Hostname: page-component-669899f699-cf6xr Total loading time: 0 Render date: 2025-04-25T07:49:53.068Z Has data issue: false hasContentIssue false
  • English
  • Français

Selective attention and mismatch negativity in antipsychotic-naïve, first-episode schizophrenia patients before and after 6 months of antipsychotic monotherapy

Published online by Cambridge University Press:  26 April 2017

B. Oranje ,
B. Aggernaes ,
H. Rasmussen ,
B. H. Ebdrup  and
B. Y. Glenthøj
B. Oranje*
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Services Glostrup, Capital Region Denmark, Glostrup, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
B. Aggernaes
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Services Glostrup, Capital Region Denmark, Glostrup, Denmark
H. Rasmussen
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Services Glostrup, Capital Region Denmark, Glostrup, Denmark
B. H. Ebdrup
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Services Glostrup, Capital Region Denmark, Glostrup, Denmark
B. Y. Glenthøj
Affiliation:
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Services Glostrup, Capital Region Denmark, Glostrup, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
*
*Address for correspondence: B. Oranje, Ph.D., Center for Neuropsychiatric Schizophrenia Research, University Psychiatric Center Glostrup, Ndr. Ringvej 29-67, DK-2600 Glostrup, Denmark. (Email: B.Oranje@cnsr.dk)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2 receptors than for serotonergic 5-HT2A receptors, on electrophysiological parameters of attention was investigated in a group of antipsychotic-naïve, first-episode schizophrenia patients compared with a group of age- and gender-matched healthy controls.

Method

A total of 34 first-episode, antipsychotic-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow-up, whereas controls received no treatment.

Results

Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only ameliorated in patients treated with above median dosages of quetiapine. Patients had lower P3B amplitude, yet showed similar levels of processing negativity and N100 amplitude compared with healthy controls, both at baseline and follow-up.

Conclusions

The results indicate that deficits in MMN, P200 and P3B amplitude are present at early stages of schizophrenia, although depending on the paradigm used. Furthermore, the results indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits, and only in those subjects on higher dosages.

Keywords

Antipsychotic naïve first episode schizophreniaquetiapinemismatch negativityselective attentionelectrophysiology
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 12 , September 2017 , pp. 2155 - 2165
Copyright
Copyright © Cambridge University Press 2017 

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.)

Article purchase

Temporarily unavailable

References

Aggernaes, B, Glenthoj, BY, Ebdrup, BH, Rasmussen, H, Lublin, H, Oranje, B (2010). Sensorimotor gating and habituation in antipsychotic-naïve, first-episode schizophrenia patients before and after six months treatment with quetiapine. International Journal of Neuropsychopharmacology 13, 1383–1395.CrossRefGoogle Scholar
Ahveninen, J, Kähkönen, S, Pennanen, S, Liesivuori, J, Ilmoniemi, RJ, Jääskeläinen, IP (2002). Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans. NeuroImage 16, 1052–1061.CrossRefGoogle ScholarPubMed
Bramon, E, McDonald, C, Croft, RJ, Landau, S, Filbey, F, Gruzelier, JH, Sham, PC, Frangou, S, Murray, RM (2005). Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study. NeuroImage 27, 960–968.CrossRefGoogle Scholar
Bramon, E, Rabe-Hesketh, S, Sham, P, Murray, RM, Frangou, S (2004). Meta-analysis of the P300 and P50 waveforms in schizophrenia. Schizophrenia Research 70, 315–329.CrossRefGoogle ScholarPubMed
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, 179–185.CrossRefGoogle ScholarPubMed
Ferreira-Santos, F, Silveira, C, Almeida, PR, Palha, A, Barbosa, F, Marques-Teixeira, J (2012). The auditory P200 is both increased and reduced in schizophrenia? A meta-analytic dissociation of the effect for standard and target stimuli in the oddball task. Clinical Neurophysiology 123, 1300–1308.CrossRefGoogle ScholarPubMed
Frodl Bauch, T, Bottlender, R, Hegerl, U (1999). Neurochemical substrates and neuroanatomical generators of the event-related P300. Neuropsychobiology 40, 86–94.CrossRefGoogle ScholarPubMed
Goldberg, TE, Goldman, RS, Burdick, KE, Malhotra, AK, Lencz, T, Patel, RC, Woerner, MG, Schooler, NR, Kane, JM, Robinson, DG (2007). Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Archives of General Psychiatry 64, 1115–1122.CrossRefGoogle ScholarPubMed
Gunduz-Bruce, H, Reinhart, RM, Roach, BJ, Gueorguieva, R, Oliver, S, D'Souza, DC, Ford, JM, Krystal, JH, Mathalon, DH (2012). Glutamatergic modulation of auditory information processing in the human brain. Biological Psychiatry 71, 969–977.CrossRefGoogle ScholarPubMed
Hall, MH, Rijsdijk, F (2008). Validating endophenotypes for schizophrenia using statistical modeling of twin data. Clinical EEG Neuroscience 39, 78–81.CrossRefGoogle ScholarPubMed
Hay, RA, Roach, BJ, Srihari, VH, Woods, SW, Ford, JM, Mathalon, DH (2015). Equivalent mismatch negativity deficits across deviant types in early illness schizophrenia-spectrum patients. Biological Psychology 105, 130–137.CrossRefGoogle ScholarPubMed
Huang, WJ, Chen, WW, Zhang, X (2015). The neurophysiology of P 300 – an integrated review. European Review of Medical and Pharmacological Sciences 19, 1480–1488.Google ScholarPubMed
Ille, N, Berg, P, Scherg, M (2002). Artifact correction of the ongoing EEG using spatial filters based on artifact and brain signal topographies. Journal of Clinical Neurophysiology 19, 113–124.CrossRefGoogle ScholarPubMed
Iwanami, A, Isono, H, Okajima, Y, Noda, Y, Kamijima, K (1998). Event-related potentials during a selective attention task with short interstimulus intervals in patients with schizophrenia. Journal of Psychiatry and Neuroscience 23, 45–50.Google ScholarPubMed
Javitt, DC, Doneshka, P, Grochowski, S, Ritter, W (1995). Impaired mismatch negativity generation reflects widespread dysfunction of working memory in schizophrenia. Archives of General Psychiatry 52, 550–558.CrossRefGoogle ScholarPubMed
Javitt, DC, Steinschneider, M, Schroeder, CE, Arezzo, JC (1996). Role of cortical N-methyl-d-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia. Proceedings of the National Academy of Sciences USA 93, 11962–11967.CrossRefGoogle ScholarPubMed
Jensen, KS, Oranje, B, Wienberg, M, Glenthoj, BY (2007). The effects of increased central serotonergic activity on prepulse inhibition and habituation of the human startle response. Neuropsychopharmacology 32, 2117–2124.CrossRefGoogle ScholarPubMed
Jensen, KS, Oranje, B, Wienberg, M, Glenthoj, BY (2008). The effects of increased serotonergic activity on human sensory gating and its neural generators. Psychopharmacology 196, 631–641.CrossRefGoogle ScholarPubMed
Jeon, YW, Polich, J (2003). Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical implications. Psychophysiology 40, 684–701.CrossRefGoogle ScholarPubMed
Kähkönen, S, Makinen, V, Jaaskelainen, IP, Pennanen, S, Liesivuori, J, Ahveninen, J (2005). Serotonergic modulation of mismatch negativity. Psychiatry Research 138, 61–74.CrossRefGoogle ScholarPubMed
Kalkstein, S, Hurford, I, Gur, RC (2010). Neurocognition in schizophrenia. Current Topics of Behavioural Neuroscience 4, 373–390.CrossRefGoogle ScholarPubMed
Kapur, S, Zipursky, R, Jones, C, Shammi, CS, Remington, G, Seeman, P (2000). A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Archives of General Psychiatry 57, 553–559.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.CrossRefGoogle ScholarPubMed
Keefe, RS, Harvey, PD (2012). Cognitive impairment in schizophrenia. Handbook of Experimental Pharmacology 2012, 11–37.CrossRefGoogle Scholar
Korostenskaja, M, Dapsys, K, Siurkute, A, Maciulis, V, Ruksenas, O, Kähkönen, S (2005). Effects of olanzapine on auditory P300 and mismatch negativity (MMN) in schizophrenia spectrum disorders. Progress in Neuropsychopharmacology and Biological Psychiatry 29, 543–548.CrossRefGoogle ScholarPubMed
Lieberman, JA, Mailman, RB, Duncan, G, Sikich, L, Chakos, M, Nichols, DE, Kraus, JE (1998). Serotonergic basis of antipsychotic drug effects in schizophrenia. Biological Psychiatry 44, 1099–1117.CrossRefGoogle ScholarPubMed
Light, GA, Braff, DL (2005). Mismatch negativity deficits are associated with poor functioning in schizophrenia patients. Archives of General Psychiatry 62, 127–136.CrossRefGoogle ScholarPubMed
Magno, E, Yeap, S, Thakore, JH, Garavan, H, De Sanctis, P, Foxe, JJ (2008). Are auditory-evoked frequency and duration mismatch negativity deficits endophenotypic for schizophrenia? High-density electrical mapping in clinically unaffected first-degree relatives and first-episode and chronic schizophrenia. Biological Psychiatry 64, 385–391.CrossRefGoogle ScholarPubMed
Meltzer, HY, Li, Z, Kaneda, Y, Ichikawa, J (2003). Serotonin receptors: their key role in drugs to treat schizophrenia. Progress in Neuro-psychopharmacology and Biological Psychiatry 27, 1159–1172.CrossRefGoogle ScholarPubMed
Metting van Rijn, AC, Kuiper, AP, Dankers, TE, Grimbergen, CA (1996). Low-cost active electrode improves the resolution in biopotential recordings. In Proceedings of the 18th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Amsterdam, The Netherlands, pp. 101–102.Google Scholar
Michie, PT, Budd, TW, Todd, J, Rock, D, Wichmann, H, Box, J, Jablensky, AV (2000). Duration and frequency mismatch negativity in schizophrenia. Clinical Neurophysiology 111, 1054–1065.CrossRefGoogle ScholarPubMed
Michie, PT, Fox, AM, Ward, PB, Catts, SV, McConaghy, N (1990). Event-related potential indices of selective attention and cortical lateralization in schizophrenia. Psychophysiology 27, 209–227.CrossRefGoogle ScholarPubMed
Mirsky, AF, Anthony, BJ, Duncan, CC, Ahearn, MB, Kellam, SG (1991). Analysis of the elements of attention: a neuropsychological approach. Neuropsychology Review 2, 109–145.CrossRefGoogle ScholarPubMed
Molina, V, Munoz, F, Martin-Loeches, M, Casado, P, Hinojosa, JA, Iglesias, A (2004). Long-term olanzapine treatment and P300 parameters in schizophrenia. Neuropsychobiology 50, 182–188.CrossRefGoogle ScholarPubMed
Näätänen, R (1990). The role of attention in auditory information processing as revealed by event-related potentials and other brain measures of cognitive function. Behavioral and Brain Sciences 13, 201–288.CrossRefGoogle Scholar
Näätänen, R (1995). The mismatch negativity: a powerful tool for cognitive neuroscience. Ear and Hearing 16, 6–18.CrossRefGoogle ScholarPubMed
Näätänen, R, Michie, PT (1979). Early selective-attention effects on the evoked potential: a critical review and reinterpretation. Biological Psychology 8, 81–136.CrossRefGoogle ScholarPubMed
Oranje, B, Aggernaes, B, Rasmussen, H, Ebdrup, BH, Glenthoj, BY (2013). P50 suppression and its neural generators in antipsychotic-naïve, first-episode schizophrenia before and after 6 months of quetiapine treatment. Schizophrenia Bulletin 39, 472–480.CrossRefGoogle ScholarPubMed
Oranje, B, Jensen, K, Wienberg, M, Glenthoj, BY (2008). Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention. International Journal of Neuropsychopharmacology 11, 453–463.CrossRefGoogle ScholarPubMed
Oranje, B, van Berckel, BNM, Kemner, C, van Ree, JM, Kahn, RS, Verbaten, MN (2000). The effects of a sub-anaesthetic dose of ketamine on human selective attention. Neuropsychopharmacology 22, 293–302.CrossRefGoogle ScholarPubMed
Park, EJ, Han, SI, Jeon, YW (2010). Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: a pilot study. Progress in Neuro-psychopharmacology and Biological Psychiatry 34, 674–680.CrossRefGoogle ScholarPubMed
Polich, J, Criado, JR (2006). Neuropsychology and neuropharmacology of P3a and P3b. International Journal of Psychophysiology 60, 172–185.CrossRefGoogle ScholarPubMed
Rasmussen, H, Ebdrup, BH, Erritzoe, D, Aggernaes, B, Oranje, B, Kalbitzer, J, Pinborg, LH, Baaré, WF, Svarer, C, Lublin, H, Knudsen, GM, Glenthoj, B (2011). Serotonin 2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine. Psychopharmacology 213, 583–592.CrossRefGoogle ScholarPubMed
Rasmussen, H, Erritzoe, D, Andersen, R, Ebdrup, BH, Aggernaes, B, Oranje, B, Kalbitzer, J, Madsen, J, Pinborg, LH, Baaré, W, Svarer, C, Lublin, H, Knudsen, GM, Glenthoj, B (2010). Decreased frontal serotonin 2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia. Archives of General Psychiatry 67, 9–16.CrossRefGoogle ScholarPubMed
Rosburg, T, Boutros, NN, Ford, JM (2008). Reduced auditory evoked potential component N100 in schizophrenia – a critical review. Psychiatry Research 161, 259–274.CrossRefGoogle ScholarPubMed
Solís-Vivanco, R, Mondragón-Maya, A, León-Ortiz, P, Rodríguez-Agudelo, Y, Cadenhead, KS, de la Fuente-Sandoval, C (2014). Mismatch negativity reduction in the left cortical regions in first-episode psychosis and in individuals at ultra high-risk for psychosis. Schizophrenia Research 158, 58–63.CrossRefGoogle ScholarPubMed
Todd, J, Michie, PT, Schall, U, Karayanidis, F, Yabe, H, Näätänen, R (2008). Deviant matters: duration, frequency, and intensity deviants reveal different patterns of mismatch negativity reduction in early and late schizophrenia. Biological Psychiatry 631, 58–64.CrossRefGoogle Scholar
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, 716–725.CrossRefGoogle ScholarPubMed
Umbricht, D, Koller, R, Schmid, L, Skrabo, A, Grubel, C, Huber, T, Stassen, H (2003). How specific are deficits in mismatch negativity generation to schizophrenia? Biological Psychiatry 53, 1120–1131.CrossRefGoogle ScholarPubMed
Watson, TD, Petrakis, IL, Edgecombe, J, Perrino, A, Krystal, JH, Mathalon, DH (2008). Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission. International Journal of Neuropsychopharmacology 12, 357–370.CrossRefGoogle ScholarPubMed
Wienberg, M, Glenthoj, BY, Jensen, KS, Oranje, B (2010). A single high dose of escitalopram increases mismatch negativity without affecting processing negativity or P300 amplitude in healthy volunteers. Journal of Psychopharmacology 24, 1183–1192.CrossRefGoogle ScholarPubMed
Supplementary material: File

Oranje supplementary material

Figures S1-S4 and Table S1

Download Oranje supplementary material(File)
File 250.4 KB