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

  • Author(s): Swerdlow, Neal R
  • Light, Gregory A
  • Thomas, Michael L
  • Sprock, Joyce
  • Calkins, Monica E
  • Green, Michael F
  • Greenwood, Tiffany A
  • Gur, Raquel E
  • Gur, Ruben C
  • Lazzeroni, Laura C
  • Nuechterlein, Keith H
  • Radant, Allen D
  • Seidman, Larry J
  • Siever, Larry J
  • Silverman, Jeremy M
  • Stone, William S
  • Sugar, Catherine A
  • Tsuang, Debby W
  • Tsuang, Ming T
  • Turetsky, Bruce I
  • Braff, David L
  • et al.
Abstract

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) deficits 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 W1; 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 3.5years. 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.

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