Factor structure and heritability of endophenotypes in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1)

SCHIZOPHRENIA RESEARCH

卷:163

Article

Seidman, Larry J.^1,2  Hellemann, Gerhard³  Nuechterlein, Keith H.^3,4  Greenwood, Tiffany A.⁵  Braff, David L.^5,6  Cadenhead, Kristin S.⁵  Calkins, Monica E.⁷  Freedman, Robert⁸  Gur, Raquel E.⁷  Gur, Ruben C.⁷  Lazzeroni, Laura C.⁹  Light, Gregory A.⁶  Olincy, Ann⁸  Radant, Allen D.^10,11  Siever, Larry J.^12,13  Silverman, Jeremy M.¹²  Sprock, Joyce⁵  Stone, William S.^1,2  Sugar, Catherine^3,14,15  Swerdlowe, Neal R.⁵  Tsuang, Debby W.^10,11  Tsuang, Ming T.^2,5,16,17  Turetsky, Bruce I.⁷  Green, Michael F.^3,15 

[1] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Dept Psychiat, Boston, MA 02115 USA

[2] Harvard Inst Psychiat Epidemiol & Genet s, Boston, MA USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA

[5] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[6] Mental Illness Res Educ & Clin Ctr MIRE, VA San Diego Healthcare Syst VISN 22, San Diego, CA USA

[7] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA

[8] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA

[9] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[10] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[11] Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs VISN 20, Seattle, WA USA

[12] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA

[13] Mental Illness Res Educ & Clin Ctr, James J Peters VA & VISN3, Bronx, NY USA

[14] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA

[15] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA

[16] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA

[17] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

关键词: Schizophrenia;    Endophenotype;    Neurocognition;    Neurophysiology;    Genetics;   

DOI  :  10.1016/j.schres.2015.01.027

来源: Elsevier

【 摘 要 】

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. (C) 2015 Elsevier B.V. All rights reserved.

【 授权许可】

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