title: Factor structure and heritability of endophenotypes in schizophrenia: findings from the Consortium on the Genetics of Schizophrenia (COGS-1).
abstract: BACKGROUND
  Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements.
  
  
  METHODS
  The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR.
  
  
  RESULTS
  Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction).
  
  
  CONCLUSIONS
  Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia.
authors: Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, Boston, MA, United States; Harvard Institute of Psychiatric Epidemiology and Genetic s, Boston, MA, United States. Electronic address: lseidman@bidmc.harvard.edu.
authors: Larry J
authors: LJ
authors: Seidman
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States.
authors: Gerhard
authors: G
authors: Hellemann
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States; Department of Psychology, University of California Los Angeles, Los Angeles, CA, United States.
authors: Keith H
authors: KH
authors: Nuechterlein
authors: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States.
authors: Tiffany A
authors: TA
authors: Greenwood
authors: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VA San Diego Healthcare System VISN-22 Mental Illness Research, Education, and Clinical Center (MIRECC), San Diego, CA, United States. Electronic address: dbraff@ucsd.edu.
authors: David L
authors: DL
authors: Braff
authors: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States.
authors: Kristin S
authors: KS
authors: Cadenhead
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors: Monica E
authors: ME
authors: Calkins
authors: Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, United States.
authors: Robert
authors: R
authors: Freedman
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors: Raquel E
authors: RE
authors: Gur
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors: Ruben C
authors: RC
authors: Gur
authors: Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA, United States.
authors: Laura C
authors: LC
authors: Lazzeroni
authors: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VA San Diego Healthcare System VISN-22 Mental Illness Research, Education, and Clinical Center (MIRECC), San Diego, CA, United States.
authors: Gregory A
authors: GA
authors: Light
authors: Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, United States.
authors: Ann
authors: A
authors: Olincy
authors: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States; The Department of Veteran Affairs VISN-20 Mental Illness Research, Education, and Clinical Center, Seattle, WA, United States.
authors: Allen D
authors: AD
authors: Radant
authors: Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, United States; James J. Peters VA & VISN3 Mental Illness Research, Education and Clinical Center, Bronx, NY, United States.
authors: Larry J
authors: LJ
authors: Siever
authors: Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, United States.
authors: Jeremy M
authors: JM
authors: Silverman
authors: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States.
authors: Joyce
authors: J
authors: Sprock
authors: Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, Boston, MA, United States; Harvard Institute of Psychiatric Epidemiology and Genetic s, Boston, MA, United States.
authors: William S
authors: WS
authors: Stone
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States; Department of Biostatistics, University of California Los Angeles, Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
authors: Catherine
authors: C
authors: Sugar
authors: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States.
authors: Neal R
authors: NR
authors: Swerdlow
authors: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States; The Department of Veteran Affairs VISN-20 Mental Illness Research, Education, and Clinical Center, Seattle, WA, United States.
authors: Debby W
authors: DW
authors: Tsuang
authors: Harvard Institute of Psychiatric Epidemiology and Genetic s, Boston, MA, United States; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Center for Behavioral Genomics, Department of Psychiatry and Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, United States.
authors: Ming T
authors: MT
authors: Tsuang
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors: Bruce I
authors: BI
authors: Turetsky
authors: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
authors: Michael F
authors: MF
authors: Green
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001143:Arousal / Q000235:genetics; D058068:Endophenotypes; D005163:Factor Analysis, Statistical; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D061212:Memory, Episodic; D008570:Memory, Short-Term; D008875:Middle Aged; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D035781:Siblings; D014796:Visual Perception / Q000235:genetics; D055815:Young Adult
keywords: Endophenotype; Genetics; Neurocognition; Neurophysiology; Schizophrenia