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

SCHIZOPHRENIA RESEARCH

卷:198

Article

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

[1] Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA

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

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

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

[5] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA

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

[7] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[8] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[9] VA San Diego Healthcare Syst, VISN 22, MIRECC, San Diego, CA USA

[10] Harvard Med Sch, Dept Psychiat, Boston, MA USA

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

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

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

[14] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 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: Endophenotype;    Prepulse inhibition;    Replication;    Schizophrenia;    Startle;   

DOI  :  10.1016/j.schres.2017.05.013

来源: Elsevier

【 摘 要 】

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) defidts 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 Wl; 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 < 0.0004). Strict response criteria excluded almost 39% of all subjects, disproportionately impacting specific subgroups: ANOVA in this smaller cohort confirmed no significant effect of wave or wave x diagnosis interaction, and a significant effect of diagnosis (p < 0.002). Antipsychotic-free, early-illness patients had particularly robust PPI deficits. Discussion: Schizophrenia-linked PPI deficits were replicable across two multi-site waves of subjects collected over 3.5 years. Strict response criteria disproportionately excluded older, male, non-Caucasian patients with low-normal hearing acuity. These findings set the stage for genetic analyses of PPI using the combined COGS wave 1 and 2 cohorts. (C) 2017 Elsevier B.V. All rights reserved.

【 授权许可】

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