Junghee Lee1, Michael F Green2, Monica E Calkins3, Tiffany A Greenwood4, Raquel E Gur3, Ruben C Gur3, Laura C Lazzeroni5, Gregory A Light6, Keith H Nuechterlein7, Allen D Radant8, Larry J Seidman9, Larry J Siever10, Jeremy M Silverman10, Joyce Sprock6, William S Stone9, Catherine A Sugar11, Neal R Swerdlow4, Debby W Tsuang8, Ming T Tsuang12, Bruce I Turetsky3, David L Braff6. 1. Department of Psychiatry and Biobehavioral Science, Geffen School of Medicine, University of California Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States. Electronic address: jungheelee@ucla.edu. 2. Department of Psychiatry and Biobehavioral Science, Geffen School of Medicine, University of California Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States. 3. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States. 4. Department of Psychiatry, University of California San Diego, La Jolla, CA, United States. 5. Department of Psychiatry and Behavioral Science, Stanford University, Stanford, CA United States; Department of Pediatrics, Stanford University, Stanford, CA, United States. 6. Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VISN22, Mental Illness Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, United States. 7. Department of Psychiatry and Biobehavioral Science, Geffen School of Medicine, University of California Los Angeles, CA, United States. 8. Department of Psychiatry and Behavioral Science, University of Washington, Seattle, WA, United States; VA Puget Sound Healthcare System, Seattle, WA, United States. 9. Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Massachusetts Mental Health Center Public Psychiatry Devision of the Beth Israel Deaconess Medical Center, Boston, MA, United States. 10. Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, United States; James J. Peters VA Medical Center, New York, NY, United States. 11. Department of Psychiatry and Biobehavioral Science, Geffen School of Medicine, University of California Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States; Department of Biostatistics, University of California Los Angeles, CA, United States. 12. Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Institute for Genomic Medicine, University of California, San Diego, CA, United States; Harvard Institute of Psychiatry Epidemiology and Genetics, Boston, MA, United States.
Abstract
OBJECTIVES: Working memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia. METHODS: From 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the letter-number span (LNS) task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the forward condition, participants repeated the letters and numbers in the order they were presented. In the reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order. RESULTS: Schizophrenia patients performed more poorly than controls, with a larger difference on reorder than forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment. CONCLUSIONS: Results confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke.
OBJECTIVES:Working memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia. METHODS: From 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the letter-number span (LNS) task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the forward condition, participants repeated the letters and numbers in the order they were presented. In the reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order. RESULTS:Schizophreniapatients performed more poorly than controls, with a larger difference on reorder than forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment. CONCLUSIONS: Results confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke.
Authors: Sarah M Hartz; Carlos N Pato; Helena Medeiros; Patricia Cavazos-Rehg; Janet L Sobell; James A Knowles; Laura J Bierut; Michele T Pato Journal: JAMA Psychiatry Date: 2014-03 Impact factor: 21.596
Authors: Kristi A Sacco; Angelo Termine; Aisha Seyal; Melissa M Dudas; Jennifer C Vessicchio; Suchitra Krishnan-Sarin; Peter I Jatlow; Bruce E Wexler; Tony P George Journal: Arch Gen Psychiatry Date: 2005-06
Authors: Keith H Nuechterlein; Deanna M Barch; James M Gold; Terry E Goldberg; Michael F Green; Robert K Heaton Journal: Schizophr Res Date: 2004-12-15 Impact factor: 4.939
Authors: Ruth S Barr; Melissa A Culhane; Lindsay E Jubelt; Rana S Mufti; Michael A Dyer; Anthony P Weiss; Thilo Deckersbach; John F Kelly; Oliver Freudenreich; Donald C Goff; A Eden Evins Journal: Neuropsychopharmacology Date: 2007-04-18 Impact factor: 7.853
Authors: Stanley Zammit; Peter Allebeck; Christina Dalman; Ingvar Lundberg; Tomas Hemmingsson; Glyn Lewis Journal: Am J Psychiatry Date: 2003-12 Impact factor: 18.112
Authors: Michael L Thomas; Virginie M Patt; Andrew Bismark; Joyce Sprock; Melissa Tarasenko; Gregory A Light; Gregory G Brown Journal: J Abnorm Psychol Date: 2017-03-09
Authors: Keith H Nuechterlein; Michael F Green; Monica E Calkins; Tiffany A Greenwood; Raquel E Gur; Ruben C Gur; 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; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; David L Braff Journal: Schizophr Res Date: 2015-03-04 Impact factor: 4.939
Authors: Gabriëlla A M Blokland; Raquelle I Mesholam-Gately; Timothea Toulopoulou; Elisabetta C Del Re; Max Lam; Lynn E DeLisi; Gary Donohoe; James T R Walters; Larry J Seidman; Tracey L Petryshen Journal: Schizophr Bull Date: 2017-07-01 Impact factor: 9.306
Authors: Ruben C Gur; David L Braff; Monica E Calkins; Dorcas J Dobie; Robert Freedman; Michael F Green; Tiffany A Greenwood; Laura C Lazzeroni; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Larry J Seidman; Larry J Siever; Jeremy M Silverman; Joyce Sprock; William S Stone; Catherine A Sugar; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Raquel E Gur Journal: Schizophr Res Date: 2015-04 Impact factor: 4.939
Authors: Melissa Tarasenko; Veronica B Perez; Sean T Pianka; Sophia Vinogradov; David L Braff; Neal R Swerdlow; Gregory A Light Journal: Schizophr Res Date: 2016-02-02 Impact factor: 4.939
Authors: Tiffany A Greenwood; Laura C Lazzeroni; Adam X Maihofer; Neal R Swerdlow; Monica E Calkins; Robert Freedman; Michael F Green; Gregory A Light; Caroline M Nievergelt; Keith H Nuechterlein; Allen D Radant; Larry J Siever; Jeremy M Silverman; William S Stone; Catherine A Sugar; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Ruben C Gur; Raquel E Gur; David L Braff Journal: JAMA Psychiatry Date: 2019-12-01 Impact factor: 21.596
Authors: William S Stone; Raquelle I Mesholam-Gately; David L Braff; Monica E Calkins; Robert Freedman; Michael F Green; Tiffany A Greenwood; Raquel E Gur; Ruben C Gur; Laura C Lazzeroni; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Larry J Siever; Jeremy M Silverman; Joyce Sprock; Catherine A Sugar; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Larry J Seidman Journal: Schizophr Res Date: 2014-12-12 Impact factor: 4.939