The utility of P300 as a schizophrenia endophenotype and predictive biomarker: Clinical and socio-demographic modulators in COGS-2

SCHIZOPHRENIA RESEARCH

卷:163

Article

Turetsky, Bruce I.¹  Dress, Erich M.¹  Braff, David L.^2,3  Calkins, Monica E.¹  Green, Michael F.^4,5  Greenwood, Tiffany A.²  Gur, Raquel E.¹  Gur, Ruben C.¹  Lazzeroni, Laura C.⁶  Nuechterlein, Keith H.⁴  Radant, Allen D.^7,8  Seidman, Larry J.^9,10  Siever, Larry J.^11,12  Silverman, Jeremy M.^11,12  Sprock, Joyce²  Stone, William S.^9,10  Sugar, Catherine A.¹³  Tsuang, Debby W.^7,8  Tsuang, Ming T.^2,14,15,16  Light, Gregory^2,3 

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

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

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

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

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

[6] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA

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

[8] VA Puget Sound Hlth Care Syst, Seattle, WA USA

[9] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA

[10] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA

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

[12] James J Peters VA Med Ctr, New York, NY USA

[13] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA

[14] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA

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

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

关键词: P300;    Schizophrenia;    Endophenotype;    Biomarker;    Event-related potential;   

DOI  :  10.1016/j.schres.2014.09.024

来源: Elsevier

【 摘 要 】

Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 controls and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

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