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Schizophr Res. 2018 Aug;198:6-15. doi: 10.1016/j.schres.2017.05.013. Epub 2017 May 24.

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

Author information

1
Department of Psychiatry, University of California San Diego, La Jolla, CA, United States. Electronic address: nswerdlow@ucsd.edu.
2
Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VISN 22, Mental Illness Research, Education & Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA.
3
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
4
Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
5
Department of Psychiatry, University of California San Diego, La Jolla, CA, United States.
6
Departments of Psychiatry and Behavioral Sciences and of Pediatrics, Stanford University, Stanford, CA, United States.
7
Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States.
8
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States; VA Puget Sound Health Care System, Seattle, WA, United States.
9
Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA, United States.
10
Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, United States; James J. Peters VA Medical Center, New York, NY, United States.
11
Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States; VISN 22, Mental Illness Research, Education & Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA; Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, CA, United States.
12
Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, United States; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA, United States.

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.

KEYWORDS:

Endophenotype; Prepulse inhibition; Replication; Schizophrenia; Startle

PMID:
28549722
PMCID:
PMC5700873
[Available on 2019-08-01]
DOI:
10.1016/j.schres.2017.05.013

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