Pharmacopsychiatry 2011; 44(3): 102-108
DOI: 10.1055/s-0031-1271687
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Short-Term Prospective Comparison of Prepulse Inhibition between Schizophrenic Patients and Healthy Controls

U. W. Preuss1 , J. Zimmermann2 , S. Watzke1 , J. Langosch2 , N. Siafarikas1 , J. W. M. Wong3 , A. Hamm4 , A. Weike4
  • 1Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany
  • 2Krankenhaus Bethanien, Hospital for Psychiatry and Psychotherapy, Johanna-Odebrecht-Foundation, Greifswald, Germany
  • 3AWO Psychiatriezentrum Halle (Saale), Institut für Psychologie, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
  • 4Institut für Psychologie, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
Further Information

Publication History

received 05.08.2010 revised 07.11.2010

accepted 03.01.2011

Publication Date:
22 March 2011 (online)

Abstract

Introduction: The prepulse inhibition (PPI) of acoustic startle reflex is impaired in schizophrenic individuals compared to normal controls, and has been suggested to be a biomarker for sensorimotor gating. In fact, some cross-sectional studies suggest a different type of effect on PPI changes depending on the kind of antipsychotic treatment but few prospective studies have been conducted to investigate the short-term course of PPI alterations during the first few weeks of treatment. This study aimed to investigate schizophrenic subjects and controls over 4 weeks to analyze the course of PPI changes between groups at baseline and during follow-up, to determine whether potential PPI alterations are influenced by type of antipsychotic medication and whether these alterations are accompanied by changes in psychopathology.

Methods: 39 schizophrenic patients and 39 controls were enrolled into this open prospective trial. Acoustic startle response (PPI) measurements and clinical (PANSS) performance were obtained shortly after admission and every 14 days for a 4-week follow-up period (T1 to T3).

Results: Patients were treated with first and/or second generation antipsychotics in an open-label design. At baseline (T1) significant deficits were detected between schizophrenic subjects and controls for several PPI conditions. Neither was a relationship between type of antipsychotic treatment and PPI measures detected at baseline and during follow-up, nor was any association with PANSS psychopathology found.

Discussion: The results of our study confirm previous research on PPI deficits in schizophrenic subjects. As with previous prospective PPI studies in schizophrenic subjects, initial PPI deficits were not observed during the follow-up period, independent of the kind of antipsychotic treatment and severity of psychopathology. These findings may indicate that PPI serves as a biological marker of schizophrenic psychosis and sensorimotor gating independent of type of antipsychotic administered or severity of psychotic symptoms.

References

  • 1 Aasen I, 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 39-45
  • 2 Addington J, Cadenhead KS, Cannon TD et al. North American Prodrome Longitudinal Study. North American Prodrome Longitudinal Study: a collaborative multisite approach to prodromal schizophrenia research.  Schizophr Bull. 2007;  33 665-672
  • 3 Andreasen NC. The Scale for the Assessment of Negative Symptoms (SANS). The University of Iowa; Iowa City, IA; 1983
  • 4 Bitsios P, Giakoumaki SG. Relationship of prepulse inhibition of the startle reflex to attentional and executive mechanisms in man.  Int J Psychophysiol. 2005;  55 229-241
  • 5 Bleuler E. Dementia praecox; or, the group of schizophrenias. International Universities Press, New York; 1911/1950
  • 6 Braff D, Stone C, Callaway E et al. Prestimulus effects on human startle reflex in normals and schizophrenics.  Psychophysiology. 1978;  15 339-343
  • 7 Braff D, Geyer MA. Sensorimotor gating and schizophrenia. Human and animal model studies.  Arch Gen Psychiatry Rev. 1990;  47 181-188
  • 8 Braff DL, Grillon C, Geyer MA. Gating and habituation of the startle reflex in schizophrenic patients.  Arch Gen Psychiatry. 1992;  49 206-215
  • 9 Braff DL, Swerdlow NR, Geyer MA. Symptom correlates of prepulse inhibition deficits in male schizophrenic patients.  Am J Psychiatry. 1999;  156 596-602
  • 10 Braff DL, Geyer MA, Swerdlow NR. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.  Psychopharmacology. 2001;  156 234-258
  • 11 Cadenhead KS, Geyer MA, Braff DL. Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder.  Am J Psychiatry. 1993;  150 1862-1867
  • 12 Cadenhead KS, Light GA, Geyer MA et al. Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder.  Am J Psychiatry. 2000;  157 55-59
  • 13 Cadenhead KS, Swerdlow NR, Shafer KM et al. Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: Evidence of inhibitory deficits.  Am J Psychiatry. 2000;  157 1660-1668
  • 14 Cannon TD, Cadenhead K, Cornblatt B et al. Prediction of psychosis in youth at high clinical risk: a multi-site longitudinal study in North America.  Arch Gen Psychiatry. 2008;  65 28-37
  • 15 Carlsson A. The current status of the dopamine hypothesis of schizophrenia.  Neuropsychopharmacology. 1988;  1 179-186
  • 16 Chouinard G, Ross-Chouinard A. Manual: Extrapyramidal Symptom Rating Scale (ESRS). Department of Psychiatry, McGill University, Montreal; 1979
  • 17 Duncan E, Szilagyi S, Schwarts M et al. Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol.  Psychiatry Res. 2003;  120 1-12
  • 18 Duncan E, Szilagyi S, Schwartz M et al. Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia.  Psychopharmacology (Berl). 2003;  167 63-71
  • 19 Galecki AT. General class of covariance structures for two or more repeated factors in longitudinal data analysis.  Communications in Statistics. 1994;  23 3105-3120
  • 20 Graham F. The more or less startling effects of weak prestimuli.  Psychophysiology. 1975;  12 238-248
  • 21 Grillon C, Ameli R, Charney DS et al. Startle gating deficits occur across prepulse intensities in schizophrenic patients.  Biol Psychiatry. 1992;  32 939-943
  • 22 Grillon C, Morgan 3rd CA, Davis M et al. Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder.  Biol Psychiatry. 1998;  44 1027-1036
  • 23 Guy E. Abnormal Involuntary Movement Scale. Rockville, MD, National Institute of Mental Health, U.S. Department of Health and Human Services; ECDEU Assessment Manual for Psychopharmacology: rev 1976
  • 24 Häfner H, Löffler W, Maurer K et al. IRAOS – Interview für die retrospektive Erfassung des Krankheitsbeginns und -verlaufs bei Schizophrenie und anderen Psychosen. Bern: Huber; 1999
  • 25 Jovanovic T, Szilagyi S, Chakravorthy S et al. Menstrual cycle phase effects on prepulse inhibition of acoustic startle.  Psychophysiology. 2004;  41 401-406
  • 26 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia.  Schizophrenia Bulletin. 1987;  13 261-276
  • 27 Kraepelin E, Robertson GM. Dementia praecox and paraphrenia. Edinburgh: Livingstone; 1919
  • 28 Kumari V, Soni W, Sharma T. Normalization of information processing deficits in schizophrenia with clozapine.  Am J Psychiatry. 1999;  156 1046-1051
  • 29 Kumari V, Soni W, Mathew VM et al. Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication.  Arch Gen Psychiatry. 2000;  57 609-614
  • 30 Kumari V, Soni W, Sharma T. Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics.  Schizophr Res. 2002;  55 139-146
  • 31 Kumari V, Sharma T. Effects of typical and atypical antipsychotics on prepulse inhibition in schizophrenia: a critical evaluation of current evidence and directions for future research.  Psychopharmacology (Berl). 2002;  162 97-101
  • 32 Kumari V, Aasen I, Sharma T. Sex differences in prepulse inhibition deficits in chronic schizophrenia.  Schizophr Res. 2004;  69 219-235
  • 33 Leumann L, Feldon J, Vollenweider FX et al. Effects of typical and atypical antipsychotics on prepulse inhibition and latent inhibition in chronic schizophrenia.  Biol Psychiatry. 2002;  52 729-739
  • 34 Ludewig K, Geyer MA, Etzensberger M et al. Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia.  Schizophr Res. 2002;  55 129-137
  • 35 Mackeprang T, Kristiansen KT, Glenthoj BY. Effects of antipsychotics on prepulse inhibition of the startle response in drug-naive schizophrenic patients.  Biol Psychiatry. 2002;  52 863-873
  • 36 McGhie A, Chapman J. Disorders of attention and perception in early schizophrenia.  Brit J Med Psychol. 1961;  34 103-116
  • 37 Meincke U, Mörth D, Voss T et al. Prepulse inhibition of the acoustically evoked startle reflex in patients with an acute schizophrenic psychosis – a longitudinal study.  Eur Arch Psychiatry Clin Neurosci. 2004;  254 415-421
  • 38 Minassian A, Feifel D, Perry W et al. The relationship between sensorimotor gating and clinical improvement in acutely ill schizophrenia patients.  Schizophr Res. 2007;  89 225-231
  • 39 Oranje B, Van Oel CJ, Gispen-De Wied CC et al. Effects of typical and atypical antipsychotics on the prepulse inhibition of the startle reflex in patients with schizophrenia.  J Clin Psychopharmacol. 2002;  22 359-365
  • 40 Parwani A, Duncan EJ, Barlett E et al. Impaired prepulse inhibition of acoustic startle in schizophrenia.  Biol Psychiatry. 2000;  47 662-669
  • 41 Perry W, Feifel D, Minassian A et al. Information processing deficits in acutely psychotic schizophrenia patients medicated and unmedicated at the time of admission.  Am J Psychiatry. 2002;  159 1375-1381
  • 42 Preuss UW, Zetzsche T, Jäger M et al. Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric MRI study.  Schizophr Res. 2005;  73 91-101
  • 43 Quednow BB, Wagner M, Westheide J et al. Sensorimotor gating and habituation of the startle response in schizophrenic patients randomly treated with amisulpride or olanzapine.  Biol Psychiatry. 2006;  59 536-545
  • 44 Swerdlow NR, Filion D, Geyer MA et al. “Normal” personality correlates of sensorimotor, cognitive and visuo-spatial gating.  Biol Psychiatry. 1995;  37 286-299
  • 45 Swerdlow NR, Hartman PL, Auerbach PP. Changes in sensorimotor inhibition across the menstrual cycle: Implications for neuropsychiatric disorders.  Biol Psychiatry. 1997;  41 452-460
  • 46 Swerdlow NR, Light GA, Cadenhead KS et al. 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 1325-1335
  • 47 Swerdlow NR, Weber M, Qu Y et al. Realistic expectations of prepulse inhibition in translational models for schizophrenia research.  Psychopharmacology (Berl). 2008;  199 331-388
  • 48 van der Linden D, Massar SA, Schellekens AF et al. Disrupted sensorimotor gating due to mental fatigue: preliminary evidence.  Int J Psychophysiol. 2006;  62 168-174
  • 49 Venables P. The effect of auditory and visual stimulation on skin potential responses of schizophrenics.  Brain. 1960;  83 77-92
  • 50 Vollenweider FX, Barro M, Csomor PA et al. Clozapine enhances prepulse inhibition in healthy humans with low but not with high prepulse inhibition levels.  Biol Psychiatry. 2006;  60 597-603
  • 51 Weike AJ, Bauer U, Hamm AO et al. Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients.  Biol Psychiatry. 2000;  47 61-70
  • 52 Wittchen HU, Zaudig M, Fydrich T. SKID: Strukturiertes klinisches Interview für DSM-IV. Göttingen: Hogrefe; 1997
  • 53 Wynn JK, Green MF, Sporck J et al. Effects of olanzapine, risperidone and haloperidol on prepulse inhibition in schizophrenia patients: A double-blind, randomized controlled trial.  Schizophr Res. 2007;  95 134-142
  • 54 American Psychiatric Association .DSM IV-TR: Diagnostic and statistical manual of mental disorders – Text revision (Fourth ed.). Washington, D.C.: American Psychiatric Association; 2000
  • 55 Woods SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics.  J Clin Psychiatry. 2003;  64 663-667
  • 56 Möller HJ, Müller ME, Volz HP. Psychopharmakotherapie. Ein Leitfaden für Klinik und Praxis. 2.  Auflage, Kohlhammer, Stuttgart 2000; 

Correspondence

U. W. PreussMD 

Department of Psychiatry,

Psychotherapy and

Psychosomatics

Martin-Luther-University of

Halle-Wittenberg

Julius-Kühn-Straße 7

06097 Halle/ Saale

Germany

Phone: +49/345/557 4595

Fax: +49/345/557 3500

Email: ulrich.preuss@medizin.uni-halle.de