Skip to main content
SpringerLink
Log in

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Prepulse Inhibition (PPI) of startle is an operational measure of the pre-attentive filtering process known as sensorimotor gating. Originally identified in patients with schizophrenia, PPI deficits have been observed in multiple but not all psychiatric disorders. Thus, as with most signs and symptoms of psychiatric disorders, deficits in PPI cut across diagnostic categories. It remains unclear whether the diversity of disorders exhibiting deficient PPI bespeaks diagnostic overlaps or comorbidities. Given the recent focus on treatments for cognitive deficits of schizophrenia independently of treating psychosis, the relationship of PPI deficits to cognitive deficits becomes of interest. Although PPI cannot be considered to be a cognitive process per se, abnormalities in pre-attentive information processing may be predictive of or lead to complex cognitive deficits. Animal models of PPI deficits produced by dopamine agonists reliably predict existing antipsychotics. Nevertheless, since neither PPI nor cognitive deficits in schizophrenia are ameliorated by standard antipsy-chotics, current research is exploring the predictive value of non-dopaminergic PPI models in identifying treatments for gating disturbances independently of their relevance to specific disorders. Both PPI and cognitive deficits in schizophrenia patients are not reversed by first generation antipsychotics but may be attenuated by clozapine. Similarly, effects of glutamate antagonists on symptoms in patients and PPI in animals appear to be reduced by clozapine. Hence, treatment-induced reversals of deficits in PPI produced by glutamate antagonists may provide animal, and human, models to aid in the discovery of treatments of cognitive deficits in patients already treated with existing antipsychotics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abduljawad KA, RW Langley, CM Bradshaw and E Szabadi (1999) Effects of bromocriptine and haloperidol on prepulse inhibition: comparison of the acoustic startle eyeblink response and the N1/P2 auditory-evoked response in man.J. Psychopharmacology 13, 3–9.

    Article  CAS  Google Scholar 

  • Bakshi VP and MA Geyer (1998) Multiple limbic regions mediate the disruption of prepulse inhibition produced in rats by the noncompetitive NMDA antagonist, dizocilpine.J. Neurosci. 18, 8394–8401.

    PubMed  CAS  Google Scholar 

  • Braff DL and MA Geyer (1990) Sensorimotor gating and schizophrenia: human and animal model studies.Arch. Gen. Psychiatry 47, 181–188.

    PubMed  CAS  Google Scholar 

  • BraffD, C Stone, E Callaway, M Geyer, I Glick and L Bali (1978) Prestimulus effects on human startle reflex in normals and schizophrenics.Psychophysiology 15, 339–343.

    Article  PubMed  CAS  Google Scholar 

  • Braff DL, MA Geyer and NR Swerdlow (2001) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.Psychopharmacology 156, 234–258.

    Article  PubMed  CAS  Google Scholar 

  • Brody SA, F Conquet and MA Geyer (2004) Effect of antipsychotic treatment on the prepulse inhibition deficit of mgluR5 knockout mice.Psychopharmacology 172, 187–195.

    Article  PubMed  CAS  Google Scholar 

  • Buchanan RW, M Davis, D Goffet al. (2005) A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia.Schizophr. Bull. 31, 5–19.

    Article  PubMed  Google Scholar 

  • CiliaJ, PD Hatcher, C Reavill and DNC Jones (2005) Longterm evaluation of isolation-rearing induced prepulse inhibition deficits in rats: an update. Psychopharmacology180, 57–62.

    Article  PubMed  CAS  Google Scholar 

  • Fenton WS, EL Stover and TR Insel (2003) Breaking the logjam in treatment development for cognition in schizophrenia.Psychopharmacology 169, 365–366.

    Article  PubMed  CAS  Google Scholar 

  • FlorescoS, MA Geyer, LH Gold and A Grace (2005) Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia.Schizophr. Bull. 31, 888–894.

    Article  PubMed  Google Scholar 

  • Frankland PW, Y Wang, B Rosner, T Shimizu, BW Balleine, EM Dykens, EM Ornitz and AJ Silva (2004) Sensorimotor gating abnormalities in young males with Fragile X syndrome and Fmrl-knockout mice.Mol Psychiatry 9, 417–425.

    Article  PubMed  CAS  Google Scholar 

  • FreedmanR, LE Adler and S Leonard (1999) Alternative phenotypes for the complex genetics of schizophrenia.Biol. Psychiatry 45, 551–558.

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA and DL Braff (1987) Startle habituation and sensorimotor gating in schizophrenia and related animal models.Schizophr. Bull. 13, 643–668.

    PubMed  CAS  Google Scholar 

  • Geyer MA and BA Ellenbroek (2003) Animal behavior models of the mechanisms underlying antipsychotic atypicality.Prog. Neuropsychopharmacol Biol Psychiatry 27, 1071–1079.

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA and R Heinssen (2005) New approaches to measurement and treatment research to improve cognition in schizophrenia (MATRICS).Schizophr. Bull. 31, 806–809.

    Article  PubMed  Google Scholar 

  • Geyer MA and A Markou (2002) The role of preclinical models in the development of psychotropic drugs, In:Neuropsychopharm-acology: The Fifth Generation of Progress (Davis KL, D Charney, J.T. Coyle and C Nemeroff, Eds.) (Lippincott Williams and Wilkins:Philadelphia, PA), pp 445–455.

    Google Scholar 

  • Geyer MA and B Moghaddam (2002) Animal models relevant to schizophrenia disorders, In:Neuropsychopharmacology: The Fifth Generation of Progress (Davis KL, D Charney, J.T. Coyle and C Nemeroff, Eds.) (Lippincott Williams and Wilkins:Philadelphia, PA), pp 689–701.

    Google Scholar 

  • Geyer MA and CA Tamminga (2004) Measurement and treatment research to improve cognition in schizophrenia: neuropharmacological aspects.Psychopharmacology 174, 1–2.

    Article  CAS  Google Scholar 

  • Geyer MA, NR Swerdlow, RS Mansbach and DL Braff (1990) Startle response models of sensorimotor gating and habituation deficits in schizophrenia.Brain Res. Bull. 25, 485–498.

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA, K Krebs-Thomson, DL Braff and NR Swerdlow (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.Psychopharmacology 156, 117–154.

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA, KL Mcllwain and R Paylor (2002) Mouse genetic models for prepulse inhibition: an early review.Mol. Psychiatry 7, 1039–1053.

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS, SA Castner, TH Svensson, LJ Siever and GV Williams (2004) Targeting the dopamineD 1 receptor in schizophrenia: insights for cognitive dysfunction.Psychopharmacology 174, 3–16.

    Article  PubMed  CAS  Google Scholar 

  • Graham FK (1975) The more or less startling effects of weak prestimuli.Psychophysiology 12, 238–248.

    Article  PubMed  CAS  Google Scholar 

  • Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia?Am. J. Psych. 153, 321–330.

    CAS  Google Scholar 

  • Green MF, SR Kerns and RK Heaton (2004a) Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS.Schizophr. Res. 72, 45–51.

    Google Scholar 

  • Green MF, KH Nuechterlein, JM Goldet al. (2004b) Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria.Biol. Psychiatry 56, 301–307.

    Article  PubMed  Google Scholar 

  • Hagan JJ and DN Jones (2005) Predicting drug efficacy for cognitive deficits in schizophrenia.Schizophr. Bull. 31, 830–853

    Article  PubMed  Google Scholar 

  • Hawk LW, AR Yartz, WE Pelham. and TM Lock (2003) The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attentiondeficit hyperactivity disorder.Psychopharmacology 165, 118–127.

    PubMed  CAS  Google Scholar 

  • HejlA, B Glenthøj, T Mackeprang, R Hemmingsen and G Waldemar (2004) Prepulse inhibition in patients with Alzheimer’s disease.Neurobiol. Aging 25, 1045–1050.

    Article  PubMed  CAS  Google Scholar 

  • HoenigK, A Hochrein, BB Quednow, W Maier and M Wagner (2005) Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder.Biol. Psychiatry 57, 1153–1158.

    Article  PubMed  Google Scholar 

  • Hyman SE and WS Fenton (2003) What are the right targets for psychopharmacology?Science 299, 350–351.

    Article  PubMed  CAS  Google Scholar 

  • Karper LP, GK Freeman, C Grillon, CA Morgan 3rd, DS Charney and JH Krystal (1996) Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis.J. Neuropsychiatry Clin. Neurosci. 8, 60–66.

    PubMed  CAS  Google Scholar 

  • Krystal JH, LP Karper, JP Seibyl, GK Freeman, R Delaney, JD Bremner, GR Heninger, MB Bowers Jr and DS Charney (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans.Arch. Gen. Psychiatry 51, 199–214.

    PubMed  CAS  Google Scholar 

  • KumariV and T Sharma (2002) Effects of typical and atypical antipsychotics on prepulse inhibition in schizophrenia: a critical evaluation of current evidence and directions for future research.Psychopharmacology 162, 97–101.

    Article  PubMed  CAS  Google Scholar 

  • KumariV, W Soni and T Sharma (1999) Normalization of information processing deficits in schizophrenia with clozapine.Am. J. Psychiatry 156, 1046–1051.

    PubMed  CAS  Google Scholar 

  • Linn GS, SS Negi, SV Gerum and DC Javitt (2003) Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys.Psychopharmacology 169, 234–239.

    Article  PubMed  CAS  Google Scholar 

  • LudewigS and K Ludewig (2003) No prepulse inhibition deficits in patients with unipolar depression.Depress. Anxiety 17, 224–225.

    Article  PubMed  Google Scholar 

  • LudewigS, K Ludewig, MA Geyer, D Hell and FX Vollenweider (2002) Prepulse inhibition deficits in patients with panic disorder.Depress. Anxiety 15, 55–60.

    Article  PubMed  CAS  Google Scholar 

  • LudewigK, MA Geyer and FX Vollenweider (2003) Deficits in prepulse inhibition and habituation in never-medicated first-episode schizophrenia.Biol. Psychiatry 54, 121–128.

    Article  PubMed  Google Scholar 

  • LudewigS, MA Geyer, M Ramseier, FX Vollenweider, E Rechsteiner and K Ludewig (2005) Information processing deficits and cognitive dysfunctions in panic disorder.J. Psychiatr. Neurosci. 30, 37–43.

    Google Scholar 

  • Malhotra AK, DA Finals, H Weingartner, K Sirocco, CD Missar, D Pickar and A Breier (1996) NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers.Neuropsychopharmacology 14, 301–307.

    Article  PubMed  CAS  Google Scholar 

  • Malhotra AK, CM Adler, SD Kennison, I Elman, D Pickar and A Breier (1997a) Clozapine blunts JV-methyl-D-aspartate antagonist-induced psychosis: a study with ketamine.Biol. Psychiatry 42, 664–668.

    Article  PubMed  CAS  Google Scholar 

  • Malhotra AK, DA Finals, CM Adler, I Elman, A Clifton, D Pickar and A Breier (1997b) Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics.Neuropsychopharmacology 17, 141–150.

    Article  PubMed  CAS  Google Scholar 

  • Marder SR and W Fenton (2004) Measurement and Treatment Research to Improve Cognition in Schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia.Schizophr. Res. 72, 5–9.

    Article  PubMed  Google Scholar 

  • Martin LF, WR Kem and R Freedman (2004) Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia.Psychopharmacology 174, 54–64.

    Article  PubMed  CAS  Google Scholar 

  • McAlonan GM, E Daly, V Kumari, HD Critchley, T van Amelsvoort, J Suckling, A Simmons, T Sigmundsson, K Greenwood, A Russell, N Schmitz, F Happe, P Howlin and DG Murphy (2002) Brain anatomy and sensorimotor gating in Asperger’s syndrome.Brain 125 (part 7), 1594–1606.

    Article  PubMed  Google Scholar 

  • MeinckeU, D Mörth, T Voss, B Thelen, MA Geyer and E Gouzoulis-Mayfrank (2004) Prepulse inhibition of the acoustically evoked startle reflex in patients with an acute schizophrenic psychosis - a longitudinal study.Eur. Arch. Psychiatr Clin. Neurosci. 254, 415–421.

    Article  Google Scholar 

  • Meltzer HY and SR McGurk (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.Schizophr. Bull. 25, 233–255.

    PubMed  CAS  Google Scholar 

  • Nuechterlein KH, DM Barch, JM Gold, TE Goldberg, MF Green and RK Heaton (2004) Identification of separable cognitive factors in schizophrenia.Schizophr. Res. 72, 29–39.

    Article  PubMed  Google Scholar 

  • PenG and JL Moreau (2002). Disruption of prepulse inhibition of startle reflex in a neurodevelopmental model of schizophrenia: reversal by clozapine, olanzapine and risperidone but not by haloperidol.Neuropsychopharmacology 27, 1–11.

    Article  PubMed  Google Scholar 

  • Perriol M-P, K Dujardin, P Derambure, A Marcq, J-L Bourriez, E Laureau, F Pasquier, L Defebvre and A Deste’e (2005) Disturbance of sensory filtering in dementia with Lewy bodies comparison with Parkinson’s disease dementia and Alzheimer’s disease.J. Neurol. Neurosurg. Psychiatry 76, 106–108.

    Article  PubMed  Google Scholar 

  • PerryW, MA Geyer and DL Braff (1999) Sensorimotor gating and thought disturbance measured in close temporal proximity in schizophrenic patients.Arch. Gen. Psychiatry 56, 227–281.

    Article  Google Scholar 

  • PerryW, A Minassian, D Feifel and DL Braff (2001) Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania.Biol Psychiatry 50, 418–424.

    Article  PubMed  CAS  Google Scholar 

  • PerryW, A Minassian and D Feifel (2004) Prepulse inhibition in patients with non-psychotic major depressive disorder.J. Affect. Disord. 81, 179–184.

    Article  PubMed  Google Scholar 

  • Pouretemad HR, PJ Thompson and BC Fenwick (1998) Impaired sensorimotor gating in patients with non-epileptic seizures.Epilepsy Res. 31, 1–12.

    Article  PubMed  CAS  Google Scholar 

  • Powell SB and MA Geyer (2002) Developmental markers of psychiatric disorders as identified by sensorimotor gating.Neurotoxicity Res. 4, 489–502.

    Article  Google Scholar 

  • Quednow BB, KU Kuhn, R Stelzenmueller, K Hoenig, W Maier and M Wagner (2004) Effects of serotonergic and noradrenergic antidepressants on auditory startle response in patients with major depression.Psychopharmacology 175, 399–406.

    PubMed  CAS  Google Scholar 

  • Ralph RJ and SB Caine (2005) Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague-Dawley rats to Swiss-Webster, 129Xl/SvJ, C57BL/6J, and DBA/2J Mice.J. Pharmacol. Exp. Ther. 312, 733–741.

    Article  PubMed  CAS  Google Scholar 

  • Ralph RJ, GB Varty, MA Kelly, Y-M Wang, MG Caron, M Rubinstein, DK Grandy, MJ Low and MA Geyer (1999) The dopamine D2 but not D3 or D4 receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice.J. Neurosci. 19, 4627–4633.

    PubMed  CAS  Google Scholar 

  • Ralph RJ, MP Paulus, F Fumagalli, MG Caron and MA Geyer (2001) Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knockout mice: differential effects of D1 and D2 receptor antagonists.J. Neurosci. 21, 305–313.

    PubMed  CAS  Google Scholar 

  • Ralph-Williams RJ, V Lehmann-Masten, V Otero-Corchon, MJ Low and MA Geyer (2002) Differential effects of direct and indirect dopamine agonists on prepulse inhibition: a study in D1 and D2 receptor knockout mice.J. Neurosci. 22, 9604–9611.

    PubMed  CAS  Google Scholar 

  • Ralph-Williams RJ, V Lehmann-Masten and MA Geyer (2003) Dopamine D1 rather than D2 receptor agonists disrupt prepulse inhibition of startle in mice.Neuropsychopharmacology 28, 108–118.

    Article  PubMed  CAS  Google Scholar 

  • Rich BA, D Vinton, C Grillon, RK Bhangoo and E Leibenluft (2005) An investigation of prepulse inhibition in pediatric bipolar disorder.Bipolar Disord. 7, 198–203.

    Article  PubMed  Google Scholar 

  • SobinC, K Kiley-Brabeck and M Karayiorgou (2005) Lower prepulse inhibition in children with the 22q11 deletion syndrome.Am. J. Psychiatry 162, 1090–1099.

    Article  PubMed  Google Scholar 

  • Swerdlow NR, DL Braff, N Taaid and MA Geyer (1994) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients.Arch. Gen. Psychiatry 51, 139–154.

    PubMed  CAS  Google Scholar 

  • Swerdlow NR, ZA Martinez, F Hanlon, A Platten, M Farid, P Auerbach, DL Braff and MA Geyer (2000) Towards understanding the biology of a complex phenotype: rat strain and substrain differences in the sensorimotor gating-disruptive effects of dopamine agonists.J. Neurosci. 20, 4325–4336.

    PubMed  CAS  Google Scholar 

  • Swerdlow NR, MA Geyer and DL Braff (2001) Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges.Psychopharmacology 156, 194–215.

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, A Eastvold, B Karban, Y Ploum, N Stephany, MA Geyer, KS Cadenhead and PP Auerbach (2002) Dopamine agonist effects on startle and sensorimotor gating in normal control subjects: time course studies.Psychopharmacology 161, 189–201.

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, AS Krupin, MJ Bongiovanni, JM Shoemaker, JC Goins and RP Hammer (2006) Heritable differences in the dopaminergic regulation of behavior in rats: relationship to D2-like receptor G-protein function.Neuropsychopharmacology doi: 10.1038/sj.npp. 1300877

  • Vollenweider FX and MA Geyer (2001) A systems model of altered consciousness: integrating natural and drug-induced psychoses.Brain Res. Bull. 56, 495–507.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of California San Diego, 9500 Gilman Drive #0804, CA 92093-0804, La Jolla, USA

    Mark A. Geyer

Authors
  1. Mark A. Geyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark A. Geyer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Geyer, M.A. The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?. neurotox res 10, 211–220 (2006). https://doi.org/10.1007/BF03033358

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033358

Keywords

Search

Navigation