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

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.