Skip to main content Accessibility help
×
Home

Automatic sensory information processing abnormalities across the illness course of schizophrenia

  • C. Jahshan (a1), K. S. Cadenhead (a2), A. J. Rissling (a2), K. Kirihara (a2), D. L. Braff (a2) and G. A. Light (a2)...

Abstract

Background

Deficits in automatic sensory discrimination, as indexed by a reduction in the mismatch negativity (MMN) and P3a event-related potential amplitudes, are well documented in chronic schizophrenia. However, MMN and P3a have not been sufficiently studied early in the course of psychotic illness. The present study aimed to investigate MMN, P3a and reorienting negativity (RON) across the course of schizophrenia.

Method

MMN, P3a, and RON were assessed in 118 subjects across four groups: (1) individuals at risk for psychosis (n=26); (2) recent-onset patients (n=31); (3) chronic patients (n=33); and (4) normal controls (n=28) using a duration-deviant auditory oddball paradigm.

Results

Frontocentral deficits in MMN and P3a were present in all patient groups. The at-risk group's MMN and P3a amplitudes were intermediate to those of the control and recent-onset groups. The recent-onset and chronic patients, but not the at-risk subjects, showed significant RON amplitude reductions, relative to the control group. Associations between MMN, P3a, RON and psychosocial functioning were present in the chronic patients. In the at-risk subjects, P3a and RON deficits were significantly associated with higher levels of negative symptoms.

Conclusions

Abnormalities in the automatic processes of sensory discrimination, orienting and reorienting of attention are evident in the early phases of schizophrenia and raise the possibility of progressive worsening across stages of the illness. The finding that MMN and P3a, but not RON, were reduced before psychosis onset supports the continued examination of these components as potential early biomarkers of schizophrenia.

Copyright

Corresponding author

*Address for correspondence: G. A. Light, Ph.D., Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA. (Email: glight@ucsd.edu)

References

Hide All
Addington, J, Saeedi, H, Addington, D (2005). The course of cognitive functioning in first episode psychosis: changes over time and impact on outcome. Schizophrenia Research 78, 3543.
Andreasen, NC (1984). Scale for the Assessment of Negative Symptoms (SANS). University of Iowa: Iowa City, Iowa.
Andreasen, NC, Endicott, J, Spitzer, RL, Winokur, G (1977). The family history method using diagnostic criteria. Reliability and validity. Archives of General Psychiatry 34, 12291235.
Ballon, JS, Kaur, T, Marks, II, Cadenhead, KS (2007). Social functioning in young people at risk for schizophrenia. Psychiatry Research 151, 2935.
Banati, R, Hickie, IB (2009). Therapeutic signposts: using biomarkers to guide better treatment of schizophrenia and other psychotic disorders. The Medical Journal of Australia 190, 2632.
Berti, S, Roeber, U, Schroger, E (2004). Bottom-up influences on working memory: behavioral and electrophysiological distraction varies with distractor strength. Experimental Psychology 51, 249257.
Bilder, RM, Goldman, RS, Robinson, D, Reiter, G, Bell, L, Bates, JA, Pappadopulos, E, Willson, DF, Alvir, JM, Woerner, MG, Geisler, S, Kane, JM, Lieberman, JA (2000). Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. American Journal of Psychiatry 157, 549559.
Braff, DL, Light, GA (2004). Preattentional and attentional cognitive deficits as targets for treating schizophrenia. Psychopharmacology (Berl) 174, 7585.
Brockhaus-Dumke, A, Tendolkar, I, Pukrop, R, Schultze-Lutter, F, Klosterkotter, J, Ruhrmann, S (2005). Impaired mismatch negativity generation in prodromal subjects and patients with schizophrenia. Schizophrenia Research 73, 297310.
Cadenhead, KS, Light, GA, Shafer, KM, Braff, DL (2005). P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment. Biological Psychiatry 57, 15041509.
Callaway, E, Naghdi, S (1982). An information processing model for schizophrenia. Archives of General Psychiatry 39, 339347.
Cannon, TD, Cadenhead, K, Cornblatt, B, Woods, SW, Addington, J, Walker, E, Seidman, LJ, Perkins, D, Tsuang, M, McGlashan, T, Heinssen, R (2008). Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Archives of General Psychiatry 65, 2837.
Chambers, WJ, Puig-Antich, J, Hirsch, M, Paez, P, Ambrosini, PJ, Tabrizi, MA, Davies, M (1985). The assessment of affective disorders in children and adolescents by semistructured interview. Test-retest reliability of the schedule for affective disorders and schizophrenia for school-age children, present episode version. Archives of General Psychiatry 42, 696702.
Devrim-Ucok, M, Keskin-Ergen, HY, Ucok, A (2008). Mismatch negativity at acute and post-acute phases of first-episode schizophrenia. European Archives of Psychiatry and Clinical Neuroscience 258, 179185.
Eastvold, AD, Heaton, RK, Cadenhead, KS (2007). Neurocognitive deficits in the (putative) prodrome and first episode of psychosis. Schizophrenia Research 93, 266277.
Escera, C, Alho, K, Winkler, I, Naatanen, R (1998). Neural mechanisms of involuntary attention to acoustic novelty and change. Journal of Cognitive Neuroscience 10, 590604.
Escera, C, Corral, M (2007). Role of mismatch negativity and novelty-P3 in involuntary auditory attention. Journal of Psychophysiology 21, 251264.
Escera, C, Yago, E, Alho, K (2001). Electrical responses reveal the temporal dynamics of brain events during involuntary attention switching. European Journal of Neuroscience 14, 877883.
First, MB, Spitzer, RL, Gibbon, M, Williams, JB (1995). Structured Clinical Interview for DSM-IV Axis I Disorders – Patient Edition (SCID-I/P, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute: New York.
Ford, JM, Roach, BJ, Miller, RM, Duncan, CC, Hoffman, RE, Mathalon, DH (2010). When it's time for a change: failures to track context in schizophrenia. International Journal of Psychophysiology 78, 3–13.
Friedman, D, Cycowicz, YM, Gaeta, H (2001). The novelty P3: an event-related brain potential (ERP) sign of the brain's evaluation of novelty. Neuroscience and Biobehavioral Reviews 25, 355373.
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.
Green, MF (1996). What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry 153, 321330.
Green, MF, Kern, RS, Braff, DL, Mintz, J (2000). Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the ‘right stuff’? Schizophrenia Bulletin 26, 119136.
Green, MF, Nuechterlein, KH (1999). Cortical oscillations and schizophrenia: timing is of the essence. Archives of General Psychiatry 56, 10071008.
Grillon, C, Courchesne, E, Ameli, R, Elmasian, R, Braff, D (1990 a). Effects of rare non-target stimuli on brain electrophysiological activity and performance. International Journal of Psychophysiology 9, 257267.
Grillon, C, Courchesne, E, Ameli, R, Geyer, MA, Braff, DL (1990 b). Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence. Archives of General Psychiatry 47, 171179.
Grzella, I, Muller, BW, Oades, RD, Bender, S, Schall, U, Zerbin, D, Wolstein, J, Sartory, G (2001). Novelty-elicited mismatch negativity in patients with schizophrenia on admission and discharge. Journal of Psychiatry and Neuroscience 26, 235246.
Hall, RC, Parks, J (1995). The modified global assessment of functioning scale: addendum. Psychosomatics 36, 416417.
Haroun, N, Dunn, L, Haroun, A, Cadenhead, KS (2006). Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. Schizophrenia Bulletin 32, 166178.
Heaton, RK, Gladsjo, JA, Palmer, BW, Kuck, J, Marcotte, TD, Jeste, DV (2001). Stability and course of neuropsychological deficits in schizophrenia. Archives of General Psychiatry 58, 2432.
Hermens, DF, Ward, PB, Hodge, MA, Kaur, M, Naismith, SL, Hickie, IB (2010). Impaired MMN/P3a complex in first-episode psychosis: cognitive and psychosocial associations. Progress in Neuropsychopharmacology and Biological Psychiatry 34, 822829.
Holig, C, Berti, S (2010). To switch or not to switch: brain potential indices of attentional control after task-relevant and task-irrelevant changes of stimulus features. Brain Research 1345, 164175.
Horton, J, Millar, A, Labelle, A, Knott, VJ (2011). MMN responsivity to manipulations of frequency and duration deviants in chronic, clozapine-treated schizophrenia patients. Schizophrenia Research 126, 202211.
Horvath, J, Winkler, I, Bendixen, A (2008). Do N1/MMN, P3a, and RON form a strongly coupled chain reflecting the three stages of auditory distraction? Biological Psychology 79, 139147.
Jahshan, C, Heaton, RK, Golshan, S, Cadenhead, KS (2010). Course of neurocognitive deficits in the prodrome and first episode of schizophrenia. Neuropsychology 24, 109120.
Javitt, DC (2009). Sensory processing in schizophrenia: neither simple nor intact. Schizophrenia Bulletin 35, 10591064.
Javitt, DC, Shelley, A, Ritter, W (2000 a). Associated deficits in mismatch negativity generation and tone matching in schizophrenia. Clinical Neurophysiology 111, 17331737.
Javitt, DC, Shelley, AM, Silipo, G, Lieberman, JA (2000 b). Deficits in auditory and visual context-dependent processing in schizophrenia: defining the pattern. Archives of General Psychiatry 57, 11311137.
Kasai, K, Okazawa, K, Nakagome, K, Hiramatsu, K, Hata, A, Fukuda, M, Honda, M, Miyauchi, M, Matsushita, M (1999). Mismatch negativity and N2b attenuation as an indicator for dysfunction of the preattentive and controlled processing for deviance detection in schizophrenia: a topographic event-related potential study. Schizophrenia Research 35, 141156.
Kawakubo, Y, Kamio, S, Nose, T, Iwanami, A, Nakagome, K, Fukuda, M, Kato, N, Rogers, MA, Kasai, K (2007). Phonetic mismatch negativity predicts social skills acquisition in schizophrenia. Psychiatry Research 152, 261265.
Kiang, M, Braff, DL, Sprock, J, Light, GA (2009). The relationship between preattentive sensory processing deficits and age in schizophrenia patients. Clinical Neurophysiology 120, 19491957.
Korostenskaja, M, Dapsys, K, Siurkute, A, Maciulis, V, Ruksenas, O, Kahkonen, S (2005). Effects of olanzapine on auditory P300 and mismatch negativity (MMN) in schizophrenia spectrum disorders. Progress in Neuro-psychopharmacology and Biological Psychiatry 29, 543548.
Kristensen, K, Cadenhead, KS (2007). Cannabis abuse and risk for psychosis in a prodromal sample. Psychiatry Research 151, 151154.
Leitman, DI, Sehatpour, P, Higgins, BA, Foxe, JJ, Silipo, G, Javitt, DC (2010). Sensory deficits and distributed hierarchical dysfunction in schizophrenia. American Journal of Psychiatry 167, 818827.
Lencz, T, Smith, CW, McLaughlin, D, Auther, A, Nakayama, E, Hovey, L, Cornblatt, BA (2006). Generalized and specific neurocognitive deficits in prodromal schizophrenia. Biological Psychiatry 59, 863871.
Light, GA, Braff, DL (2005 a). Mismatch negativity deficits are associated with poor functioning in schizophrenia patients. Archives of General Psychiatry 62, 127136.
Light, GA, Braff, DL (2005 b). Stability of mismatch negativity deficits and their relationship to functional impairments in chronic schizophrenia. American Journal of Psychiatry 162, 17411743.
Light, GA, Geyer, MA, Clementz, BA, Cadenhead, KS, Braff, DL (2000). Normal P50 suppression in schizophrenia patients trated with atypical antipsychotic medications. American Journal of Psychiatry 157, 767771.
Light, GA, Hsu, JL, Hsieh, MH, Meyer-Gomes, K, Sprock, J, Swerdlow, NR, Braff, DL (2006). Gamma band oscillations reveal neural network cortical coherence dysfunction in schizophrenia patients. Biological Psychiatry 60, 12311240.
Light, GA, Swerdlow, NR, Braff, DL (2007). Preattentive sensory processing as indexed by the MMN and P3a brain responses is associated with cognitive and psychosocial functioning in healthy adults. Journal of Cognitive Neuroscience 19, 16241632.
Light, GA, Williams, LE, Minow, F, Sprock, J, Rissling, A, Sharp, R, Swerdlow, NR, Braff, DL (2010). Electroencephalography (EEG) and event-related potentials (ERPs) with human participants. Current Protocols in Neuroscience Chapter 6, Unit 6.25, 124.
Mathalon, DH, Ford, JM, Pfefferbaum, A (2000). Trait and state aspects of P300 amplitude reduction in schizophrenia: a retrospective longitudinal study. Biological Psychiatry 47, 434449.
Mesholam-Gately, RI, Giuliano, AJ, Goff, KP, Faraone, SV, Seidman, LJ (2009). Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology 23, 315336.
Michie, PT, Innes-Brown, H, Todd, J, Jablensky, AV (2002). Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders. Biological Psychiatry 52, 749758.
Miller, TJ, McGlashan, TH, Rosen, JL, Cadenhead, K, Cannon, T, Ventura, J, McFarlane, W, Perkins, DO, Pearlson, GD, Woods, SW (2003). Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophrenia Bulletin 29, 703715.
Naatanen, R, Gaillard, AW, Mantysalo, S (1978). Early selective-attention effect on evoked potential reinterpreted. Acta Psychologica 42, 313329.
Naatanen, R, Simpson, M, Loveless, NE (1982). Stimulus deviance and evoked potentials. Biological Psycholology 14, 5398.
Oades, RD, Wild-Wall, N, Juran, SA, Sachsse, J, Oknina, LB, Ropcke, B (2006). Auditory change detection in schizophrenia: sources of activity, related neuropsychological function and symptoms in patients with a first episode in adolescence, and patients 14 years after an adolescent illness-onset. BMC Psychiatry 6, 7.
Otten, LJ, Alain, C, Picton, TW (2000). Effects of visual attentional load on auditory processing. Neuroreport 11, 875880.
Palmer, BW, Dawes, SE, Heaton, RK (2009). What do we know about neuropsychological aspects of schizophrenia? Neuropsychology Review 19, 365384.
Pfohl, B, Blum, N, Zimmerman, M (1995). The Structured Interview for DSM-IV Personality (SIDP-IV). Department of Psychiatry, University of Iowa: Iowa City, Iowa.
Picton, TW, Alain, C, Otten, L, Ritter, W, Achim, A (2000). Mismatch negativity: different water in the same river. Audiology and Neurotology 5, 111139.
Quednow, BB, Frommann, I, Berning, J, Kuhn, KU, Maier, W, Wagner, M (2008). Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia. Biological Psychiatry 64, 766773.
Rasser, PE, Schall, U, Todd, J, Michie, PT, Ward, PB, Johnston, P, Helmbold, K, Case, V, Soyland, A, Tooney, PA, Thompson, PM (2011). Gray matter deficits, mismatch negativity, and outcomes in schizophrenia. Schizophrenia Bulletin 37, 131140.
Rissling, AJ, Light, GA (2010). Neurophysiological measures of sensory registration, stimulus discrimination, and selection in schizophrenia patients. Current Topics in Behavioral Neurosciences 4, 283309.
Rissling, AJ, Makeig, S, Braff, DL, Light, GA (2010). Neurophysiologic markers of abnormal brain activity in schizophrenia. Current Psychiatry Reports 12, 572578.
Salisbury, DF, Kuroki, N, Kasai, K, Shenton, ME, McCarley, RW (2007). Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia. Archives of General Psychiatry 64, 521529.
Salisbury, DF, Shenton, ME, Griggs, CB, Bonner-Jackson, A, McCarley, RW (2002). Mismatch negativity in chronic schizophrenia and first-episode schizophrenia. Archives of General Psychiatry 59, 686694.
Schroger, E, Giard, MH, Wolff, C (2000). Auditory distraction: event-related potential and behavioral indices. Clinical Neurophysiology 111, 14501460.
Schroger, E, Wolff, C (1998). Attentional orienting and reorienting is indicated by human event-related brain potentials. Neuroreport 9, 33553358.
Seeber, K, Cadenhead, KS (2005). How does studying schizotypal personality disorder inform us about the prodrome of schizophrenia? Current Psychiatry Reports 7, 4150.
Seidman, LJ, Giuliano, AJ, Meyer, EC, Addington, J, Cadenhead, KS, Cannon, TD, McGlashan, TH, Perkins, DO, Tsuang, MT, Walker, EF, Woods, SW, Bearden, CE, Christensen, BK, Hawkins, K, Heaton, R, Keefe, RS, Heinssen, R, Cornblatt, BA (2010). Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Archives of General Psychiatry 67, 578588.
Semlitsch, HV, Anderer, P, Schuster, P, Presslich, O (1986). A solution for reliable and valid reduction of ocular artifacts, applied to the P300 ERP. Psychophysiology 23, 695703.
Shelley, AM, Ward, PB, Catts, SV, Michie, PT, Andrews, S, McConaghy, N (1991). Mismatch negativity: an index of a preattentive processing deficit in schizophrenia. Biological Psychiatry 30, 10591062.
Turetsky, BI, Bilker, WB, Siegel, SJ, Kohler, CG, Gur, RE (2009). Profile of auditory information-processing deficits in schizophrenia. Psychiatry Research 165, 2737.
Umbricht, D, Javitt, D, Novak, G, Bates, J, Pollack, S, Lieberman, J, Kane, J (1998). Effects of clozapine on auditory event-related potentials in schizophrenia. Biological Psychiatry 44, 716725.
Umbricht, D, Javitt, D, Novak, G, Bates, J, Pollack, S, Lieberman, J, Kane, J (1999). Effects of risperidone on auditory event-related potentials in schizophrenia. International Journal of Neuropsychopharmacology 2, 299304.
Umbricht, D, Krljes, S (2005). Mismatch negativity in schizophrenia: a meta-analysis. Schizophrenia Research 76, 123.
Umbricht, DS, Bates, JA, Lieberman, JA, Kane, JM, Javitt, DC (2006). Electrophysiological indices of automatic and controlled auditory information processing in first-episode, recent-onset and chronic schizophrenia. Biological Psychiatry 59, 762772.
Valkonen-Korhonen, M, Purhonen, M, Tarkka, IM, Sipila, P, Partanen, J, Karhu, J, Lehtonen, J (2003). Altered auditory processing in acutely psychotic never-medicated first-episode patients. Brain Research 17, 747758.
Woldorff, MG, Hackley, SA, Hillyard, SA (1991). The effects of channel-selective attention on the mismatch negativity wave elicited by deviant tones. Psychophysiology 28, 3042.
Woldorff, MG, Hillyard, SA, Gallen, CC, Hampson, SR, Bloom, FE (1998). Magnetoencephalographic recordings demonstrate attentional modulation of mismatch-related neural activity in human auditory cortex. Psychophysiology 35, 283292.
Wynn, JK, Sugar, C, Horan, WP, Kern, R, Green, MF (2010). Mismatch negativity, social cognition, and functioning in schizophrenia patients. Biological Psychiatry 67, 940947.
Yung, AR, McGorry, PD (1996). The initial prodrome in psychosis: descriptive and qualitative aspects. The Australian and New Zealand Journal of Psychiatry 30, 587599.
Yung, AR, Yuen, HP, McGorry, PD, Phillips, LJ, Kelly, D, Dell'Olio, M, Francey, SM, Cosgrave, EM, Killackey, E, Stanford, C, Godfrey, K, Buckby, J (2005). Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States. The Australian and New Zealand Journal of Psychiatry 39, 964971.

Keywords

Automatic sensory information processing abnormalities across the illness course of schizophrenia

  • C. Jahshan (a1), K. S. Cadenhead (a2), A. J. Rissling (a2), K. Kirihara (a2), D. L. Braff (a2) and G. A. Light (a2)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed