication adherence did not improve significantly. 4.The adaptive computerized cognitive training was not substantially better than non-adaptive, but may improve memory. Post-hoc results for the combined arms suggest computer-related activities may improve diabetes self-management and other outcomes for middle-aged and older patients with type 2 diabetes. Practice effects or awareness of being studied cannot be ruled out.
Published: 2021

12. Short-term computerized cognitive training does not improve cognition compared to an active control in non-demented adults aged 80 years and above

Author: Laura A. Rabin, Mary Sano, Jeremy M. Silverman, Michal Schnaider Beeri, Erin Moshier, and Rebecca K. West
Subjects: Male, Gerontology, Population, 03 medical and health sciences, Cognition, 0302 clinical medicine, Memory, medicine, Humans, Dementia, Attention, Cognitive Dysfunction, Cognitive skill, Neuropsychological assessment, Cognitive decline, education, Aged, 80 and over, education.field_of_study, 030214 geriatrics, medicine.diagnostic_test, Neuropsychology, Mental Status and Dementia Tests, medicine.disease, Cognitive training, Psychiatry and Mental health, Clinical Psychology, Treatment Outcome, Therapy, Computer-Assisted, Linear Models, Female, Geriatrics and Gerontology, Psychology, 030217 neurology & neurosurgery
Abstract: Background:Older adults, especially those above age 80, are the fastest growing segment of the population in the United States and at risk for age-related cognitive decline and dementia. There is growing evidence that cognitive activity and training may allow adults to maintain or improve cognitive functioning, but little is known about the potential benefit in the oldest old. In this randomized trial, the effectiveness of a computerized cognitive training program (CCT program) was compared to an active control games program to improve cognition in cognitively normal individuals aged 80 and older.Methods:Sixty-nine older adults were randomized to a 24-session CCT program (n= 39) or an active control program (n= 30). Participants completed a pre- and post- training neuropsychological assessment. The primary outcome measure was a global cognitive composite, and the secondary outcomes were the scores on specific cognitive domains (of memory, executive function/attention, and language).Results:Using linear mixed models, there were no significant differences between the CCT and the active control program on the primary (p= 0.662) or any of the secondary outcomes (language functioning,p= .628; attention/executive functioning,p= .428; memory,p= .749).Conclusion:This study suggests that short-term CCT had no specific benefit for cognitive functioning in non-demented individuals aged 80 and older.
Published: 2019

13. Distinct age-related associations for body mass index and cognition in cognitively healthy very old veterans

Author: Jeremy M. Silverman, Michal Schnaider Beeri, James Schmeidler, Clive Rosendorff, and Cecilia N Mastrogiacomo
Subjects: Male, Aging, Neuropsychological Tests, Article, Body Mass Index, Executive Function, 03 medical and health sciences, Cognition, 0302 clinical medicine, Memory, Risk Factors, Age related, medicine, Humans, Dementia, Attention, Cognitive Dysfunction, Cognitive decline, Risk factor, Association (psychology), Aged, Language, Veterans, Aged, 80 and over, 030214 geriatrics, business.industry, medicine.disease, Executive functions, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Regression Analysis, Female, Geriatrics and Gerontology, business, Gerontology, Body mass index, 030217 neurology & neurosurgery, Demography
Abstract: Associations between high body mass index (BMI) and subsequent cognitive decline, reported in elderly averaging below age 75, become less consistent at older ages. We compared the associations of BMI with cognition in moderately old (ages 75–84, N = 154) and oldest-old (85+, N = 93) samples. BMI and cognition were assessed cross-sectionally in cognitively intact elderly (mean age = 84.5, SD = 4.4) male veterans. Regression analyses of three cognitive domains — executive functions/language, attention, and memory—compared relationship with BMI between the moderately old and oldest-old. Higher BMI was associated with relatively poorer executive functions/language performance in the moderately old, while the opposite relationship, higher BMI associated with relatively better performance, was found in the oldest-old. Associations for the other two cognitive domains did not differ significantly between age groups. The reversal of association direction for executive functions/language performance with higher BMI is consistent with the protected survivor model. This model posits a minority subpopulation with a protective factor—genetic or otherwise—against both mortality and cognitive decline associated with risk factor status. The very old who remain cognitively intact despite the presence of risk factors are more likely to possess protection.
Published: 2019

14. Associations of hemoglobin A1c with cognition reduced for long diabetes duration

Author: Michal Schnaider Beeri, James Schmeidler, Neil B. Alexander, Mary Sano, Pearl G. Lee, Jeremy M. Silverman, Rebecca K. West, Martina Nabozny, Carolina Rodriguez Alvarez, and Elizabeth Guerrero-Berroa
Subjects: 0301 basic medicine, Diabetes duration, Type 2 diabetes, Protected survivor, 03 medical and health sciences, 0302 clinical medicine, Time at risk, medicine, Risk factor, 10. No inequality, Association (psychology), business.industry, Cognition, Featured Article, medicine.disease, Executive functions, Psychiatry and Mental health, Protective factors, 030104 developmental biology, Risk factors, Hemoglobin A1c, Cognitive function, Neurology (clinical), Hemoglobin, business, 030217 neurology & neurosurgery, Demography
Abstract: Introduction Associations of some risk factors with poor cognition, identified prior to age 75, are reduced or reversed in very old age. The Protected Survivor Model predicts this interaction due to enhanced survival of those with extended risk factor duration. In a younger sample, this study examines the association of cognition with the mean hemoglobin A1c risk factor over the time at risk, according to its duration. Methods The interaction of mean hemoglobin A1c (average = 9.8%), evaluated over duration (average = 116.8 months), was examined for overall cognition and three cognitive domains in a sample of 150 “young-old” veterans (mean age = 70) with type 2 diabetes. Results The predicted interactions were significant for overall cognition and attention, but not executive functions/language and memory. Discussion Findings extend the Protected Survivor Model to a “young-old” sample, from the very old. This model suggests focusing on individuals with good cognition despite prolonged high risk when seeking protective factors.
Published: 2019

15. Depression is more strongly associated with cognition in elderly women than men with type 2 diabetes

Author: Ramit Ravona-Springer, Rachel Preiss, Jeremy M. Silverman, Mary Sano, Michal Schnaider Beeri, James Schmeidler, Elizabeth Guerrero-Berroa, Laili Soleimani, Ruth Zukran, and Anthony Heymann
Subjects: 030214 geriatrics, business.industry, Cognition, Article, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 0302 clinical medicine, Categorization, Medicine, Geriatric Depression Scale, Effects of sleep deprivation on cognitive performance, Geriatrics and Gerontology, Cognitive decline, business, Gerontology, Episodic memory, 030217 neurology & neurosurgery, Depression (differential diagnoses), Management of depression, Clinical psychology
Abstract: OBJECTIVE: Depression and cognitive impairment are highly prevalent in type 2 diabetes (T2D) yet little is known about how their relationship varies by sex. DESIGN: Population-based cross-sectional study. SETTING: Community. PARTICIPANTS: Eight hundred and ninety seven non-demented elderly with type 2 diabetes aged ≥ 65 participating in the Israel Diabetes and Cognitive Decline (IDCD) Study. MEASUREMENTS: Cognition was evaluated by a comprehensive neuropsychological battery and depressive symptoms were assessed by the Geriatric Depression Scale (GDS). RESULTS: In all but the executive function domain, the association of depressive symptoms with poorer cognitive function was stronger in women than men, with a significant interaction for language/semantic categorization and missed significance for episodic memory. Using a cutoff of GDS≥ 6 for clinical depression, women with depression had significantly poorer language/semantic categorization, memory and overall cognitive function. Inclusion of anti-depressants in the model did not alter substantively the associations. CONCLUSION: Our results suggest that depressed T2D women may have poorer cognitive performance, highlighting the significance of sex-specific personalized management of depression in elderly diabetics.
Published: 2018

16. A Comparison of Ten Polygenic Score Methods for Psychiatric Disorders Applied Across Multiple Cohorts

Author: Guiyan Ni, Jian Zeng, Joana A. Revez, Ying Wang, Zhili Zheng, Tian Ge, Restuadi Restuadi, Jacqueline Kiewa, Dale R. Nyholt, Jonathan R.I. Coleman, Jordan W. Smoller, Jian Yang, Peter M. Visscher, Naomi R. Wray, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Psychosis Endophenotypes International Consortium, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Kari Stefansson, Wellcome Trust Case-Control Consortium, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O’Donovan, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Héléna A. Gaspar, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Paul F. O’Reilly, Hogni Oskarsson, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, John P. Rice, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Fabian Streit, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Yunpeng Wang, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Katharina Domschke, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Nicholas G. Martin, Preben Bo Mortensen, Merete Nordentoft, Sara A. Paciga, Nancy L. Pedersen, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Ni, Guiyan, Zeng, Jian, Revez, Joana A., Wang, Ying, Zhili, Zheng, Ge, Tian, Restuadi, Restuadi, Kiewa, Jacqueline, Nyholt, Dale R, Coleman, Jonathan RI, Smoller, Jordan W, Lee, S Hong, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Econometrics, Psychiatry, Department of Technology and Operations Management, Child and Adolescent Psychiatry / Psychology, Epidemiology, Erasmus MC other, Urology, Internal Medicine, Medical Informatics, Immunology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Multifactorial Inheritance, medicine.medical_specialty, LDpred2, BF, Genomics, Disease, Major depressive disorder, risk prediction, 03 medical and health sciences, 0302 clinical medicine, MegaPRS, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Genetic risk, Psychiatry, Biological Psychiatry, Genetic association, Depressive Disorder, Major, business.industry, Mental Disorders, medicine.disease, Genetic architecture, Polygenic scores, Risk prediction, polygenic scores, PRS-CS, psychiatric disorders, 030104 developmental biology, SBayesR, Schizophrenia, Cohort, Lassosum, RC0321, business, Psychiatric disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BACKGROUND: Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies. PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.METHODS: The Psychiatric Genomics Consortium Working Groups for schizophrenia and major depressive disorder bring together many independently collected case-control cohorts. We used these resources (31,328 schizophrenia cases, 41,191 controls; 248,750 major depressive disorder cases, 563,184 controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and 9 methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) were compared.RESULTS: Compared with PC+T, the other 9 methods gave higher prediction statistics, MegaPRS, LDPred2, and SBayesR significantly so, explaining up to 9.2% variance in liability for schizophrenia across 30 target cohorts, an increase of 44%. For major depressive disorder across 26 target cohorts, these statistics were 3.5% and 59%, respectively.CONCLUSIONS: Although the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparisons and are recommended in applications to psychiatric disorders.
Published: 2021

17. Depression and the apathy symptom are associated with poorer cognitive functioning in very old men

Author: Rebecca K. West, Barry Reisberg, Halima Suleiman, Jeremy M. Silverman, Ruby S. C. Phillips, James Schmeidler, Julia Muallem, Mary Sano, and Elizabeth Guerrero-Berroa
Subjects: Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Apathy, Neurology (clinical), Cognitive skill, Geriatrics and Gerontology, medicine.symptom, business, Depression (differential diagnoses), Clinical psychology
Published: 2020

18. Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia

Author: Allen D. Radant, William S. Stone, Debby W. Tsuang, Laura C. Lazzeroni, Raquel E. Gur, Neal R. Swerdlow, Michael F. Green, Monica E. Calkins, Ming T. Tsuang, David L. Braff, Erica Duncan, Keith H. Nuechterlein, Robert Freedman, Ruben C. Gur, Jeremy M. Silverman, Catherine A. Sugar, Bruce I. Turetsky, Joyce Sprock, Tiffany A. Greenwood, and Gregory A. Light
Subjects: Proband, Reflex, Startle, Stimulus (physiology), behavioral disciplines and activities, Article, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Biological Psychiatry, Prepulse inhibition, Genetics, Analysis of covariance, business.industry, Prepulse Inhibition, Acoustics, Heritability, 030227 psychiatry, Psychiatry and Mental health, Acoustic Stimulation, Endophenotype, Acoustic Startle Reflex, Cohort, Schizophrenia, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Latency 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. METHODS: Schizophrenia 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 120ms 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. RESULTS: 980 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
Published: 2020

19. The effects of age and sex on cognitive impairment in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS) study

Author: Allen D. Radant, Catherine A. Sugar, William S. Stone, Tiffany A. Greenwood, Debby W. Tsuang, Michael F. Green, Laura C. Lazzeroni, Bruce I. Turetsky, Larry J. Siever, David L. Braff, Gregory A. Light, Raquel E. Gur, Neal R. Swerdlow, Ming T. Tsuang, Jeremy M. Silverman, Keith H. Nuechterlein, Ruben C. Gur, Larry J. Seidman, Junghee Lee, Joyce Sprock, Gerhard Hellemann, and Hashimoto, Kenji
Subjects: Male, Emotions, Social Sciences, Neuropsychological Tests, Cognition, Learning and Memory, 0302 clinical medicine, Medicine and Health Sciences, Psychology, 2.1 Biological and endogenous factors, Aetiology, media_common, Cognitive Impairment, Genetics, Multidisciplinary, California Verbal Learning Test, Cognitive Neurology, Age Factors, Middle Aged, Memory, Short-Term, Mental Health, Neurology, Medicine, Schizophrenic Psychology, Female, Anatomy, Research Article, Vigilance (psychology), Adult, Elementary cognitive task, General Science & Technology, Cognitive Neuroscience, Science, media_common.quotation_subject, Face Recognition, Basic Behavioral and Social Science, behavioral disciplines and activities, 03 medical and health sciences, Young Adult, Sex Factors, Clinical Research, Memory, Mental Health and Psychiatry, Behavioral and Social Science, Reaction Time, Humans, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, Aged, General linear model, Working memory, Cognitive Psychology, Neurosciences, Biology and Life Sciences, Brain Disorders, 030227 psychiatry, Short-Term, Face, Case-Control Studies, Schizophrenia, Linear Models, Cognitive Science, Perception, Verbal memory, Head, 030217 neurology & neurosurgery, Neuroscience
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.
Published: 2020

20. Genome-wide Association of Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia (COGS) Study

Author: Bruce I. Turetsky, Larry J. Siever, Catherine A. Sugar, David L. Braff, Tiffany A. Greenwood, Debby W. Tsuang, Gregory A. Light, Jeremy M. Silverman, Laura C. Lazzeroni, Raquel E. Gur, Adam X. Maihofer, Ruben C. Gur, Michael F. Green, Caroline M. Nievergelt, Allen D. Radant, Monica E. Calkins, William S. Stone, Neal R. Swerdlow, Ming T. Tsuang, Keith H. Nuechterlein, and Robert Freedman
Subjects: Adult, Male, Potassium Channels, Endophenotypes, Genome-wide association study, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Social cognition, mental disorders, Genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, 2.1 Biological and endogenous factors, Medicine, Humans, Psychology, Cognitive Dysfunction, Aetiology, Episodic memory, Neuregulins, Other Medical and Health Sciences, business.industry, Human Genome, Neurosciences, Middle Aged, Genetic architecture, Brain Disorders, 030227 psychiatry, Psychiatry and Mental health, Mental Health, Good Health and Well Being, Endophenotype, Cohort, Schizophrenia, Female, Cognitive Sciences, business, Neurocognitive, 030217 neurology & neurosurgery, Imputation (genetics), Genome-Wide Association Study
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
Published: 2019

21. Depressive Symptoms Are Associated with Cognitive Function in the Elderly with Type 2 Diabetes

Author: Ramit Ravona-Springer, Derek LeRoith, Rachel Preiss, Ruth Zukran, Michal Schnaider Beeri, James Schmeidler, Elizabeth Guerrero-Berroa, Laili Soleimani, Anthony Heymann, Jeremy M. Silverman, and Mary Sano
Subjects: Male, 03 medical and health sciences, depressive symptoms, Cognition, 0302 clinical medicine, medicine, Humans, Dementia, Prospective Studies, Cognitive decline, Risk factor, Episodic memory, cognitive function, Depression (differential diagnoses), Aged, Aged, 80 and over, diabetes, 030214 geriatrics, Depression, Working memory, business.industry, General Neuroscience, Cognitive domains, General Medicine, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Geriatric Depression Scale, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Research Article, Clinical psychology
Abstract: Background: Type 2 diabetes (T2D) is a metabolic condition associated with poor clinical and cognitive outcomes including vascular disease, depressive symptoms, cognitive impairment, and dementia. In the general elderly population, depression has been consistently identified as a risk factor for cognitive impairment/decline. However, the association between depression and cognitive function in T2D has been understudied. Objective: We investigated the association between depression and cognitive function in a large sample of cognitively normal elderly with T2D. Methods: In this cross-sectional study, we examined 738 participants, aged 65–88 years old, enrolled in the Israel Diabetes and Cognitive Decline study. For each cognitive domain (Episodic Memory, Executive Function, Attention/Working Memory, Language/Semantic Categorization) and Overall Cognition, multiple linear regressions assessed its association with depression (score greater than 5 on the 15-item version of the Geriatric Depression Scale [GDS]), adjusting for age, sex, and education. Results: Depression (n = 66, 8.9%) was associated with worse performance on tasks of Executive Function (p = 0.004), Language/Semantic Categorization (p
Published: 2018

22. Age Modulates the Association of Caffeine Intake With Cognition and With Gray Matter in Elderly Diabetics

Author: Abigail Livny, Rebecca K. West, Anthony Heymann, Derek LeRoith, Rachel Preiss, Jeremy M. Silverman, Ramit Ravona-Springer, Danit R. Shahar, Ruth Zukran, and Michal Schnaider-Beeri
Subjects: Male, Aging, Physiology, Type 2 diabetes, 03 medical and health sciences, chemistry.chemical_compound, Cognition, 0302 clinical medicine, Caffeine, Diabetes mellitus, Humans, Medicine, 030212 general & internal medicine, Effects of sleep deprivation on cognitive performance, Gray Matter, Israel, Cognitive decline, Aged, business.industry, Working memory, Organ Size, medicine.disease, Magnetic Resonance Imaging, White Matter, Diabetes Mellitus, Type 2, chemistry, The Journal of Gerontology: Medical Sciences, Brain size, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND: The association between caffeine and cognitive performance has not been tested in older individuals with type 2 diabetes (T2D). Its association with brain volume in T2D has been tested only in animals. METHODS: We examined the association of caffeine with cognitive function and brain volume in a sample of elderly diabetics participating in the Israel Diabetes and Cognitive Decline Study (n = 638) and the moderating effect of age on this association. In a subsample (n = 185) with magnetic resonance imaging, we also examined these associations with gray and white matter volumes (GM/WM). RESULTS: Using linear regression adjusting for cognition-related covariates, we found that higher caffeine intake was associated with better function in overall cognition (p = .018), attention/working memory (p = .002), executive functioning (p = .047), and semantic categorization (p = .026). Interaction analyses of caffeine intake with age were significant for semantic categorization (p = .025), and approached significance for overall cognition (p = .066). This association was driven by the older group (above-median) for whom the association of caffeine intake with semantic categorization (p = .001), attention/working memory (p = .007), executive functioning (p = .005), and overall cognition (p = .002) were significant. In the magnetic resonance imaging subsample, there was an interaction (p = .034) of caffeine intake with age for GM volume; in the older group, higher caffeine intake was associated with greater GM volume (β = .198, p = .033). CONCLUSIONS: Caffeine intake may have a beneficial role in cognitive functioning of elderly adults with T2D, which may be moderated by age. Greater GM volume may be a mechanism underlying the association of higher caffeine intake with better cognitive function.
Published: 2018

23. Outcome age‐based prediction of successful cognitive aging by total cholesterol

Author: James Schmeidler and Jeremy M. Silverman
Subjects: Male, Time Factors, Statin, Epidemiology, medicine.drug_class, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Framingham Heart Study, Developmental Neuroscience, Risk Factors, Humans, Medicine, Dementia, Cognitive Dysfunction, Longitudinal Studies, 030212 general & internal medicine, Cognitive decline, Survival analysis, Aged, Aged, 80 and over, Cholesterol, Proportional hazards model, business.industry, Health Policy, Cognition, Prognosis, medicine.disease, Survival Analysis, Psychiatry and Mental health, chemistry, Cognitive Aging, Female, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Demography
Abstract: Introduction Some associations of high total cholesterol with dementia risk diminish as the outcome age—age at cognitive assessment—increases. Methods The Framingham Heart Study provided 1897 participants with intact cognition at entry. Cox regression analysis for incident marked cognitive decline included "time-dependent" coefficients, with associations between total cholesterol and covariates changing by outcome age. Decline within age categories of 75–84 and 85–94 years was also examined. Results Significant associations of rising total cholesterol linear slope, low entry age, low education, and statin nonuse with risk diminished significantly by outcome age. At 85–94 years, falling linear slope was significant. Discussion The protected survival model posits a minority subpopulation with protection against mortality and cognitive decline associated with total cholesterol risk factors. It predicts the observed diminished or reversed cholesterol associations with increasing age. Protection is particularly likely for successful cognitive aging—intact cognition at very old age—despite increased risk from cholesterol.
Published: 2018

24. The protected survivor model: Using resistant successful cognitive aging to identify protection in the very old

Author: Jeremy M. Silverman and James Schmeidler
Subjects: Gerontology, Cognitive aging, Aging, Population, Protective factor, Disease, Models, Psychological, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Humans, Cognitive Dysfunction, Longitudinal Studies, Survivors, 030212 general & internal medicine, Cognitive decline, Risk factor, education, Aged, Proportional Hazards Models, Aged, 80 and over, education.field_of_study, Proportional hazards model, Cognition, General Medicine, Middle Aged, Cardiovascular Diseases, Cognitive Aging, Psychology, 030217 neurology & neurosurgery
Abstract: For some cardiovascular risk factors, association with risk for cognitive impairment observed in early old age is reduced, or paradoxically even reversed, as age of outcome increases. Successful cognitive aging is intact cognition in the oldest-old; we define resistant successful cognitive aging as successful cognitive aging despite high risk. The protected survivor model posits that a minority of the general population has a protective factor that mitigates the negative effect of a risk factor on successful cognitive aging for the unprotected majority. As age increases, differential failure rates increase the proportion of survivors with protection. Among the unprotected, the proportion with low risk increases, but among those with protection, high risk and low risk do not differ. Due to differential mortality, half the survivors are eventually protected - a majority among those with high risk, and a minority among those with low risk. According to the protective survivor model, an example of Simpson's paradox, the association of the risk factor with survival does not change within an individual, but the association in the surviving population changes as its age increases. We created quantitative illustrations of a simplified protected survivor model applied to successful cognitive aging to explain how the usual association of a risk factor with cognitive decline is reversed in the very old. In the illustrations, probability of subsequent survival was higher for survivors with high risk (mostly protected) than low risk (mostly not protected), an example of Simpson's paradox. Resistance to disease despite the presence of risk factors is consistent with the presence of countervailing protection. Based on the protected survivor model, we hypothesize that studies seeking protective factors against cognitive decline will be more effective by limiting a successful cognitive aging sample to resistant successful cognitive aging - to contrast with a sample without successful cognitive aging.
Published: 2018

25. Hemoglobin A1c Variability Predicts Symptoms of Depression in Elderly Individuals With Type 2 Diabetes

Author: Anthony Heymann, Ruth Tzukran, Derek LeRoith, Rachel Preiss, Ramit Ravona-Springer, Mary Sano, Erin Moshier, Jeremy M. Silverman, Elizabeth Guerrero-Berroa, Laili Soleimani, Michal Schnaider Beeri, and James Schmeidler
Subjects: Advanced and Specialized Nursing, Research design, medicine.medical_specialty, Cross-sectional study, business.industry, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Physical therapy, Geriatric Depression Scale, 030212 general & internal medicine, Cognitive decline, business, Depression (differential diagnoses), Glycemic
Abstract: OBJECTIVE This study aimed to analyze the relationship of variability in hemoglobin A1c (HbA1c) over years with subsequent depressive symptoms. RESEARCH DESIGN AND METHODS Subjects (n = 837) were participants of the Israel Diabetes and Cognitive Decline (IDCD) study, which aimed to examine the relationship of characteristics of long-term type 2 diabetes with cognitive decline. All pertain to a diabetes registry established in 1998, which contains an average of 18 HbA1c measurements per subject. The results presented here are based on the IDCD baseline examination. Symptoms of depression were assessed using the 15-item version of the Geriatric Depression Scale (GDS). To quantify the association between variability in glycemic control (measured as the SD of HbA1c measurements [HbA1c-SD]) since 1998 with the number of depression symptoms at IDCD baseline, incidence rate ratios (IRRs) and corresponding 95% CIs were estimated via negative binomial regression modeling and used to account for the overdispersion in GDS scores. RESULTS Subjects’ ages averaged 72.74 years (SD 4.63 years), and the mean number of years in the diabetes registry was 8.7 (SD 2.64 years). The mean GDS score was 2.16 (SD 2.26); 10% of subjects had a GDS score ≥6, the cutoff for clinically significant depression. Mean HbA1c significantly correlated with HbA1c-SD (r = 0.6625; P < 0.0001). The SD, but not the mean, of HbA1c measurements was significantly associated with the number of subsequent depressive symptoms. For each additional 1% increase in HbA1c-SD, the number of depressive symptoms increased by a factor of 1.31 (IRR = 1.31 [95% CI 1.03–1.67]; P = 0.03). CONCLUSIONS Variability in glycemic control is associated with more depressive symptoms.
Published: 2017

26. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Author: Patricia T. Michie, Franziska Degenhardt, Brandon Wormley, Paola Giusti-Rodríguez, Mark J. Daly, Raquelle I. Mesholam-Gately, Ingrid Melle, Sibylle G. Schwab, Andrew McQuillin, Benjamin M. Neale, Joshua L. Roffman, Abraham Reichenberg, Pamela Sklar, Diana O. Perkins, Jennifer L. Moran, Donald W. Black, Per Hoffmann, A. Hofman, Hailiang Huang, John L. Waddington, Giulio Genovese, Aaron R. Wolen, Deborah L. Levy, David Curtis, Digby Quested, Carlos N. Pato, Nicholas John Craddock, Stephanie Williams, Kung Yee Liang, Zhouzhi Wang, Tracey L. Petryshen, Ann E. Pulver, Randy L. Buckner, Stephan Ripke, Roel A. Ophoff, Danielle Posthuma, Lili Milani, Jacques Mallet, Menachem Fromer, Christian R. Marshall, Jaana Suvisaari, Jana Strohmaier, Richard Bruggeman, Marcella Rietschel, Ayman H. Fanous, Andrew M. McIntosh, James T.R. Walters, Dimitris Dikeos, Panos Roussos, Veikko Salomaa, Aiden Corvin, Carin J. Meijer, Tiina Paunio, Assen Jablensky, Sarah E. Bergen, Nancy G. Buccola, Annelie Nordin, Wolfgang Maier, Srdjan Djurovic, Naomi R. Wray, Aniket Shetty, Joel Eriksson, Dan Rujescu, Jouko Lönnqvist, Brian Kelly, Wenting Wu, Alexander Richards, Frans Henskens, Rich Belliveau, Bryan J. Mowry, Elodie Drapeau, Andreas J. Forstner, Silviu Alin Bacanu, Jubao Duan, Tõnu Esko, Bernard Lerer, Carmel M. Loughland, Olli Pietiläinen, Michael Conlon O'Donovan, Shaun M. Purcell, Michael Gill, Thomas G. Schulze, Douglas S. Greer, Stephen W. Scherer, Eli A. Stahl, Markus M. Nöthen, Guiqing Cai, William M. Brandler, Kristin K. Nicodemus, Dominique Campion, David A. Collier, Farooq Amin, Joel N. Hirschhorn, Robin M. Murray, Timothy G. Dinan, Mark Reimers, Murray J. Cairns, Rodney J. Scott, Aarno Palotie, Robert Freedman, Nelson B. Freimer, Joshua R. Atkins, Gary Donohoe, Ann Olincy, Jonathan Sebat, Colm McDonald, Srinivas Thirumalai, John Powell, Jo Knight, Vahram Haroutunian, Dieter B. Wildenauer, Tim B. Bigdeli, Lieuwe de Haan, Peter Eichhammer, James J. Crowley, Lynn E. DeLisi, Ulrich Schall, Rolf Adolfsson, Marcelo Bertalan, Thomas Hansen, Eric Strengman, Michael Davidson, Dheeraj Malhotra, Manuel Mattheisen, Jeffrey A. Lieberman, Benedicto Crespo-Facorro, Stephanie Godard, Edward M. Scolnick, Jonathan Pimm, Bertram Müller-Myhsok, Qingqin Li, Michele T. Pato, Wiepke Cahn, Christos Pantelis, Ingrid Agartz, Brendan Bulik-Sullivan, Madhusudan Gujral, Martilias S. Farrell, Brady J. Maher, Laurent Essioux, Karin V Fuentes Fajarado, Andres Metspalu, Stephanie H. Witt, Patrick F. Sullivan, Mark Weiser, Younes Mokrab, Kai How Farh, Line Olsen, Dermot Walsh, Peter Holmans, Hugh Gurling, Joseph I. Friedman, Andrew Pocklington, Daniel P. Howrigan, Lude Franke, Tune H. Pers, Larry J. Seidman, Pablo V. Gejman, Dalila Pinto, Michael John Owen, Inez Myin-Germeys, Steven A. McCarroll, Wei Cheng, Jackie Goldstein, C. Robert Cloninger, Elliot S. Gershon, Deborah A. Nertney, Thomas Werge, Noa Carrera, Kieran C. Murphy, Rita M. Cantor, Ariel Darvasi, Mark Hansen, Annette M. Hartmann, Ole A. Andreassen, Bradley T. Webb, Henrik B. Rasmussen, David Cohen, Elvira Bramon, Erik G. Jönsson, Vaughan J. Carr, Pui Y. Lee, Masashi Ikeda, Daniele Merico, Danny Antaki, Brien P. Riley, Stefan Herms, Igor Nenadic, Bettina Konte, Kimberley D. Chambert, Jurgen Del Favero, George Kirov, Matthew C. Keller, Jacob Gratten, Douglas F. Levinson, Luba Kalaydjieva, Bhooma Thiruvahindrapuram, Alan R. Sanders, Sang-Yun Oh, Alkes L. Price, Vihra Milanova, Juha Veijola, Erik Söderman, Dragan M. Svrakic, David H. Kavanagh, Patrik K. E. Magnusson, Douglas Blackwood, Nakao Iwata, Jim van Os, Jeremy M. Silverman, Elena Parkhomenko, Kenneth L. Davis, Jing Qin Wu, Eadbhard O'Callaghan, Chris C. A. Spencer, Juha Karjalainen, Anna K. Kähler, Clement C. Zai, Nigel Williams, Joseph D. Buxbaum, Jin P. Szatkiewicz, Laura Nisenbaum, Sang Hong Lee, Yunjung Kim, Colm O'Dushlaine, René S. Kahn, Morten Mattingsdal, Inge Joa, Marian L. Hamshere, Frank Dudbridge, Ina Giegling, Sandra Meier, Derek W. Morris, Robert W. McCarley, Douglas M. Ruderfer, Paul Cormican, Lyudmila Georgieva, Sven Cichon, Josef Frank, Jianxin Shi, George N. Papadimitriou, Kenneth S. Kendler, Margot Albus, Enrico Domenici, Claudine Laurent, Francis A. O'Neill, Adam Savitz, Jordan W. Smoller, James L. Kennedy, Peter M. Visscher, Valentina Escott-Price, Christina M. Hultman, T. Scott Stroup, Elizabeth Bevilacqua, James A. Knowles, William Byerley, Paul A. Tooney, Madeline Alexander, Stanley V. Catts, David St Clair, Sophie E. Legge, Gerald Nestadt, Michelle S. Maile, Perceptual and Cognitive Neuroscience (PCN), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Stem Cell Aging Leukemia and Lymphoma (SALL), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Psychiatrie (3), Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, Other departments, Marshall, Christian R, Howrigan, Daniel P, Merico, Daniele, Thiruvahindrapuram, Bhooma, Lee, S Hong, Sebat, Jonathan, Psychosis Endophenotypes International Consortium, CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium, CNV, Schizophrenia Working Grp, Psychosis Endophenotypes, Rehabilitation Medicine, and Child and Adolescent Psychiatry / Psychology
Subjects: 0301 basic medicine, Male, 16P11.2, Duplication, Autism, Rearrangement, Genome-wide association study, Copy number variant, Gene, Medical and Health Sciences, 0302 clinical medicine, DUPLICATIONS, Risk Factors, Gene duplication, Genotype, Disorder, Copy-number variation, Genetics, Genetics & Heredity, RISK, copy number variation, REARRANGEMENTS, Biological Sciences, 16p11.2, 3. Good health, Phenotype, Female, Risk, CNVS, Genetic Markers, genetic etiology, CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium, DNA Copy Number Variations, DISORDERS, CNV, Non-allelic homologous recombination, PHENOTYPES, Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, genomics, Journal Article, Humans, Comparative Study, Genetic Predisposition to Disease, AUTISM, Psychosis Endophenotypes International Consortium, MUTATIONS, Case-control study, Odds ratio, R1, GENE, 030104 developmental biology, genetics research, Genetic marker, Genetic Loci, Case-Control Studies, Mutation, Schizophrenia, Human medicine, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination. Refereed/Peer-reviewed
Published: 2017

27. Recruitment of Older Veterans with Diabetes Risk for Alzheimer's Disease for a Randomized Clinical Trial of Computerized Cognitive Training

Author: Jeremy M. Silverman, Neil B. Alexander, Michal Schnaider Beeri, James Schmeidler, Martha Karran, Elizabeth Guerrero-Berroa, Pearl G. Lee, Mary Sano, Rebecca K. West, and Martina Nabozny
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Diabetes risk, Population, Psychological intervention, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Informed consent, Alzheimer Disease, Risk Factors, medicine, Dementia, Humans, Cognitive Dysfunction, education, Aged, Veterans, Aged, 80 and over, education.field_of_study, Cognitive Behavioral Therapy, business.industry, General Neuroscience, Patient Selection, Cognition, General Medicine, Middle Aged, medicine.disease, Mental Status and Dementia Tests, Cognitive training, United States, Psychiatry and Mental health, Clinical Psychology, United States Department of Veterans Affairs, 030104 developmental biology, Diabetes Mellitus, Type 2, Family medicine, Therapy, Computer-Assisted, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: Background Type 2 diabetes mellitus (T2DM) is prevalent in the general United States population, and in the veteran population. T2DM has consistently been linked to increased risk for cognitive impairment, dementia, and Alzheimer's disease. Computerized cognitive training (CCT) is practical and inexpensive cognitive interventions that is an alternative to medication. Objective To report the recruitment methods and challenges to date in an ongoing two-site randomized controlled trial (RCT) of CCT on cognitive function and T2DM management in an older non-demented veteran population. Methods Veterans are recruited primarily by targeted mailings or by direct contact at clinics and presentations. Results From 1,459 original contacts, 437 expressed initial interest, 111 provided informed consent, and 97 completed baseline assessments. Participants from the two VA Medical Centers differed in demographics and baseline characteristics. Comparing recruitment methods, the proportion of individuals contacted who were ultimately consented was significantly less from mailings (5%) than other sources (20%), primarily face- to-face clinic visits (χ2 (1) = 38.331, p Conclusions Mailings are cost-effective, but direct contact improved recruitment. Not using or lacking access to computers and ineligibility were major reasons for non-participation. Within-site comparisons of demographically diverse sites can address confounding of demographic and other site differences.
Published: 2019

28. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author: Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. Docherty, Jim van Os, Nese Direk, Lina Martinsson, Maria Arranz, Christel M. Middeldorp, Stefan Kloiber, Sintia Iole Belangero, Eske M. Derks, Ingrid Melle, Erlend Bøen, Jan Haavik, Federica Piras, Unna N. Danner, Anil K. Malhotra, Gerome Breen, Stephen V. Faraone, Amanda B Zheutlin, Timothy Poterba, Stephan Ruhrmann, Inge Joa, Ulrik Fredrik Malt, Sarah E. Bergen, Federica Tozzi, Lauren A. Weiss, Hana Papezova, Dominic Holland, Elliot S. Gershon, Jaakko Kaprio, Merete Nordentoft, Scott D. Gordon, Christopher Pittenger, Keun-Ah Cheon, Jennifer Jordan, Philip Gorwood, Myrna M. Weissman, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Isobel Heyman, Eun-Young Shin, Christie L. Burton, Katherine Gordon-Smith, Sietske G. Helder, Peter Nagy, Till F. M. Andlauer, Yunpeng Wang, Young Key Kim, Kate Langley, Søren Dalsgaard, Richard Delorme, Torbjørn Elvsåshagen, Bennett L. Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. McGough, Michael Gill, Christel Depienne, Roland Burghardt, Antonio Julià, Anders M. Dale, Sven Sandin, Katharina Domschke, Maria Grigoroiu-Serbanescu, Susana Jiménez-Murcia, Marianne Giørtz Pedersen, Zsanett Tarnok, Gisli Baldursson, Michele T. Pato, David M. Hougaard, Thorgeir E. Thorgeirsson, Katharina Bey, Kerstin J. Plessen, Margaret A. Richter, Ole A. Andreassen, Claudine Laurent-Levinson, Leonid Padyukov, Jacques Mallet, Daniela Degortes, John R. Kelsoe, Robert D. Levitan, Andreas Reif, Chaim Huyser, Derek W. Morris, Sina Wanderer, William Byerley, Edna Grünblatt, E.J.C. de Geus, Hyejung Won, Josephine Elia, Rudolf Uher, Jay A. Tischfield, Andreas Karwautz, Gustavo Turecki, Pieter J. Hoekstra, Dorret I. Boomsma, Jacob Rosenthal, Daniele Cusi, Michael C. Neale, Sara Mostafavi, Gwyneth Zai, F. Anthony O'Neill, Gary Donohoe, Karola Rehnström, Harry Brandt, Helena Gaspar, Francis J. McMahon, H-Erich Wichmann, Andrew W. Bergen, Giovanni Coppola, Lea K. Davis, Lenka Slachtova, Olav B. Smeland, Erin C. Dunn, Nicholas G. Martin, Allan L. Naarden, Jo Knight, Cristina Sánchez-Mora, Masashi Ikeda, Lorraine Southam, Sandro Sorbi, Barbara Franke, Martin Schalling, Russell Schachar, Yen-Chen Anne Feng, Kirsten R. Müller-Vahl, André Scherag, Zhaozhong Zhu, Eric A. Storch, Páll Magnússon, David Cohen, Olafur O Gudmundsson, Harvey S. Singer, Brian Kelly, Jonas Bybjerg-Grauholm, Blanca Garcia-Delgar, Thomas Hansen, Carmel M. Loughland, Christine Lochner, Stacy Steinberg, Martin Woods, Jorge A. Quiroz, Raquel Rabionet, Alden Y. Huang, Janice M. Fullerton, María Soler Artigas, Hans J. Grabe, Philip Asherson, Margit Burmeister, Alicia R. Martin, Martin A. Kennedy, Janet Treasure, Anders D. Børglum, Eva C. Schulte, Andreas Hartmann, Frans Henskens, Youl-Ri Kim, Jens Treutlein, Joanna Hauser, Manfred M. Fichter, Damiaan Denys, Ann E. Pulver, Kelly L. Klump, Paul Sandor, Michael Wagner, Philippe Courtet, Sandra Van der Auwera, Susanne Lucae, Eystein Stordal, Michel G. Nivard, Maurizio Clementi, Astrid Morer, Philip B. Mitchell, Huda Akil, Edwin H. Cook, Jennifer L. Moran, Donald W. Black, Jeremiah M. Scharf, Jana Strohmaier, Colm McDonald, Meg M.-J. Wang, Richard M. Myers, Stephanie Godard, Pablo V. Gejman, Athanasios Maras, Marcella Rietschel, Nancy G. Buccola, Konstantinos Hatzikotoulas, Dalila Pinto, Jouke-Jan Hottenga, Kari Stefansson, James S. Sutcliffe, Andres Metspalu, Amaia Hervás, Joel Gelernter, Wolfgang Herzog, Paula Rovira, Gunnar Morken, Tara Murphy, Mark Weiser, Vincent Millischer, Frank Dudbridge, Dan Rujescu, Vladimir Bencko, Valdo Ricca, Kimberly Chambert, Guy A. Rouleau, James J. Crowley, Thomas G. Schulze, Toni-Kim Clarke, Triinu Peters, Gudrun Wagner, Daniel A. Geller, Henry R. Kranzler, G. Bragi Walters, Vera Golimbet, Clement C. Zai, Nigel Williams, Andreas Birgegård, Joseph D. Buxbaum, Elliot M. Tucker-Drob, Jerome C. Foo, Tracey L. Petryshen, Daniel P. Howrigan, Hunna J. Watson, Franziska Degenhardt, Peter R. Schofield, Jesper Buchhave Poulsen, Stefan Herms, Johannes Hebebrand, Mario Maj, George Kirov, Fabrizio Piras, Sara McDevitt, James T. McCracken, Carol A. Mathews, Michael John Owen, Peter Falkai, Donald L. Gilbert, Enda M. Byrne, Fernando Fernández-Aranda, Csaba Barta, Stéphane Jamain, Jubao Duan, Dongmei Yu, Danielle C. Cath, Ole Mors, Sigrun Hope, Laramie E. Duncan, Alan R. Sanders, Sang-Yun Oh, Carsten Bøcker Pedersen, Henning Tiemeier, Roseann E. Peterson, Raymond K. Walters, Margarita C T Slof-Op 't Landt, Madeline Alexander, Stephanie Le Hellard, Ina Giegling, Annemarie A. van Elburg, Steven P. Hamilton, Vesna Boraska Perica, Thomas V. Fernandez, Danielle M. Dick, Francesco Bettella, Roel A. Ophoff, Grant W. Montgomery, Gerald Nestadt, Nakao Iwata, Jessica H. Baker, Walter H. Kaye, Jeremy M. Silverman, Mark J. Daly, Robert A. King, Sarah E. Medland, Anastasios Konstantinidis, Robert D. Oades, Samuel H. Zinner, Steven Crawford, Daniel H. Geschwind, Patrick W. L. Leung, Martin Alda, Marie Navratilova, Pak C. Sham, Paul A. Tooney, Tian Ge, Veit Roessner, Martin Preisig, Thomas Werge, Eli A. Stahl, David A. Collier, Stephanie H. Witt, Dermot Walsh, Miquel Casas, Anna Keski-Rahkonen, Jane H. Christensen, Silvia De Rubeis, Giorgio Pistis, Sven Cichon, Bruno Etain, Dominique Campion, O. Joseph Bienvenu, Christian Dina, Manolis Kogevinas, Thomas Espeseth, Benjamin M. Neale, Ditte Demontis, Klaus-Peter Lesch, Marina Mitjans, Tiffany A. Greenwood, Marcos Madruga-Garrido, Sibylle G. Schwab, Oedegaard Ketil Joachim, Hreinn Stefansson, Sara A. Paciga, Monica Forzan, Dieter B. Wildenauer, Lena Backlund, A. Jeremy Willsey, Carlos N. Pato, Nicholas John Craddock, Inge A. Meijer, Sandra K. Loo, Filip Rybakowski, Tracey D. Wade, Scott J. Crow, Bernard Lerer, Valsamma Eapen, Esben Agerbo, Andrew M. McIntosh, Luis Augusto Rohde, Susan L. McElroy, Stephan Zipfel, Peter P. Zandi, Cathryn M. Lewis, Lars Klareskog, Martin Begemann, Phil Lee, Richard Anney, Mark A. Bellgrove, Lisa Jones, Andreas J. Forstner, Agnieszka Słopień, Hilary Coon, Dong Li, Alessandro Serretti, Carsten Horn, Christos Pantelis, Ryan L. Collins, David M. Howard, Lucía Colodro-Conde, Pippa A. Thomson, Martin Hautzinger, Alysa E. Doyle, Julie Hagstrøm, Oliver S. P. Davis, Karen S. Mitchell, Jordan W. Smoller, Michael Strober, John I. Nurnberger, Andrea G. Ludolph, Monika Budde, Anna Maaser, Lambertus Klei, Aribert Rothenberger, Yulia Worbe, Fabian Streit, James L. Kennedy, Barbara E. Stranger, Ashley Dumont, Jianxin Shi, Dale R. Nyholt, Craig Johnson, Jonna Kuntsi, Yun-Joo Koh, Loes M. Olde Loohuis, Robert B. Freedman, Anke Hinney, Susanne Walitza, Enrico Domenici, Margarita Rivera, Sodahm Kook, Erica Greenberg, Tetyana Zayats, Josef Frank, Gary A. Heiman, Andrew McQuillin, Abraham Reichenberg, Piotr M. 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P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.
Subjects: Netherlands Twin Register (NTR), cross-disorder genetics, Medizin, Genome-wide association study, Tourette syndrome, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, Psychiatric genetics, 0302 clinical medicine, Pleiotropy, functional genomic, WIDE ASSOCIATION, cross-disorder genetic, 0303 health sciences, Mental Disorders, Genetic Pleiotropy, HUMAN BRAIN, INSIGHTS, Autism spectrum disorder, Schizophrenia, DISEASES, GENETIC CORRELATIONS, medicine.medical_specialty, Neurogenesis, Quantitative Trait Loci, BF, Biology, GENOTYPE IMPUTATION, Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics, Article, General Biochemistry, Genetics and Molecular Biology, psychiatric disorder, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, TRANSCRIPTOME, Psychiatry, 030304 developmental biology, Gwas, Psychiatric Genetics, Cross-disorder Genetics, Functional Genomics, Gene Expression, Genetic Architecture, Genetic Correlation, Neurodevelopment, Psychiatric Disorders, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, MUTATIONS, medicine.disease, Genetic architecture, DEMETHYLASE, RC0321, 1182 Biochemistry, cell and molecular biology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
Published: 2019

29. Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study

Author: Ruben C. Gur, Raquel E. Gur, Jane B. Shofer, Michael F. Green, Joyce Sprock, Steven P. Millard, Robert Freedman, Neal R. Swerdlow, Debby W. Tsuang, Ming T. Tsuang, Tiffany A. Greenwood, Laura C. Lazzeroni, Larry J. Seidman, Keith H. Nuechterlein, Ann Olincy, Monica E. Calkins, Larry J. Siever, Catherine A. Sugar, Allen D. Radant, William S. Stone, Bruce I. Turetsky, Gregory A. Light, David L. Braff, Jeremy M. Silverman, and Kristin S. Cadenhead
Subjects: Adult, Male, Multivariate statistics, Adolescent, Endophenotypes, Schizophrenia (object-oriented programming), Logistic regression, Neuropsychological Tests, Medical and Health Sciences, Article, Statistical power, Developmental psychology, Young Adult, 03 medical and health sciences, Sensitivity, 0302 clinical medicine, Clinical Research, Genetics, Humans, Family, Accuracy, Biological Psychiatry, Aged, Psychiatry, California Verbal Learning Test, Psychology and Cognitive Sciences, Middle Aged, Missing data, ROC curve, Brain Disorders, 030227 psychiatry, Endophenotype, Psychiatry and Mental health, Mental Health, Logistic Models, ROC Curve, Wide Range Achievement Test, Multivariate Analysis, Multiple imputation, Specificity, Schizophrenia, Female, Schizophrenic Psychology, Psychology, 030217 neurology & neurosurgery, Random forest, Clinical psychology
Abstract: Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving the statistical power of locating those genetic regions associated with schizophrenia that may be the easiest to identify initially.
Published: 2016

30. Waist circumference is correlated with poorer cognition in elderly type 2 diabetes women

Author: Michal Schnaider-Beeri, Elizabeth Guerrero-Berroa, Keren Koifman, Ramit Ravona-Springer, Jeremy M. Silverman, Rebecca K. West, Xiaowei Song, Anthony Heymann, James Schmeidler, Hadas Hoffman, Derek LeRoith, Rachel Preiss, Ryan C.N. D'Arcy, and Mary Sano
Subjects: Male, Gerontology, Aging, Waist, Epidemiology, Type 2 diabetes, 030204 cardiovascular system & hematology, Article, Developmental psychology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Risk Factors, medicine, Humans, Dementia, Effects of sleep deprivation on cognitive performance, Episodic memory, Aged, 80 and over, Sex Characteristics, Working memory, Health Policy, nutritional and metabolic diseases, Cognition, Circumference, medicine.disease, Psychiatry and Mental health, Diabetes Mellitus, Type 2, Female, Neurology (clinical), Waist Circumference, Geriatrics and Gerontology, Cognition Disorders, Psychology, 030217 neurology & neurosurgery
Abstract: Introduction Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood. Methods We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D). Results In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance ( P P = .026), and overall cognition ( P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes-related, APOE e4, and inflammatory potential confounders. Attention/working memory ( P = .532) and episodic memory ( P = .144) were not associated with waist circumference. These correlations were not found in men. Discussion These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia.
Published: 2016

31. Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History

Author: Michael F. Green, Bruce I. Turetsky, Debby W. Tsuang, Larry J. Siever, Laura C. Lazzeroni, Keith H. Nuechterlein, Larry J. Seidman, Ann Olincy, Robert Freedman, Tiffany A. Greenwood, Neal R. Swerdlow, Ming T. Tsuang, Catherine A. Sugar, Monica E. Calkins, Allen D. Radant, William S. Stone, Ruben C. Gur, Jeremy M. Silverman, Gregory A. Light, David L. Braff, and Raquel E. Gur
Subjects: Parents, Adult, Male, Proband, medicine.medical_specialty, Adolescent, Endophenotypes, Severity of Illness Index, Medical and Health Sciences, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Genetics, medicine, Humans, Family, Family history, Psychiatry, Evoked Potentials, Nuclear family, Prepulse inhibition, Aged, Prepulse Inhibition, Siblings, Human Genome, Psychology and Cognitive Sciences, Neurosciences, Brain, Electroencephalography, Middle Aged, Heritability, medicine.disease, Brain Disorders, 030227 psychiatry, Psychiatry and Mental health, Mental Health, Schizophrenia, Endophenotype, Schizophrenic Psychology, Female, Psychology, Neurocognitive, 030217 neurology & neurosurgery, Clinical psychology
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.
Published: 2016

32. Deficient prepulse inhibition in schizophrenia in a multi-site cohort: Internal replication and extension

Author: Tiffany A. Greenwood, Bruce I. Turetsky, Michael L. Thomas, Larry J. Seidman, Catherine A. Sugar, Joyce Sprock, Ruben C. Gur, Raquel E. Gur, Michael F. Green, Jeremy M. Silverman, Monica E. Calkins, Larry J. Siever, Gregory A. Light, Debby W. Tsuang, Laura C. Lazzeroni, David L. Braff, Neal R. Swerdlow, Ming T. Tsuang, Keith H. Nuechterlein, Allen D. Radant, and William S. Stone
Subjects: Oncology, Male, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, 2.1 Biological and endogenous factors, Aetiology, Prepulse inhibition, Psychiatry, Prepulse Inhibition, Multi site, Startle, Middle Aged, Psychiatry and Mental health, Endophenotype, Mental Health, Schizophrenia, Cohort, Female, Analysis of variance, Psychology, Antipsychotic Agents, Adult, medicine.medical_specialty, Adolescent, Endophenotypes, Replication, Article, 03 medical and health sciences, Young Adult, Clinical Research, Internal medicine, Replication (statistics), medicine, Neurologic, Humans, Gait Disorders, Biological Psychiatry, Gait Disorders, Neurologic, Psychiatric Status Rating Scales, Analysis of Variance, Psychology and Cognitive Sciences, Neural Inhibition, medicine.disease, 030227 psychiatry, Brain Disorders, Acoustic Stimulation, Hearing acuity, 030217 neurology & neurosurgery
Abstract: BACKGROUND: The 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. METHODS: PPI 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. RESULTS: ANOVA of all W(1+2) subjects revealed robust PPI deficits in patients across “waves” (p
Published: 2018

33. P2‐607: DEPRESSIVE SYMPTOMS PREDICT COGNITIVE DECLINE IN OLDER ADULTS

Author: Michal Schnaider Beeri, James Schmeidler, Rebecca K. West, Jeremy M. Silverman, Mary Sano, Joshua Arneson, Vahram Haroutunian, and Elizabeth Guerrero-Berroa
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business, Depressive symptoms, Clinical psychology
Published: 2018

34. Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

Author: Guiyan Ni, Gerhard Moser, Naomi R. Wray, S. Hong Lee, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Juliá, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsda, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olinc, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papio, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinenl, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Jordan W. Smoller, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stah, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Kari Stefansson, Peter M. Visscher, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarrol, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietsche, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O’Donovan, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, Ni, Guiyan, Moser, Gerhard, Wray, Naomi R, Lee, S Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Clinicum, Department of Psychiatry, and HUS Psychiatry
Subjects: 0301 basic medicine, Linkage disequilibrium, Schizophrenia/genetics, INFORMATION, Restricted maximum likelihood, Inheritance Patterns, linkage disequilibrium score regression, Bioinformatics, Medical and Health Sciences, 3124 Neurology and psychiatry, Linkage Disequilibrium, biasedness, 0302 clinical medicine, Statistics, Databases, Genetic, WIDE ASSOCIATION, Genetics(clinical), PARTITIONING HERITABILITY, Genetics (clinical), Genetics & Heredity, education.field_of_study, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Likelihood Functions, Genome, Body Height/genetics, accuracy, Regression analysis, Single Nucleotide, Biological Sciences, Polymorphism, Single Nucleotide/genetics, genetic correlation, Regression, STATISTICS, genomic restricted maximum likelihood, Mental Health, Phenotype, Regression Analysis, COMPLEX HUMAN TRAITS, Single Nucleotide/genetics, Human, Adult, SUSCEPTIBILITY LOCI, Genotype, SNP heritability, body mass index, genome-wide SNPs, height, schizophrenia, Population, Haplotypes/genetics, Biology, Genetic correlation, Polymorphism, Single Nucleotide, 03 medical and health sciences, Databases, Genetic, ddc:570, Report, Genetics, Humans, Linkage Disequilibrium/genetics, Computer Simulation, Polymorphism, education, linkage disequilibrium score regression (LDSC), Genome, Human, Human Genome, genetic architecture, Genetic architecture, Body Height, Brain Disorders, Inheritance Patterns/genetics, BODY-MASS INDEX, 030104 developmental biology, Haplotypes, Sample size determination, Schizophrenia, 3111 Biomedicine, HUMAN HEIGHT, 030217 neurology & neurosurgery
Abstract: J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen. Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.
Published: 2017

35. Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes

Author: James Schmeidler, Derek LeRoith, Elizabeth Guerrero-Berroa, Michal Schnaider-Beeri, Rachel Preiss, Andrew P. Levy, Keren Koifmann, Hadas Hoffman, Ramit Ravona-Springer, Jeremy M. Silverman, Lior Greenbaum, Mary Sano, and Anthony Heymann
Subjects: Gerontology, biology, business.industry, Working memory, Haptoglobin, 030209 endocrinology & metabolism, Cognition, Type 2 diabetes, medicine.disease, Ashkenazi jews, Genotype frequency, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, biology.protein, Medicine, Geriatrics and Gerontology, Cognitive decline, business, Episodic memory, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Objective The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. Methods This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. Results Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. Conclusions Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African–Americans and Hispanics. Copyright © 2015 John Wiley & Sons, Ltd.
Published: 2015

36. 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)

Author: Allen D. Radant, Keith H. Nuechterlein, William S. Stone, Monica E. Calkins, Robert Freedman, Neal R. Swerdlow, David L. Braff, Larry J. Siever, Ming T. Tsuang, Bruce I. Turetsky, Raquelle I. Mesholam-Gately, Raquel E. Gur, Catherine A. Sugar, Gregory A. Light, Joyce Sprock, Larry J. Seidman, Ruben C. Gur, Michael F. Green, Jeremy M. Silverman, Tiffany A. Greenwood, Debby W. Tsuang, Laura C. Lazzeroni, and Ann Olincy
Subjects: Male, Neuropsychological Tests, Medical and Health Sciences, California, Cohort Studies, California Verbal Learning Test, Psychology, 2.1 Biological and endogenous factors, Aetiology, Psychiatry, Analysis of covariance, Genetics, Verbal Learning, Middle Aged, Serious Mental Illness, Endophenotype, Psychiatry and Mental health, Memory, Short-Term, Mental Health, Cohort effect, Schizophrenia, Speech Perception, Schizophrenic Psychology, Female, Cohort study, Adult, Adolescent, Endophenotypes, Verbal learning, behavioral disciplines and activities, Article, Young Adult, Memory, Clinical Research, mental disorders, medicine, Humans, Family, Biological Psychiatry, Aged, Recall, Psychology and Cognitive Sciences, fungi, Neurosciences, Recognition, Psychology, medicine.disease, Brain Disorders, Recognition, Short-Term, Case-Control Studies, Mental Recall, human activities
Abstract: © 2014. 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.
Published: 2015

37. Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes

Author: Derek LeRoith, Rachel Preiss, Anthony Heymann, Jeremy M. Silverman, Ramit Ravona-Springer, Michal Schnaider Beeri, James Schmeidler, Jimmy Akrivos, Hadas Hoffman, and Keren Koifman
Subjects: medicine.medical_specialty, biology, C-reactive protein, Cognition, Type 2 diabetes, medicine.disease, Executive functions, Developmental psychology, Psychiatry and Mental health, chemistry.chemical_compound, chemistry, Internal medicine, Diabetes mellitus, medicine, biology.protein, Glycated hemoglobin, Geriatrics and Gerontology, Cognitive decline, Psychology, Glycemic
Abstract: Objective Glycated hemoglobin (HbA1c) and C-reactive protein (CRP) have been associated with cognitive impairment independently. However, it is unclear if their combination exacerbates poor cognitive function. We assessed whether long-term glycemic level and glycemic variability modulate the association of systemic inflammation with cognitive function, in a sample of cognitively normal older people with type 2 diabetes. Methods A retrospective cohort study of 777 randomly selected participants from ~11,000 patients in the Maccabi Healthcare Services Diabetes Registry, as part of the Israel Diabetes and Cognitive Decline study. Subjects averaged 18 (±9.4) HbA1c measures in the Maccabi Healthcare Services Registry, which were used to calculate long-term glycemic level (HbA1c-mean) and glycemic variability (HbA1c-standard deviation (SD)). Linear regression models assessed the interactions of CRP, a marker of systemic inflammation, with HbA1c-mean and HbA1c-SD on subjects' performance in tests of Memory, Executive Functions, Attention, and Semantic Categorization. Results Quadratic interactions of CRP with HbA1c-SD approached significance for executive functions and overall cognition. However, after Bonferroni adjustment, none of the interactions of CRP with HbA1c were statistically significant. In partial correlations according to HbA1c-SD tertiles, CRP was weakly correlated in the middle tertile with decreased performance in the domains of semantic categorization (r = −0.166, p = 0.011), executive functions (r = −0.136, p = 0.038), and overall cognition (r = −0.157, p = 0.016). Conclusions Glycated hemoglobin does not substantially modulate the association of CRP with cognition in a sample of cognitively normal, community dwelling older people with relatively well-managed type 2 diabetes. Copyright © 2015 John Wiley & Sons, Ltd.
Published: 2015

38. Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

Author: Bjarni J. Vilhjálmsson, Jian Yang, Hilary K. Finucane, Alexander Gusev, Sara Lindström, Stephan Ripke, Giulio Genovese, Po-Ru Loh, Gaurav Bhatia, Ron Do, Tristan Hayeck, Hong-Hee Won, Sekar Kathiresan, Michele Pato, Carlos Pato, Rulla Tamimi, Eli Stahl, Noah Zaitlen, Bogdan Pasaniuc, Gillian Belbin, Eimear E. Kenny, Mikkel H. Schierup, Philip De Jager, Nikolaos A. Patsopoulos, Steve McCarroll, Mark Daly, Shaun Purcell, Daniel Chasman, Benjamin Neale, Michael Goddard, Peter M. Visscher, Peter Kraft, Nick Patterson, Alkes L. Price, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Lynn E. DeLisi, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Lyudmila Georgieva, Elliot S. Gershon, Ina Giegling, Paola Giusti-Rodrguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Jakob Grove, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julia, Rene S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, Brian J. Kelly, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kahler, Claudine Laurent, Jimmy Lee Chee Keong, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lnnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Preben B. Mortensen, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Mller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietilinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Jordan W. Smoller, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Sderman, Srinivas Thirumalai, Draga Toncheva, Paul A. Tooney, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Jing Qin Wu, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tonu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jonsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Bryan J. Mowry, Markus M. Nthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St. Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O’Donovan, David J. Hunter, Muriel Adank, Habibul Ahsan, Kristiina Aittomäki, Laura Baglietto, Sonja Berndt, Carl Blomquist, Federico Canzian, Jenny Chang-Claude, Stephen J. Chanock, Laura Crisponi, Kamila Czene, Norbert Dahmen, Isabel dos Santos Silva, Douglas Easton, A. Heather Eliassen, Jonine Figueroa, Olivia Fletcher, Montserrat Garcia-Closas, Mia M. Gaudet, Lorna Gibson, Christopher A. Haiman, Per Hall, Aditi Hazra, Rebecca Hein, Brian E. Henderson, Albert Hofman, John L. Hopper, Astrid Irwanto, Mattias Johansson, Rudolf Kaaks, Muhammad G. Kibriya, Peter Lichtner, Eiliv Lund, Enes Makalic, Alfons Meindl, Hanne Meijers-Heijboer, Bertram Müller-Myhsok, Taru A. Muranen, Heli Nevanlinna, Petra H. Peeters, Julian Peto, Ross L. Prentice, Nazneen Rahman, María José Sánchez, Daniel F. Schmidt, Rita K. Schmutzler, Melissa C. Southey, Ruth Travis, Clare Turnbull, Andre G. Uitterlinden, Rob B. van der Luijt, Quinten Waisfisz, Zhaoming Wang, Alice S. Whittemore, Rose Yang, Wei Zheng, ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Grove, Jakob, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Vilhjalmsson, Bjarni J, Yang, Jian, Finucane, Hilary K, Gusev, Alexander, Lee, SH, Price, Alkes L, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Study, Psychosis Endophenotype International Consortium, Wellcome Trust Case Control Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Human genetics, NCA - Brain mechanisms in health and disease, CCA - Oncogenesis, CCA - Quality of life, CCA - Cancer biology and immunology, Psychiatry, Department of Technology and Operations Management, Department of Organisation and Personnel Management, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Cell biology, and Internal Medicine
Subjects: Multifactorial Inheritance, Linkage disequilibrium, Complex disease, heritability, Bioinformatics, Medical and Health Sciences, Linkage Disequilibrium, 0302 clinical medicine, Theoretical, External reference, Models, Statistics, GWAS, Genetics(clinical), Genetics (clinical), Mathematics, Genetics & Heredity, Schizophrenia Working Group of the Psychiatric Genomics Consortium, 0303 health sciences, Single Nucleotide, Biological Sciences, Serious Mental Illness, Prognosis, Thresholding, Regression, Mental Health, Phenotype, polygenic risk scores, Mixed model, Multiple Sclerosis, Genotype, Quantitative Trait Loci, polygenic risk score, schizophrenia, GWAS, Discovery, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetics, Humans, p-value, Pruning (decision trees), Polymorphism, Genome-Wide Association Study, Schizophrenia, Models, Theoretical, 030304 developmental biology, genome-wide association study, and Risk of Inherited Variants in Breast Cancer (DRIVE) study, Brain Disorders, Data set, schizophrenia, Sample size determination, polygenic risk score, Polygenic risk score, 030217 neurology & neurosurgery, linkage disequilibrium
Abstract: Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R-2 increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase. Refereed/Peer-reviewed
Published: 2015

39. Brief Report: Phenotypic Differences and their Relationship to Paternal Age and Gender in Autism Spectrum Disorder

Author: Esther Vierck and Jeremy M. Silverman
Subjects: Adult, Male, Proband, Adaptive behavior, Intelligence quotient, Autism Spectrum Disorder, Paternal age, Regression analysis, Middle Aged, medicine.disease, Phenotype, Paternal Age, Developmental psychology, Young Adult, Sex Factors, Autism spectrum disorder, Developmental and Educational Psychology, medicine, Humans, Autism, Female, Child, Psychology
Abstract: Two modes of inheritance have been proposed in autism spectrum disorder, transmission though pre-existing variants and de novo mutations. Different modes may lead to different symptom expressions in affected individuals. De novo mutations become more likely with advancing paternal age suggesting that paternal age may predict phenotypic differences. To test this possibility we measured IQ, adaptive behavior, and autistic symptoms in 830 probands from simplex families. We conducted multiple linear regression analysis to estimate the predictive value of paternal age, maternal age, and gender on behavioral measures and IQ. We found a differential effect of parental age and sex on repetitive and restricted behaviors. Findings suggest effects of paternal age on phenotypic differences in simplex families with ASD.
Published: 2014

40. Association of Apolipoprotein E-e4 and Dementia Declines with Age

Author: Lara Mora Villalobos, José R. Carrión-Baralt, Daniel Valerio, Patricia Bolaños-Palmieri, Jeremy M. Silverman, Michal Schnaider Beeri, James Schmeidler, Jaime Fornaguera, and Henriette Raventós
Subjects: Costa Rica, Male, Apolipoprotein E, Gerontology, Cognitive aging, Aging, Genotype, Apolipoprotein B, Apolipoprotein E4, Oldest-old, Article, Group interaction, medicine, Humans, Dementia, Apolipoprotein e4, Association (psychology), Genetic Association Studies, Aged, Aged, 80 and over, biology, Case-control study, medicine.disease, Psychiatry and Mental health, Case-Control Studies, Successful cognitive aging, biology.protein, Dementia risk factors, Female, Geriatrics and Gerontology, Psychology
Abstract: To study the association of dementia with apolipoprotein E-e4 (APOE-e4) and its interaction with age in a nonagenarian Costa Rican group (N-sample) and a general elderly contrast group (GE-sample). In both case-control studies, participants were cognitively intact or diagnosed with dementia. The N-sample (N = 112) was at least age 90 years; the GE-sample (N = 98) was at least age 65 years. Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93 years) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging. Universidad de Costa Rica/[]/UCR/Costa Rica Fogarty International Center/[]/NIH/Estados Unidos National Institute on Aging/[R21TW009258]/NIH/Estados Unidos Alzheimer’s Association/[]//Estados Unidos UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN) UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicina UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM) UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biología
Published: 2014

41. Age at first birth in women is genetically associated with increased risk of schizophrenia

Author: Fritz Zimprich, Manuel Mattheisen, Edward M. Scolnick, Ayman H. Fanous, Henrik B. Rasmussen, Steven A. McCarroll, Ingrid Agartz, Carmel M. Loughland, Aiden Corvin, Ann Olincy, Anders D. Børglum, F. Anthony O'Neill, T. Scott Stroup, Elizabeth Bevilacqua, Sandra Meier, Ulrich Schall, Jouko Lönnqvist, Jianxin Shi, C. Robert Cloninger, Judit Bene, Veikko Salomaa, George N. Papadimitriou, Milica Pejovic-Milovancevic, Béla Melegh, Kari Stefansson, Brendan Bulik-Sullivan, Janis Klovins, Enrico Domenici, Sibylle G. Schwab, Dai Wang, Assen Jablensky, Mari Nelis, Sang Yun Oh, Peter Holmans, Aaron R. Wolen, Hualin Simon Xi, Eric Strengman, Bryan J. Mowry, Michael Gill, Kung Yee Liang, William Byerley, Rolf Adolfsson, Hugh Gurling, Joseph I. Friedman, Andrew Pocklington, Brien P. Riley, Engilbert Sigurdsson, Benjamin M. Neale, Miaoxin Li, Michael Davidson, Bernard Lerer, Michele T. Pato, Xuebin Zheng, Patrick F. Sullivan, Frans Henskens, Madeline Alexander, Andrew M. McIntosh, Inez Myin-Germeys, Draga Toncheva, Liene Nikitina-Zake, Kenneth S. Kendler, Carin J. Meijer, Robin M. Murray, Richard E. Straub, Ann E. Pulver, Menachem Fromer, Derek W. Morris, Douglas M. Ruderfer, Mythily Subramaniam, Paul Cormican, Lyudmila Georgieva, Giulio Genovese, Brion S. Maher, Stanley V. Catts, David St Clair, Robert W. McCarley, David Cohen, Nancy G. Buccola, Dan Rujescu, Carlos N. Pato, Kristin K. Nicodemus, Josef Frank, Claudine Laurent, Dominique Campion, Guiyan Ni, James L. Kennedy, Sena Karachanak-Yankova, Nicholas John Craddock, Peter M. Visscher, Valentina Escott-Price, Jeffrey A. Lieberman, Deborah A. Nertney, Bertram Müller-Myhsok, Marcella Rietschel, Dimitris Dikeos, Stephanie Godard, Stephanie Williams, Andres Metspalu, John L. Waddington, Sophie E. Legge, Roel A. Ophoff, Jonathan Pimm, Richard Bruggeman, Tim B. Bigdeli, Gerald Nestadt, Mark Weiser, Kieran C. Murphy, Eric F.C. Cheung, Kang Sim, Jordan W. Smoller, David J. Kavanagh, Inge Joa, Jens R. Wendland, Thomas G. Schulze, Richard A. Belliveau, Sarah E. Bergen, Ditte Demontis, David Curtis, Todd Lencz, Danielle Posthuma, René S. Kahn, Lili Milani, Randy L. Buckner, Jianjun Liu, Petr Slominsky, Wiepke Cahn, Hana Kuzelova-Ptackova, Sergi Papiol, Tune H. Pers, Stephan Ripke, Rita M. Cantor, Ariel Darvasi, Christina M. Hultman, Larry J. Seidman, Eli A. Stahl, David A. Collier, Michael Conlon O'Donovan, Svetlana A. Limborska, James T.R. Walters, Farooq Amin, Noa Carrera, Ronald Y.L. Chen, Pablo V. Gejman, Joel N. Hirschhorn, Zita Ausrele Kucinskiene, Michael John Owen, Ina Giegling, Stephanie H. Witt, Timothy G. Dinan, Margot Albus, Wei Cheng, Marian L. Hamshere, Markus M. Nöthen, Thomas Werge, Guiqing Cai, Raquelle I. Mesholam-Gately, Annette M. Hartmann, Ingrid Melle, Ole A. Andreassen, Preben Bo Mortensen, Hannelore Ehrenreich, Tiina Paunio, James A. Knowles, Pak C. Sham, Marion Friedl, Teimuraz Silagadze, Dermot Walsh, Emily H. M. Wong, Igor Nenadic, Matthew C. Keller, John Powell, Naomi R. Wray, Patricia T. Michie, Bradley T. Webb, Lude Franke, Mark Hansen, Masashi Ikeda, Sven Cichon, Elvira Bramon, Frank Dudbridge, Erik G. Jönsson, Annelie Nordin, Wolfgang Maier, Peter Eichhammer, Christian R. Schubert, J. Mallet, Jacob Gratten, Andrey Khrunin, Jacqueline I. Goldstein, Panos Roussos, Pamela Sklar, Diana O. Perkins, Srdjan Djurovic, Phil Lee, Elodie Drapeau, Douglas F. Levinson, Nadine Cohen, Luba Kalaydjieva, Brandon Wormley, Tao Li, Tõnu Esko, Alexander Richards, Srihari Gopal, Jubao Duan, Anil K. Malhotra, Elisabeth Stögmann, Gary Donohoe, Kimberly Chambert, Sara Marsal, Hreinn Stefansson, Jo Knight, Ole Mors, Per Hoffmann, Dieter B. Wildenauer, James J. Crowley, Srinivas Thirumalai, Vahram Haroutunian, A. Hofman, Hailiang Huang, Thomas Hansen, Daniel R. Weinberger, Andrew McQuillin, Vaughan J. Carr, Vaidutis Kučinskas, Jimmy Lee Chee Keong, Digby Quested, Aarno Palotie, Robert Freedman, Hon-Cheong So, Jennifer L. Moran, Donald W. Black, Mark Reimers, Abraham Reichenberg, Jurgen Del Favero, Paola Giusti-Rodríguez, Tracey L. Petryshen, Olli Pietiläinen, Franziska Degenhardt, Laurent Essioux, Esben Agerbo, Qiang Wang, Jana Strohmaier, Siow Ann Chong, Johan G. Eriksson, Martin Begemann, Younes Mokrab, Colm McDonald, Silviu Alin Bacanu, Martilias S. Farrell, Christos Pantelis, Kai How Farh, Line Olsen, Naser Durmishi, Antonio Julià, Stefan Herms, Qingqin S. Li, Bettina Konte, George Kirov, Rodney J. Scott, Nelson B. Freimer, Mads V. Hollegaard, Shaun Purcell, Erik Söderman, Dragan M. Svrakic, Patrik K. E. Magnusson, Douglas Blackwood, Jin P. Szatkiewicz, Sang Hong Lee, Yunjung Kim, Colm O'Dushlaine, Morten Mattingsdal, Jim van Os, Sarah Tosato, Milan Macek, Joshua L. Roffman, Jan Lubinski, Eadbhard O'Callaghan, Juha Karjalainen, Vera Golimbet, Anna K. Kähler, Clement C. Zai, Nigel Williams, Joseph D. Buxbaum, Laura Nisenbaum, Eric Y.H. Chen, David M. Hougaard, Jaana Suvisaari, Chris C. A. Spencer, Alan R. Sanders, Alkes L. Price, Vihra Milanova, Juha Veijola, Christian Hammer, Raymond C.K. Chan, Stacy Steinberg, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Kenneth L. Davis, Lieuwe de Haan, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Kučinskas, Vaidutis, Kučinskienė, Zita Aušrelė, Ni, Guiyan, Gratten, Jacob, Wray, Naomi R, Lee, Sang Hong, Germeys, Inez, Complex Trait Genetics, Háskóli Íslands, University of Iceland, Child and Adolescent Psychiatry / Psychology, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University Management, Department of Psychiatry, Center for Population, Health and Society, Department of Public Health, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, and Genomics of Neurological and Neuropsychiatric Disorders
Subjects: 0301 basic medicine, Multifactorial Inheritance, PATERNAL-AGE, 3124 Neurology and psychiatry, COMMON SNPS, fluids and secretions, 0302 clinical medicine, CHILD, Risk Factors, Pregnancy, 2.1 Biological and endogenous factors, Medicine, Aetiology, Pediatric, PROPORTION, Schizophrenia Working Group of the Psychiatric Genomics Consortium, 0303 health sciences, Multidisciplinary, PSYCHIATRIC-DISORDERS, BIPOLAR DISORDER, Biobank, 3. Good health, AFB, Mental Health, Schizophrenia, Female, Erfðarannsóknir, Psychosocial, TRAITS, schizophrenia, age at birth, AFB, Maternal Age, Adult, age at first birth in women, genetic association, Offspring, Science, Genetic correlation, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Geðklofi, Genetics, age at birth, Humans, Genetic Predisposition to Disease, Bipolar disorder, General, Biology, Genetic association study, 030304 developmental biology, Genetic association, business.industry, Genetic heterogeneity, Prevention, average aged parents, Parturition, SCORE REGRESSION, bacterial infections and mycoses, medicine.disease, Mental health, Brain Disorders, respiratory tract diseases, schizophrenia, Good Health and Well Being, 030104 developmental biology, younger and older parents, DE-NOVO MUTATIONS, ddc:000, Human medicine, business, 030217 neurology & neurosurgery, Demography
Abstract: Publisher's version (útgefin grein), Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is −0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health., This research is supported by the Australian National Health and Medical Research Council (1080157, 1087889, 1103418, 1127440), and the Australian Research Council (DP160102126, FT160100229). This research has been conducted using the UK Biobank Resource. UK Biobank (http://www.ukbiobank.ac.uk) Research Ethics Committee (REC) approval number is 11/NW/0382. Our reference number approved by UK Biobank is 14575.
Published: 2017

42. OLDER VETERANS WITH TYPE 2 DIABETES: A1C AND COGNITIVE FUNCTION

Author: M. Schnaider-Beeri, James Schmeidler, Pearl G. Lee, Jeremy M. Silverman, R. West, Mary Sano, Neil B. Alexander, and Elizabeth Guerrero-Berroa
Subjects: Gerontology, Health (social science), business.industry, Cognition, Type 2 diabetes, medicine.disease, Health Professions (miscellaneous), humanities, Abstracts, Text mining, medicine, Life-span and Life-course Studies, business, health care economics and organizations
Abstract: Poor glycemic control (i.e., high A1c) among older adults with type 2 diabetes (DM) is associated with high risk of cognitive impairment across various domains of cognitive assessments. Older Veterans with DM have not been well studied. We hypothesized that high A1c is associated with worse executive function among older Veterans with DM.
Published: 2017

43. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

Author: Cristina Cereda, Jurjen J. Luykx, Sandra Meier, Derek W. Morris, Douglas M. Ruderfer, Mythily Subramaniam, Paul Cormican, Lyudmila Georgieva, John Landers, Silvana Penco, Marian L. Hamshere, Frank Dudbridge, Mari Nelis, Dick Schijven, Jimmy Lee, Sarah E. Bergen, Alessandro Padovani, Nicholas W. Wood, Meraida Polak, Hannelore Ehrenreich, Nancy G. Buccola, Noa Carrera, Stefan Herms, Panos Roussos, Marion Friedl, Teimuraz Silagadze, Jim van Os, Annette M. Hartmann, Ole A. Andreassen, R. Jeroen Pasterkamp, Sibylle G. Schwab, Aleksey Shatunov, Eli A. Stahl, David A. Collier, Farooq Amin, Michael Conlon O'Donovan, Guiqing Cai, Kung-Yee Liang, Denis C. Bauer, Charles Curtis, Brion S. Maher, Ashley R. Jones, Sara L. Pulit, Sarah Tosato, Milan Macek, Vivianna M. Van Deerlin, Vincenzo Silani, Pietro Fratta, Bettina Konte, Rosanna Tortelli, Dan Rujescu, T. Scott Stroup, Elizabeth Bevilacqua, Christian Lunetta, Bradley T. Webb, Christophe Tzourio, Patrick Vourc'h, Joel N. Hirschhorn, Gilbert Bensimon, Timothy G. Dinan, Thomas G. Schulze, Richard A. Belliveau, Daniel R. Weinberger, Andrew McQuillin, Qingqin S. Li, Orla Hardiman, Claudine Laurent, Masashi Ikeda, Tim Kahlke, Rodney J. Scott, Frans Henskens, Tune H. Pers, Wolfgang Lieb, Christian Hammer, Elvira Bramon, Hana Kuzelova-Ptackova, Raquelle I. Mesholam-Gately, Ingrid Melle, Nadine Cohen, David Cohen, Nazli Basak, Elisabeth Stögmann, Nelson B. Freimer, Peter Eichhammer, J. Mallet, Preben Bo Mortensen, Robert H. Brown, Wouter van Rheenen, Roberto Del Bo, Dai Wang, Laurent Essioux, Larry J. Seidman, Hreinn Stefansson, Erik G. Jönsson, Mads V. Hollegaard, Raymond C.K. Chan, Susana Pinto, Alexander Richards, Jubao Duan, Peter Holmans, George Kirov, Pablo V. Gejman, Philippe Amouyel, Stephanie Godard, Dieter B. Wildenauer, Martina Wiedau-Pazos, Stacy Steinberg, Ole Mors, Andres Metspalu, Rolf Adolfsson, Shaun Purcell, Hugh Gurling, Joseph I. Friedman, Erik Söderman, Mark Weiser, Giacomo P. Comi, James A. Knowles, Peter M. Andersen, Brien P. Riley, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Digby Quested, Srinivas Thirumalai, Ulrich Schall, Jan Lubinski, Dragan M. Svrakic, Aaron R. Wolen, S. Hong Lee, Andrew Pocklington, Bernard Lerer, Vahram Haroutunian, Matthew C. Kiernan, Kenneth L. Davis, Assen Jablensky, William Byerley, Karol Estrada, Aarno Palotie, Cinzia Tiloca, Eadbhard O'Callaghan, Perry T.C. van Doormaal, Colm McDonald, Federico Casale, Thomas Meitinger, Robert Freedman, Gerome Breen, Milena Blagojevic-Radivojkov, Ian P. Blair, Ann E. Pulver, Jan H. Veldink, Giancarlo Logroscino, Miaoxin Li, Abraham Reichenberg, Esben Agerbo, Siddharthan Chandran, Patrik K. E. Magnusson, Andrew M. McIntosh, Gianni Sorarù, Maura Brunetti, Xuebin Zheng, Madeline Alexander, James L. Kennedy, Douglas Blackwood, Menachem Fromer, Martilias S. Farrell, Alan R. Sanders, Dominic B. Rowe, Alexis Brice, Jonathan Pimm, Emily H. M. Wong, Jana Strohmaier, André G. Uitterlinden, Andrea Calvo, Carsten Drepper, John Q. Trojanowski, Marcella Rietschel, Siow Ann Chong, Karen E. Morrison, Sang-Yun Oh, Laura Nisenbaum, Margaret O'Brien, Alkes L. Price, Carin J. Meijer, Michael Davidson, John Powell, Petr Slominsky, Wiepke Cahn, Cinzia Gellera, Vihra Milanova, Peter M. Visscher, Patricia T. Michie, Dimitris Dikeos, Jianxin Shi, Veikko Salomaa, Philip Van Damme, James J. Crowley, Younes Mokrab, Valentina Escott-Price, Jesus S. Mora, Stanley V. Catts, David St Clair, Bernhard Landwehrmeyer, John Hardy, Kristin K. Nicodemus, Dominique Campion, Juha Veijola, Wim Robberecht, Thomas Meyer, Peter Lichtner, Christos Pantelis, Markus Weber, Nilo Riva, Jin P. Szatkiewicz, Michele T. Pato, Cinzia Bertolin, Frank P. Diekstra, Simon Arcuti, Bryan J. Mowry, Hon-Cheong So, Adriano Chiò, Viviana Pensato, Yunjung Kim, Jean-François Dartigues, Zita Ausrele Kucinskiene, Inez Myin-Germeys, Jaana Suvisaari, Sophie E. Legge, Roel A. Ophoff, Philippe Corcia, Gerald Nestadt, Stephan Ripke, Kuang Lin, Paola Giusti-Rodríguez, Michael John Owen, Chris C. A. Spencer, Safa Saker-Delye, Robert W. McCarley, Kimberley D. Chambert, Brandon Wormley, Isabella Fogh, Mamede de Carvalho, Pamela J. Shaw, Tõnu Esko, Ronald Y. L. Chan, Jianjun Liu, Tim B. Bigdeli, Christian R. Andres, David M. Hougaard, Michael Gill, Ammar Al-Chalabi, Colm O'Dushlaine, Rick A.A. van der Spek, Gary Donohoe, Tao Li, Jonathan D. Glass, Christopher Shaw, Draga Toncheva, Leonard H. van den Berg, Liene Nikitina-Zake, Morten Mattingsdal, François Salachas, Andrey Khrunin, Line Olsen, Jochen H. Weishaupt, Jo Knight, Katie Sidle, Filip Eftimov, Massimiliano Filosto, Russell L. McLaughlin, Pak C. Sham, Joshua L. Roffman, Thomas Hansen, Naser Durmishi, Deborah A. Nertney, Juha Karjalainen, Robert Swingler, Ditte Demontis, Vaidutis Kučinskas, Jennifer L. Moran, Leo McCluskey, Donald W. Black, Eric F.C. Cheung, Qiang Wang, Olli Pietilainen, Vera Golimbet, Anna K. Kähler, Clement C. Zai, Nigel Williams, Annelie Nordin, Wolfgang Maier, Bradley N. Smith, Ettore Beghi, Rosa Capozzo, Garth A. Nicholson, Markus M. Nöuthen, Jordan W. Smoller, Eric Y.H. Chen, Joseph D. Buxbaum, Letizia Mazzini, Andrea Malaspina, Antonio Julià, Stephanie Williams, Tracey L. Petryshen, Christine Payan, Johan G. Eriksson, Carmel M. Loughland, Elodie Drapeau, Lieuwe de Haan, Martin Begemann, Lukas Tittmann, Franziska Degenhardt, Mark Reimers, Jurgen Del Favero, Jacqueline I. Goldstein, Annelot M. Dekker, Sergi Papiol, Svetlana A. Limborska, René S. Kahn, Shuna Colville, Kelly L. Williams, Pamela Sklar, Diana O. Perkins, Lili Milani, Ayman H. Fanous, Nicola Ticozzi, Fernando Rivadeneira, Marianne de Visser, P. Nigel Leigh, James T.R. Walters, Josef Frank, Aiden Corvin, Silviu Alin Bacanu, John L. Waddington, Stephanie H. Witt, Tiina Paunio, Margot Albus, Catherine Lomen-Hoerth, Sara Marsal, Per Hoffmann, David Curtis, Cindy Maurel, Todd Lencz, Orietta Pansarasa, Manuel Mattheisen, Anneke J. van der Kooi, A. Hofman, Dermot Walsh, Hailiang Huang, Ann Olincy, Anders D. Børglum, Ricardo Rojas-García, William Sproviero, Albert C. Ludolph, Edward M. Scolnick, Danielle Posthuma, George N. Papadimitriou, Michael A. van Es, Fritz Zimprich, F. Anthony O'Neill, Lude Franke, Jouko Lönnqvist, Daniel G. Bradley, Sven Cichon, Susanna Abdulla, Kristel R. van Eijk, Ingrid Agartz, Elisabetta Pupillo, Milica Pejovic-Milovancevic, Antonia Ratti, Henrik B. Rasmussen, Kari Stefansson, Brendan Bulik-Sullivan, Béla Melegh, Stéphanie Millecamps, Janis Klovins, Enrico Domenici, Michael Sendtner, Kai-How Farh, Randy L. Buckner, Albert Hofman, Benjamin M. Neale, Naomi R. Wray, An Goris, Kang Sim, Lauren Elman, Giulio Genovese, Jens R. Wendland, Rita M. Cantor, Ariel Darvasi, Christina M. Hultman, Sandra D'Alfonso, Cristina Moglia, Carlos N. Pato, Sena Karachanak-Yankova, Nicholas John Craddock, Richard W. Orrell, Richard Bruggeman, Kenneth S. Kendler, Alan M. Pittman, Robin M. Murray, Richard E. Straub, Cathryn M. Lewis, Srdjan Djurovic, Vincent Meininger, Jeffrey A. Lieberman, Bertram Müller-Myhsok, Phil Lee, David J. Kavanagh, Srihari Gopal, Igor Nenadic, Matthew C. Keller, Christian R. Schubert, Jacob Gratten, Alexandra Durr, Roger Pamphlett, Douglas F. Levinson, Luba Kalaydjieva, Chiara Zecca, Anil K. Malhotra, Andre Franke, Vaughan J. Carr, Steven A. McCarroll, C. Robert Cloninger, Judit Bene, Ina Giegling, Wei Cheng, Hualin Simon Xi, Thomas Werge, Eric Strengman, Susanne Petri, Engilbert Sigurdsson, Mark Hansen, Patrick F. Sullivan, Kieran C. Murphy, Inge Joa, Complex Trait Genetics, McLaughlin, Russell L, Schijven, Dick, Van Rheenen, Wouter, Van Eijk, Kristel R, O'Brien, Margaret, Kahn, René S, Ophoff, Roel A, Goris, An, Bradley, Daniel G, Al-Chalabi, Ammar, Van Den Berg, Leonard H, Luykx, Jurjen J, Hardiman, Orla, Veldink, Jan H, Lee, S Hong, Project MinE GWAS Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Kučinskas, Vaidutis, Kučinskienė, Zita Aušrelė, Other departments, Neurology, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Schizophrenia Working Group of the Psychiatric Genomics Consortiumz, Germeys, Inez, Robberecht, Wim, and Van Damme, Philip
Subjects: 0301 basic medicine, Oncology, Genetics and Molecular Biology (all), Linkage disequilibrium, Multifactorial Inheritance, General Physics and Astronomy, Genome-wide association study, Comorbidity, VARIANTS, Neurodegenerative, Biochemistry, DISEASE, 3124 Neurology and psychiatry, Linkage Disequilibrium, Cohort Studies, 0302 clinical medicine, Genetics research, Odds Ratio, 2.1 Biological and endogenous factors, Amyotrophic lateral sclerosis, Aetiology, ARCHITECTURE, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Multidisciplinary, Chemistry (all), Motor neuron disease, Schizophrenia, BIPOLAR DISORDER, Single Nucleotide, Serious Mental Illness, 3. Good health, Mental Health, RC0346, motor neuron disease, Project MinE GWAS Consortium, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Science, European Continental Ancestry Group, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, White People, 03 medical and health sciences, Physics and Astronomy (all), Rare Diseases, SDG 3 - Good Health and Well-being, Clinical Research, Internal medicine, MD Multidisciplinary, mental disorders, medicine, Genetics, Journal Article, Humans, Genetic Predisposition to Disease, Family, Bipolar disorder, GENOME-WIDE ASSOCIATION, Polymorphism, Biology, METAANALYSIS, business.industry, Amyotrophic Lateral Sclerosis, Human Genome, Case-control study, 3112 Neurosciences, Neurosciences, General Chemistry, Odds ratio, medicine.disease, R1, Brain Disorders, 030104 developmental biology, genetics research, Case-Control Studies, RC0321, Linear Models, PLEIOTROPY, Human medicine, 3111 Biomedicine, Biochemistry, Genetics and Molecular Biology (all), ALS, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6; P=1 × 10−4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10−7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08–1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies., Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.
Published: 2017

44. Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia

Author: Larry J. Siever, Melissa Tarasenko, Joyce Sprock, Catherine A. Sugar, Gerhard Hellemann, Michael F. Green, Monica E. Calkins, Tiffany A. Greenwood, Ruben C. Gur, Debby W. Tsuang, Larry J. Seidman, Jeremy M. Silverman, Raquel E. Gur, Laura C. Lazzeroni, Gregory A. Light, Alexandra L. Shiluk, Allen D. Radant, William S. Stone, David L. Braff, Bruce I. Turetsky, Michael L. Thomas, Keith H. Nuechterlein, Neal R. Swerdlow, and Ming T. Tsuang
Subjects: Adult, Male, medicine.medical_specialty, education, Schizoaffective disorder, Contingent Negative Variation, Models, Psychological, Verbal learning, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Models, Clinical Research, Behavioral and Social Science, medicine, Humans, Psychology, Psychiatry, Scale for the Assessment of Negative Symptoms, Psychiatric Status Rating Scales, Other Medical and Health Sciences, Prevention, Auditory Perceptual Disorders, Neurosciences, Wechsler Adult Intelligence Scale, Social Behavior Disorders, Cognition, Middle Aged, medicine.disease, Serious Mental Illness, 030227 psychiatry, Brain Disorders, Psychiatry and Mental health, Cross-Sectional Studies, Mental Health, Psychotic Disorders, Schizophrenia, Endophenotype, Psychological, Schizophrenic Psychology, Female, Cognitive Sciences, Cognition Disorders, Psychosocial, 030217 neurology & neurosurgery
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
Published: 2017

45. The TOMM40 poly-T rs10524523 variant is associated with cognitive performance among non-demented elderly with type 2 diabetes

Author: Itzik Cooper, Michal Schnaider Beeri, Lior Greenbaum, Ann M. Saunders, Mary Sano, Irit Lubitz, Efrat Kravitz, Jeremy M. Silverman, Allen D. Roses, Michael W. Lutz, Anthony Heymann, and Ramit Ravona Springer
Subjects: Male, Apolipoprotein E, Oncology, Linkage disequilibrium, medicine.medical_specialty, Genotype, Type 2 diabetes, Neuropsychological Tests, Polymorphism, Single Nucleotide, Article, Apolipoproteins E, Internal medicine, Diabetes mellitus, Mitochondrial Precursor Protein Import Complex Proteins, medicine, Humans, Genetic Predisposition to Disease, Pharmacology (medical), Effects of sleep deprivation on cognitive performance, Allele, Genetic Association Studies, Biological Psychiatry, Pharmacology, Genetics, Membrane Transport Proteins, Cognition, medicine.disease, Psychiatry and Mental health, Diabetes Mellitus, Type 2, Neurology, Female, Neurology (clinical), Cognition Disorders, Psychology
Abstract: The variable length poly-T, rs10524523 ('523') located within the TOMM40 gene, was recently associated with several phenotypes of cognitive function. The short (S) allele is associated with later AD onset age and better cognitive performance, compared to the longer alleles (long and very-long (VL)). There is strong linkage disequilibrium between variants in the TOMM40 and APOE genes. In this study, we investigated the effect of '523' on cognitive performance in a sample of cognitively normal Jewish elderly with type 2 diabetes, a group at particularly high risk for cognitive impairment. Using a MANCOVA procedure, we compared homozygous carriers of the S/S allele (N=179) to carriers of the VL/VL allele (N=152), controlling for demographic and cardiovascular covariates. The S/S group performed better than the VL/VL group (p=0.048), specifically in the executive function (p=0.04) and episodic memory (p=0.050) domains. These results suggest that previous findings of an association of the TOMM40 short allele with better cognitive performance, independently from the APOE variant status, are pertinent to elderly with diabetes.
Published: 2014

46. Decreased Motor Function Is Associated with Poorer Cognitive Function in Elderly with Type 2 Diabetes

Author: Rachel Preiss, Ramit Ravona-Springer, Elizabeth Guerrero-Berroa, Hadas Hoffman, Mary Sano, Keren Koifmann, Jeremy M. Silverman, Michal Schnaider Beeri, James Schmeidler, and Anthony Heymann
Subjects: medicine.medical_specialty, Cognitive Neuroscience, Poison control, Audiology, lcsh:Geriatrics, lcsh:RC346-429, Developmental psychology, Grip strength, Elderly, Cognition, Memory, Dementia, medicine, Original Research Article, Association (psychology), Episodic memory, Motor function, lcsh:Neurology. Diseases of the nervous system, Working memory, Type 2 diabetes, medicine.disease, Psychiatry and Mental health, lcsh:RC952-954.6, Categorization, Psychology, human activities
Abstract: Background/Aims: Impaired motor function has been associated with cognitive impairment and dementia, but this relationship is poorly understood in elderly with type 2 diabetes (T2D). We thus investigated it in a large sample (n = 726) of cognitively normal elderly with T2D. Methods: In this cross-sectional study, hierarchical linear regressions assessed correlations of 3 motor measures (timed walk, grip strength, and self-reported motor difficulties) with episodic memory, attention/working memory, semantic categorization, executive function, and overall cognition controlling for demographics. Results: Longer timed walk and weaker grip strength were associated with poorer performance in all cognitive domains except episodic memory. Conclusions: Associations of motor and cognitive functions in T2D and non-T2D samples are consistent. A lack of association of motor function with episodic memory may suggest non-Alzheimer's disease-related underlying mechanisms.
Published: 2014

47. Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

Author: Larry J. Siever, Raquel E. Gur, Ruben C. Gur, Neal R. Swerdlow, Ming T. Tsuang, Larry J. Seidman, Allen D. Radant, William S. Stone, Joyce Sprock, Monica E. Calkins, Keith H. Nuechterlein, Gregory A. Light, Amrita Ray, Debby W. Tsuang, Tiffany A. Greenwood, Bruce I. Turetsky, Jeremy M. Silverman, Laura C. Lazzeroni, David L. Braff, Michael F. Green, and Catherine A. Sugar
Subjects: Male, Proband, Multi-site, Medical and Health Sciences, 2.1 Biological and endogenous factors, Aetiology, Prepulse inhibition, Psychiatry, Genetics, Startle, Multi site, Middle Aged, Sensory Gating, Endophenotype, Psychiatry and Mental health, Mental Health, medicine.anatomical_structure, Schizophrenia, Schizophrenic Psychology, Female, Psychology, Clinical psychology, Adult, Adolescent, Single-nucleotide polymorphism, behavioral disciplines and activities, Article, Young Adult, Clinical Research, mental disorders, medicine, Humans, Biological Psychiatry, Aged, Psychiatric Status Rating Scales, Analysis of Variance, Sensory gating, Psychology and Cognitive Sciences, Neurosciences, Neural Inhibition, Interim analysis, medicine.disease, Brain Disorders, Acoustic Stimulation, human activities
Abstract: Background: Startle 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. Methods: Eyeblink 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. Results: 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p. = 0.0005) and sex (p. . schizophrenia 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. Discussion: The 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. © 2013 Elsevier B.V.
Published: 2014

48. Hemoglobin A

Author: Ramit, Ravona-Springer, Anthony, Heymann, James, Schmeidler, Erin, Moshier, Elizabeth, Guerrero-Berroa, Laili, Soleimani, Mary, Sano, Derek, Leroith, Rachel, Preiss, Ruth, Tzukran, Jeremy M, Silverman, and Michal Schnaider, Beeri
Subjects: Blood Glucose, Glycated Hemoglobin, Male, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Depression, Humans, Female, Registries, Israel, Epidemiology/Health Services Research, Aged
Abstract: OBJECTIVE This study aimed to analyze the relationship of variability in hemoglobin A1c (HbA1c) over years with subsequent depressive symptoms. RESEARCH DESIGN AND METHODS Subjects (n = 837) were participants of the Israel Diabetes and Cognitive Decline (IDCD) study, which aimed to examine the relationship of characteristics of long-term type 2 diabetes with cognitive decline. All pertain to a diabetes registry established in 1998, which contains an average of 18 HbA1c measurements per subject. The results presented here are based on the IDCD baseline examination. Symptoms of depression were assessed using the 15-item version of the Geriatric Depression Scale (GDS). To quantify the association between variability in glycemic control (measured as the SD of HbA1c measurements [HbA1c-SD]) since 1998 with the number of depression symptoms at IDCD baseline, incidence rate ratios (IRRs) and corresponding 95% CIs were estimated via negative binomial regression modeling and used to account for the overdispersion in GDS scores. RESULTS Subjects’ ages averaged 72.74 years (SD 4.63 years), and the mean number of years in the diabetes registry was 8.7 (SD 2.64 years). The mean GDS score was 2.16 (SD 2.26); 10% of subjects had a GDS score ≥6, the cutoff for clinically significant depression. Mean HbA1c significantly correlated with HbA1c-SD (r = 0.6625; P < 0.0001). The SD, but not the mean, of HbA1c measurements was significantly associated with the number of subsequent depressive symptoms. For each additional 1% increase in HbA1c-SD, the number of depressive symptoms increased by a factor of 1.31 (IRR = 1.31 [95% CI 1.03–1.67]; P = 0.03). CONCLUSIONS Variability in glycemic control is associated with more depressive symptoms.
Published: 2016

49. S209. Genome-Wide Association of Endophenotypes for Schizophrenia From the Consortium On the Genetics of Schizophrenia (COGS) Study

Author: Debby W. Tsuang, Laura C. Lazzeroni, Ann Olincy, Gregory A. Light, Neal R. Swerdlow, Monica E. Calkins, Ming T. Tsuang, Larry J. Siever, Bruce I. Turetsky, Michael F. Green, Tiffany A. Greenwood, Jeremy M. Silverman, Catherine A. Sugar, David L. Braff, Allen D. Radant, William S. Stone, Keith H. Nuechterlein, Robert Freedman, Ruben C. Gur, Larry J. Seidman, and Raquel E. Gur
Subjects: 0301 basic medicine, Genetics, 03 medical and health sciences, 030102 biochemistry & molecular biology, Schizophrenia (object-oriented programming), Endophenotype, Genome-wide association study, Biology, Biological Psychiatry
Published: 2018

50. Age, gender, and education are associated with cognitive performance in an older Israeli sample with type 2 diabetes

Author: Elizabeth Guerrero-Berroa, Ramit Ravona-Springer, Hadas Hoffman, Mary Sano, Jeremy M. Silverman, Michal Schnaider Beeri, James Schmeidler, Rachel Preiss, Keren Koifmann, and Anthony Heymann
Subjects: Gerontology, Higher education, business.industry, Neuropsychology, Cognition, Disease, Type 2 diabetes, medicine.disease, Psychiatry and Mental health, medicine, Cognitive skill, Effects of sleep deprivation on cognitive performance, Geriatrics and Gerontology, Cognitive decline, business, Psychology
Abstract: Objective To evaluate the relationships of age, education, and gender with performance on neuropsychological tests in a cognitively intact, older Israeli sample with type 2 diabetes (T2D). Methods We examined 862 participants, 65–84 years old, enrolled in the Israel Diabetes and Cognitive Decline study. Multiple regression assessed associations of performance on 17 neuropsychological tests, including the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery, with age, education, and gender. Results Higher education and younger age were consistently associated with better performance. Women outperformed men on all memory tasks; men outperformed women on two non-verbal measures. These patterns of demographic associations with cognitive performance were very similar to those of US cohorts. Conclusions In a cognitively intact, older Israeli sample with T2D, better test performance is associated primarily with higher education, followed by younger age and gender differences. Although T2D is associated with cognitive deficits, it recapitulates the patterns of relationships between cognitive performance and demographic characteristics seen in non-T2D diabetic samples. Copyright © 2013 John Wiley & Sons, Ltd.
Published: 2013

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