Effect of Aripiprazole on Mismatch Negativity (MMN) in Schizophrenia

Abstract

BackgroundCognitive deficits are considered core symptoms of the schizophrenia. Cognitive function has been found to be a better predictor of functional outcome than symptom levels. Changed mismatch negativity (MMN) reflects abnormalities of early auditory processing in schizophrenia. Up to now, no studies for the effects of aripiprazole on MMN in schizophrenia have been reported.Methodology/Principal FindingsSubjects included 26 patients with schizophrenia, and 26 controls. Psychopathology was rated in patients with the Positive and Negative Syndrome Scale (PANSS) at baseline, after 4- and 8-week treatments with aripiprazole. Auditory stimuli for ERP consisted of 100 millisecond/1000 Hz standards, intermixed with 100 millisecond/1500 Hz frequency deviants and 250 millisecond/1000 Hz duration deviants. EEG was recorded at Fz. BESA 5.1.8 was used to perform data analysis. MMN waveforms were obtained by subtracting waveforms elicited by standards from waveforms elicited by frequency- or duration-deviant stimuli. Aripiprazole decreased all PANSS. Patients showed smaller mean amplitudes of frequency and duration MMN at baseline than did controls. A repeated measure ANOVA with sessions (i.e., baseline, 4- and 8-week treatments) and MMN type (frequency vs. duration) as within-subject factors revealed no significant MMN type or MMN type × session main effect for MMN amplitudes. Session main effect was significant. LSD tests demonstrated significant differences between MMN amplitudes at 8 weeks and those at both baseline and 4 weeks. There was significant negative correlation between changes in amplitudes of frequency and duration MMN and changes in PANSS total scores at baseline and follow-up periods.ConclusionsAripiprazole improved the amplitudes of MMN. MMN offers objective evidence that treatment with the aripiprazole may ameliorate preattentive deficits in schizophrenia.

Paying attention to MMN in schizophrenia

“…There is considerable 1 The reduction in MMN amplitude is assumed to be independent of psychotic state based on observations that it rarely correlates with symptoms and remains smaller than MMN in controls even when clinical symptoms improve (for review, see Umbricht and Krjles, 2000). Of note a recent study by Zhou et al (2013) found that Aripiprazole increased MMN size and reduced psychosis symptoms, however post treatment MMN remained significantly smaller than that in healthy controls. evidence that this change in responsiveness is more than just passive neural adaptation (Friston, 2005;Kiebel et al, 2008;Näätänen et al, 2005;Winkler, 2007).…”

“…(Cornblatt et al, 1989;Cornblatt and Keilp, 1994;Fisher et al, 1994;Nuechterlein et al, 1994), not remediated by psychotropic medication (Catts et al, 1995;Nielsen et al, 2012;Schall et al, 1998;Shinozaki et al, 2002;Umbricht et al, 1998;Umbricht et al, 1999;cf. Lavoie et al, 2008;Zhou et al, 2013), and has been observed in clinical high-risk individuals (Bodatsch et al, 2011;Nuechterlein, 1983;Pflueger et al, 2007) and equivocally in asymptomatic first-degree relatives (Cornblatt and Keilp, 1994;Bramon et al, 2004;Jessen et al, 2001;Magno et al, 2008;Michie et al, 2002;Nuechterlein et al, 1994;Rosburg et al, 2004). Although both reduced MMN and attentional impairments are heavily studied in schizophrenia, they are typically studied independently of each other.…”

“…There is certainly good reason to suppose that the abnormalities leading to smaller MMN could be related to similarly observed cognitive impairments such as the attentional impairments reviewed here. Uncovering such relationships could not only shed light on any common factors in disruption to underlying processing, but also on where to look for functional improvements when treatments succeed in impacting MMN (e.g., Lavoie et al, 2008;Zhou et al, 2013). …”

“…It is present in the prodromal stages of the illness (Bodatsch et al, 2011;Brockhaus-Dumke et al, 2005 Q5 ), likely independent of psychotic state 1 Q6 (Fisher et al, 2014), not remediated by psychotropic medication (Catts et al, 1995;Schall et al, 1998;Shinozaki et al, 2002;Umbricht et al, 1998;Umbricht et al, 1999; Q7 cf. Lavoie et al, 2008;Zhou et al, 2013), and has been observed in clinical high-risk individuals that later transition to the illness (e.g., Bodatsch et al, 2011) and equivocally in asymptomatic first-degree relatives (Bramon et al, 2004;Jessen et al, 2001;Magno et al, 2008;Michie et al, 2002;Rosburg et al, 2004). Despite this, very little is known about the functional relevance of reduced MMN in persons with schizophrenia.…”

Criteria for determining whether mismatch responses exist in animal models: Focus on rodents

“…Similar to the cognitive deficits of schizophrenia, there are not many studies demonstrating that MMN reductions are well-treatedby current antipsychotic drugs [see (Todd et al, 2013;Umbricht and Krljes, 2005) for review, (Zhou et al, 2013) for a positive study], and therefore also reflect the features of the disorder that remain resistant to treatment. In addition, as a neurophysiological feature rather that a behavioural one, the MMN provides a unique opportunity for translation into rodent models.…”