Prepulse Inhibition of the Startle Reflex: A Window on the Brain in Schizophrenia

Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 4)

Abstract

Prepulse inhibition (PPI) of the startle response is an important measure of information processing deficits and inhibitory failure in schizophrenia patients. PPI is especially useful because it occurs in the same lawful manner in all mammals, from humans to rodents, making it an ideal candidate for cross-species translational research. PPI deficits occur across the “schizophrenia spectrum” from schizophrenia patients to their clinically unaffected relatives. Parallel animal model and human brain imaging studies have demonstrated that PPI is modulated by cortico-striato-pallido-thalamic (and pontine) circuitry. This circuitry is also implicated in schizophrenia neuropathology and neurophysiology. The finding of PPI deficits in schizophrenia patients has been replicated by many groups, and these deficits correlate with measures of thought disorder and appear to be “normalized” by second generation antipsychotic (SGA) medications. Consistent pharmacological effects on PPI have been demonstrated; among these, dopamine agonists induce PPI deficits and (in animal models) these are reversed by first and SGA medications. PPI is also significantly heritable in humans and animals and can be used as a powerful endophenotype in studies of families of schizophrenia patients. Genomic regions, including the NRGL-ERBB4 complex with its glutamatergic influences, are strongly implicated in PPI deficits in schizophrenia. PPI continues to hold promise as an exciting translational cross-species measure that can be used to understand the pathophysiology and treatment of the schizophrenias via pharmacological, anatomic, and genetic studies.

Keywords

Schizophrenia Prepulse inhibition Information processing Endophenotype Animal models Dopamine 

Notes

Acknowledgments

This work was supported in part by grants from the National Institute of Mental Health (MH42228, MH065571), a NARSAD Distinguished Investigator Award and the Department of Veteran Affairs, VISN 22 MIRECC (Mental Illness Research, Education, and Clinical Center) on Schizophrenia and Psychosis. The author thanks his colleagues Neal Swerdlow and Mark Geyer who authored two of the three cited 2001 Psychopharmacology review papers. This chapter is an update and extension of Braff et al. (2001). The author also would like to thank Dr. Swerdlow for his very helpful comments on this manuscript.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of California, San Diego (UCSD)La JollaUSA

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