Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

SCHIZOPHRENIA RESEARCH

卷:152

Review

Swerdlow, Neal R.¹  Light, Gregory A.^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  Ray, Amrita^7,8  Seidman, Larry J.^10,11  Siever, Larry J.^12,13  Silverman, Jeremy M.^12,13  Stone, William S.^10,11  Sugar, Catherine A.^5,9,14  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, 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, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 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, MIRECC, VISN 22, San Diego, CA USA

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

[11] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, 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;    Genetics;    Multi-site;    Prepulse inhibition;    Schizophrenia;    Startle;   

DOI  :  10.1016/j.schres.2013.12.004

来源: Elsevier

【 摘 要 】

Background: Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site COGS-2 study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data. Methods: Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n = 1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures. Results: 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p = 0.0005) and sex (p < 0.002), and a significant diagnosis x test site interaction. HCS > schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures. Discussion: The COGS-2multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia endophenotype of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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