Multi-site studies of acoustic startle and prepulse inhibition in humans: initial experience and methodological considerations based on studies by the Consortium on the Genetics of Schizophrenia.
BACKGROUND
Startle and its inhibition by weak lead stimuli ("prepulse inhibition": PPI) are studied to understand the neurobiology of information processing in patients and community comparison subjects (CCS). PPI has a strong genetic basis in infrahumans, and there is evidence for its heritability, stability and reliability in humans. PPI has gained increasing use as an endophenotype to identify vulnerability genes for brain disorders, including schizophrenia. Genetic studies now often employ multiple, geographically dispersed test sites to accommodate the need for large and complex study samples. Here, we assessed the feasibility of using PPI in multi-site studies.


METHODS
Within a 7-site investigation with multiple measures, the Consortium on the Genetics of Schizophrenia conducted a methodological study of acoustic startle and PPI in CCS. Methods were manualized, videotaped and standardized across sites with intensive in-person training sessions. Equipment was acquired and programmed at the "PPI site" (UCSD), and stringent quality assurance (QA) procedures were used. Testing was completed on 196 CCS over 2.5 years, with 5 primary startle dependent measures: eyeblink startle magnitude, habituation, peak latency, latency facilitation and PPI.


RESULTS
Analyses identified significant variability across sites in some but not all primary measures, and determined factors both within the testing process and subject characteristics that influenced a number of test measures. QA procedures also identified non-standardized practices with respect to testing methods and procedural "drift", which may be particularly relevant to multi-site studies using these measures.


CONCLUSIONS
With thorough oversight and QA procedures, measures of acoustic startle PPI can be acquired reliably across multiple testing sites. Nonetheless, even among sites with substantial expertise in utilizing psychophysiological measures, multi-site studies using startle and PPI as dependent measures require careful attention to methodological procedures.
Swerdlow
Neal R
NR
Department of Psychiatry, University of California San Diego, San Diego, California, USA. nswerdlow@ucsd.edu
Sprock
Joyce
J
Light
Gregory A
GA
Cadenhead
Kristin
K
Calkins
Monica E
ME
Dobie
Dorcas J
DJ
Freedman
Robert
R
Green
Michael F
MF
Greenwood
Tiffany A
TA
Gur
Raquel E
RE
Mintz
Jim
J
Olincy
Ann
A
Nuechterlein
Keith H
KH
Radant
Allen D
AD
Schork
Nicholas J
NJ
Seidman
Larry J
LJ
Siever
Larry J
LJ
Silverman
Jeremy M
JM
Stone
William S
WS
Tsuang
Debbie W
DW
Tsuang
Ming T
MT
Turetsky
Bruce I
BI
Braff
David L
DL
D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D032921:Consensus; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008606:Mental Processes; D008875:Middle Aged; D009483:Neuropsychological Tests; D011584:Psychology / Q000379:methods*; D013216:Reflex, Startle / Q000502:physiology*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D012720:Severity of Illness Index