Hostname: page-component-7c8c6479df-p566r Total loading time: 0 Render date: 2024-03-28T12:18:59.330Z Has data issue: false hasContentIssue false

Prepulse inhibition and “psychosis-proneness” in healthy individuals: An fMRI study

Published online by Cambridge University Press:  16 April 2020

Veena Kumari*
Affiliation:
Department of Psychology, P078, Institute of Psychiatry, King's College London, De Crespigny Park, LondonSE5 8AF, UK
Elena Antonova
Affiliation:
Department of Psychology, P078, Institute of Psychiatry, King's College London, De Crespigny Park, LondonSE5 8AF, UK
Mark A. Geyer
Affiliation:
Department of Psychiatry, University of California, CA, USA
*
Corresponding author. Tel.: +44 207 848 0233; fax: +44 207 848 0860. E-mail address: v.kumari@iop.kcl.ac.uk (V. Kumari).
Get access

Abstract

Objective

Prepulse inhibition (PPI) of the startle response provides an operational index of sensorimotor gating that is reliably demonstrable in both human and animal subjects. Patients with schizophrenia, first-degree relatives of patients with schizophrenia, patients with schizotypal personality disorder and healthy individuals scoring high on psychometric measures of psychosis-proneness display reduced PPI. This study examined associations between individual differences in “psychosis-proneness” and brain activity during a tactile prepulse inhibition paradigm previously found to reveal activation in controls and deficient activation in schizophrenia patients in the striatum, thalamus, insula, hippocampal, temporal, inferior frontal, and inferior parietal regions.

Methods

Fourteen right-handed healthy men underwent psychophysiological testing and functional magnetic resonance imaging (fMRI) during a 15-min tactile PPI paradigm involving the use of tactile stimuli as both the pulse (a 40-ms presentation of 30 psi air-puff) and the prepulse (a 20-ms presentation of 6 psi air-puff presented 30-ms or 120-ms before the pulse). Individual differences in “psychosis-proneness” were assessed with Psychoticism scale of the Eysenck Personality Questionnaire-Revised (EPQ-R).

Results

High psychosis-proneness was associated with lower PPI and reduced activity in the inferior frontal gyrus, insula extending to putamen and thalamus, parahippocampal gyrus, and inferior parietal and middle temporal regions. No regional activity correlated positively with psychosis-proneness.

Conclusions

The present observations extend the findings observed previously in people with schizophrenia to people with high psychosis-proneness, providing support to continuum theories of psychosis with implications for understanding trait-related neural deficits in schizophrenia.

Type
Original article
Copyright
Copyright © European Psychiatric Association 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aasen, A.Kolli, L.Kumari, V.Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies. J Psychopharmacol 2005;19(1):3945.CrossRefGoogle ScholarPubMed
Abel, K.Waikar, M.Pedro, B.Hemsley, D.Geyer, M.Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls. J Psychopharmacol 1998;12:330337.CrossRefGoogle ScholarPubMed
Badcock, J.C.Smith, G.A.Rawlings, D.Temporal processing and psychosis proneness. Pers Individ Dif 1988;9(4):709719.CrossRefGoogle Scholar
Baruch, I.Hemsley, D.R.Gray, J.A.Latent inhibition and “psychotic proneness” in normal subjects. Pers Individ Dif 1988;9:777784.CrossRefGoogle Scholar
Becker, K.Laucht, M.El-Faddagh, M.Schmidt, M.H.The dopamine D4 receptor gene exon III polymorphism is associated with novelty seeking in 15-year-old males from a high-risk community sample. J Neural Transplant 2005;112:847858.CrossRefGoogle ScholarPubMed
Benjamin, J.Li, L.Patterson, C.Greenberg, B.D.Murphy, D.L.Hamer, D.H.Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nat Genet 1996;12:8184.CrossRefGoogle ScholarPubMed
Blumenthal, T.D.Creps, C.L.Normal startle responding in psychosis-prone college students. Pers Individ Dif 1994;17:345355.CrossRefGoogle Scholar
Braff, D.L.Information processing and attention dysfunctions in schizophrenia. Schizophr Bull 1993;19:233259.CrossRefGoogle Scholar
Braff, D.L.Geyer, M.A.Swerdlow, N.R.Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 2001;156(2–3):234258.CrossRefGoogle ScholarPubMed
Braff, D.L.Stone, C.Callaway, E.Geyer, M.Glick, I.Bali, L.Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 1978;15:339343.CrossRefGoogle ScholarPubMed
Cadenhead, K.S.Carasso, B.S.Swerdlow, N.R.Geyer, M.A.Braff, D.L.Prepulse inhibition and habituation are stable neurological measures in a normal male population. Biol Psychiatry 1999;45:360364.CrossRefGoogle Scholar
Cadenhead, K.S.Geyer, M.A.Braff, D.L.Impaired startle habituation and prepulse inhibition in patients with schizotypal personality disorder. Am J Psychiatry 1993;150:18621867.Google ScholarPubMed
Cadenhead, K.S.Swerdlow, N.R.Shafer, K.Diaz, M.Braff, D.L.Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in participants with schizotypal personality disorder: evidence of inhibitory deficits. Am J Psychiatry 2000;157:16601668.CrossRefGoogle Scholar
Chapman, L.J.Chapman, J.P.Kwapil, T.R.Eckblad, M.Zinser, M.C.Putatively psychosis-prone subjects 10 years later. J Abnorm Psychol 1994;103(2):171183.CrossRefGoogle ScholarPubMed
Claridge, G.Schizotypy: implications for illness and health. Oxford University Press; 1997.CrossRefGoogle Scholar
Cloninger, C.R.The tridimensional personality questionnaire. Department of Psychiatry and Genetics, Washington University School of Medicine; 1989.Google Scholar
Corr, P.J.Pickering, A.D.Gray, J.A.Personality and reinforcement in associative and instrumental learning. Pers Individ Dif 1995;19:4771.CrossRefGoogle Scholar
Csomor, PAStadler, RRFeldon, JYee, BKGeyer, MAVollenweider, FX.Haloperidol differentially modulates prepulse inhibition and P50 suppression in healthy humans stratified for low and high gating levels. Neuropsychopharmacology, 2007 Apr 25 [Epub ahead of print].Google ScholarPubMed
Della Casa, V.Hofer, I.Weiner, I.Feldon, J.The effects of smoking on acoustic prepulse inhibition in healthy men and women. Psychopharmacology 1998;137(4):362368.CrossRefGoogle ScholarPubMed
Duncan, E.Madonick, S.Chakravorty, S.Parwani, A.Szilagyi, S.Efferen, T.et al.Effects of smoking on acoustic startle and prepulse inhibition in humans. Psychopharmacology 2001;156(2–3):266272.CrossRefGoogle ScholarPubMed
Duncan, E.J.Szilagyi, S.Efferen, T.R.Schwartz, M.P.Parwani, A.Chakravorty, S.et al.Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia. Psychopharmacology 2003;167(1):6371.CrossRefGoogle Scholar
Ebstein, R.P.Novick, O.Umansky, R.Priel, B.Osher, Y.Blaine, D.et al.Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nat Genet 1996;12:7880.CrossRefGoogle ScholarPubMed
Evans, L.H.Gray, N.S.Snowden, R.J.Prepulse inhibition of startle and its moderation by schizotypy and smoking. Psychophysiology 2005;42(2):223231.CrossRefGoogle ScholarPubMed
Eysenck, H.J.The definition and measurement of psychoticism. Pers Individ Dif 1992;13(7):757785.CrossRefGoogle Scholar
Eysenck, H.J.Eysenck, S.B.G.Manual of the Eysenck personality scales. London: Hodder and Stoughton; 1991.Google Scholar
First, M.B.Spitzer, R.L.Gibbon, M.Williams, J.B.W.Structured clinical interview for DSM-IV axis I disorders. non-patient edition (SCID-1/NP), version 2 New York: New York State Psychiatric Institute, Biometrics Research; 1996.Google Scholar
Flaten, M.A.Test–retest reliability of the somatosensory blink reflex and its inhibition. Int J Psychophysiol 2002;45(3):261265.CrossRefGoogle ScholarPubMed
Friston, K.J.Holmes, A.P.Worsley, K.J.How many subjects constitute a study?. Neuroimage 1999;10:15.CrossRefGoogle ScholarPubMed
Friston, K.J.Williams, S.Howard, R.Frackwiak, R.S.Turner, R.Movement related effects in fMRI time series. Magn Reson Med 1996;35:346355.CrossRefGoogle ScholarPubMed
George, T.P.Termine, A.Sacco, K.A.Allen, T.M.Reutenauer, E.Vessicchio, J.C.et al.A preliminary study of the effects of cigarette smoking on prepulse inhibition in schizophrenia: involvement of nicotinic receptor mechanisms. Schizophr Res 2006;87(1–3):307315.CrossRefGoogle ScholarPubMed
Geyer, M.A.Swerdlow, N.R.Mansbach, R.S.Braff, D.L.Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res Bull 1990;25:485498.CrossRefGoogle Scholar
Gibbons, H.Rammsayer, T.H.Differential effects of personality traits related to the P-ImpUSS dimension on latent inhibition in healthy female subjects. Pers Individ Dif 1999;27:11571166.CrossRefGoogle Scholar
Graham, F.K.The more or less startling effects of weak prestimuli. Psychophysiology 1975;12:238248.CrossRefGoogle ScholarPubMed
Gray, N.S.Pickering, A.D.Gray, J.A.Psychoticism and dopamine D2 binding in the basal ganglia using single-photon emission tomography. Pers Individ Dif 1994;17:431434.CrossRefGoogle Scholar
Hazlett, E.A.Buchsbaum, M.S.Haznedar, M.M.Singer, M.B.Germans, M.K.Schnur, D.B.et al.Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients. Psychophysiology 1998;35:186198.CrossRefGoogle ScholarPubMed
Hazlett, E.A.Buchsbaum, M.S.Tang, C.Y.Fleischman, M.B.Wei, T.C.Byne, W.et al.Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study. Biol Psychiatry 2001;50(4):281291.CrossRefGoogle ScholarPubMed
Kumari, V.Antonova, E.Geyer, M.Ffytche, D.Williams, S.C.R.Sharma, T.An fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics. Int J Neuropsychopharmacol 2007;10(4):463477.CrossRefGoogle ScholarPubMed
Kumari, V.Antonova, E.Zachariah, E.Galea, A.Aasen, I.Ettinger, U.et al.Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans. Neuroimage 2005;26(4):10521058.CrossRefGoogle ScholarPubMed
Kumari, V.Checkley, S.A.Gray, J.A.Effect of cigarette smoking on prepulse inhibition of the acoustic startle reflex in healthy male smokers. Psychopharmacology 1996;128:5460.CrossRefGoogle ScholarPubMed
Kumari, V.Das, M.Hodgins, S.Zachariah, E.Barkataki, I.Howlett, M.et al.Association between violent behaviour and impaired prepulse inhibition of the startle response in antisocial personality disorder and schizophrenia. Behav Brain Res 2005;158(1):159166.CrossRefGoogle Scholar
Kumari, V.Das, M.Zachariah, E.Ettinger, U.Sharma, T.Reduced prepulse inhibition in unaffected siblings of schizophrenia patients. Psychophysiology 2005;42(5):588594.CrossRefGoogle ScholarPubMed
Kumari, V.Ettinger, U.Prepulse inhibition deficits in schizophrenia: static or amenable to treatment?. Lang, M.V.Progress in schizophrenia research. New York: Nova Publishers; 2005. 1-59454-154-X.Google Scholar
Kumari, V.Ettinger, U.Crawford, T.Zachariah, E.Sharma, T.Lack of association between prepulse inhibition and anti-saccadic deficits in schizophrenia: implications for identification of schizophrenia endophenotypes. J Psychiatr Res 2005;39(3):227240.CrossRefGoogle Scholar
Kumari, V.Fannon, D.G.Sumich, A.Sharma, T.Startle gating in antipsychotic-naïve first episode schizophrenia: one ear is better than two. Psychiatry Res 2007;151(1–2):2128.CrossRefGoogle ScholarPubMed
Kumari, V.Ffytche, D.H.Williams, S.C.R.Gray, J.A.Personality predicts brain responses to cognitive demands. J Neurosci 2004;24(47):1063610641.CrossRefGoogle ScholarPubMed
Kumari, V.Gray, J.A.Smoking withdrawal, nicotine dependence and prepulse inhibition of the acoustic startle reflex. Psychopharmacology 1999;141(1):1115.CrossRefGoogle ScholarPubMed
Kumari, V.Gray, J.A.Geyer, M.A.ffytche, D.Soni, W.Mitterschiffthaler, M.T.et al.Neural correlates of prepulse inhibition in normal and schizophrenic subjects: a functional MRI Study. Psychiatr Res: Neuroimag 2003;122:99113.CrossRefGoogle ScholarPubMed
Kumari, V.Gray, J.Gupta, P.Luscher, S.Sharma, T.Sex differences in prepulse inhibition of the acoustic startle response. Pers Individ Dif 2003;34:733742.CrossRefGoogle Scholar
Kumari, V.Soni, W.Sharma, T.Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia. Hum Psychopharmacol: Clin Exper 2001;16:321326.CrossRefGoogle Scholar
Kumari, V.Toone, B.Gray, J.A.Habituation and prepulse inhibition of the acoustic startle reflex: effects of smoking status and psychosis-proneness. Pers Individ Dif 1997;23:183191.CrossRefGoogle Scholar
Larrison, A.L.Briand, K.A.Sereno, A.B.Nicotine, caffeine, alcohol and schizotypy. Pers Individ Dif 1999;27(1):101108.CrossRefGoogle Scholar
Leumann, L.Feldon, J.Vollenweider, F.X.Ludewig, K.Effects of typical and atypical antipsychotics on prepulse inhibition and latent inhibition in chronic schizophrenia. Biol Psychiatry 2002;52:729739.CrossRefGoogle ScholarPubMed
Lipp, O.V.Siddle, D.A.T.Arnold, S.L.Psychosis proneness in a non-clinical sample II: a multi-experimental study of ‘‘attentional malfunctioning’’. Pers Individ Dif 1994;17(3):405424.CrossRefGoogle Scholar
Lubow, R.R.Ingbergsachs, Y.Zalsteunorda, N.Gewirtz, J.C.Latent inhibition in low and high psychotic-prone normal subjects. Pers Individ Dif 1992;13:563572.CrossRefGoogle Scholar
Ludewig, K.Geyer, M.A.Vollenweider, F.X.Deficits in prepulse inhibition and habituation in never-medicated first-episode schizophrenia. Biol Psychiatry 2003;54:121128.CrossRefGoogle ScholarPubMed
Meincke, U.Morth, D.Voss, T.Thelen, B.Geyer, M.A.Gouzoulis-Mayfrank, E.Prepulse inhibition of the acoustically evoked startle reflex in patients with an acute schizophrenic psychosis – a longitudinal study. Eur Arch Psychiatry Clin Neurosci 2004;254(6):415421.CrossRefGoogle ScholarPubMed
Noble, E.P.Ozkaragoz, T.Z.Ritchie, T.L.Zhang, X.X.Belin, T.R.Sparkes, R.S.D-2 and D-4 dopamine receptor polymorphisms and personality. Am J Med Genet 1998;81:257267.3.0.CO;2-E>CrossRefGoogle Scholar
O'Gorman, R.L.Kumari, V.Williams, S.C.R.Zelaya, F.O.Connor, S.E.J.Alsop, D.C.et al.Personality factors correlate with regional cerebral perfusion. Neuroimage 2006;31(2):489495.CrossRefGoogle ScholarPubMed
Ogawa, S.Lee, T.M.Kay, A.R.Tank, D.W.Brain magnetic resonance imaging with contrast dependent blood oxygenation. Proc Natl Acad Sci U S A 1990;87:88688872.CrossRefGoogle ScholarPubMed
Postma, P.Gray, J.A.Sharma, T.Geyer, M.Mehrotra, R.Das, M.et al.A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia. Psychopharmacology 2006;184(3–4):589599.CrossRefGoogle ScholarPubMed
Schwarzkopf, S.B.McCoy, L.Smith, D.A.Boutros, N.N.Test–retest reliability of prepulse inhibition of the acoustic startle response. Biol Psychiatry 1993;33:815828.CrossRefGoogle Scholar
Simmons, A.Moore, E.Williams, S.C.R.Quality control for functional magnetic resonance imaging using automated data analysis and showchart charting. Magn Reson Med 1997;41(6):12741278.3.0.CO;2-1>CrossRefGoogle Scholar
Simons, R.F.Giardina, B.D.Reflex modification in psychosis-prone young adults. Psychophysiology 1992;29(1):816.CrossRefGoogle ScholarPubMed
Stavridou, A.Furnham, A.The relationship between psychoticism, trait-creativity and the attentional mechanism of cognitive inhibition. Pers Individ Dif 1996;21(1):143153.CrossRefGoogle Scholar
Swerdlow, N.R.Auerbach, A.Monroe, S.M.Hartson, H.Geyer, M.A.Braff, D.L.Men are more inhibited than women by weak prepulses. Biol Psychiatry 1993;34:253260.CrossRefGoogle ScholarPubMed
Swerdlow, N.R.Filion, D.Geyer, M.A.Braff, D.L.“Normal” personality correlates of sensorimotor, cognitive, and visuospatial gating. Biol Psychiatry 1995;37(5):286299.CrossRefGoogle ScholarPubMed
Swerdlow, N.R.Geyer, M.A.Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 1998;24:285301.CrossRefGoogle Scholar
Swerdlow, N.R.Geyer, M.A.Braff, D.L.Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology 2001;156(2–3):194215.CrossRefGoogle ScholarPubMed
Swerdlow, N.R.Geyer, M.A.Hartman, P.L.Sprock, J.Auerbach, P.P.Cadenhead, K.et al.Sex differences in sensorimotor gating of the human startle response: all smoke?. Psychopharmacology 1999;146:228232.CrossRefGoogle ScholarPubMed
Swerdlow, N.R.Light, G.A.Cadenhead, K.S.Sprock, J.Hsieh, M.H.Braff, D.L.Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function. Arch Gen Psychiatry 2006;63(12):13251335.CrossRefGoogle Scholar
Swerdlow, N.R.Talledo, J.Sutherland, A.N.Nagy, D.Shoemaker, J.M.Antipsychotic effects on prepulse inhibition in normal ‘low gating’ humans and rats. Neuropsychopharmacology 2006;31(9):20112021.CrossRefGoogle ScholarPubMed
Thornton, J.C.Dawe, S.Lee, C.Capstick, C.Corr, P.J.Cotter, P.et al.Effects of nicotine and amphetamine on latent inhibition in human subjects. Psychopharmacology 1996;127:164173.CrossRefGoogle ScholarPubMed
Van Os, J.Is there a continuum of psychotic experiences in the general population?. Epidemiol Psichiatr Soc 2003;12:242252.CrossRefGoogle Scholar
Vollenweider, F.X.Barro, M.Csomor, P.A.Feldon, J.Clozapine enhances prepulse inhibition in healthy humans with low but not with high prepulse inhibition levels. Biol Psychiatry 2006;60(6):597603.CrossRefGoogle Scholar
Williams, J.H.Wellman, N.A.Allan, N.M.Taylor, E.Tonin, J.Feldon, J.et al.Tobacco smoking correlates with schizotypal and borderline personality traits. Pers Individ Dif 1996;20:267270.CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.