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Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method.

ABSTRACT: BACKGROUND:Mismatch negativity (MMN) is a measure of pre-attentive auditory information processing related to change detection. Traditional scalp-level EEG methods consistently find attenuated MMN in patients with chronic but not first-episode schizophrenia. In the current paper, we use a source-resolved method to assess MMN and hypothesize that more subtle changes can be identified with this analysis method. METHOD:Fifty-six first-episode antipsychotic-naïve schizophrenia (FEANS) patients (31 males, 25 females, mean age 24.6) and 64 matched controls (37 males, 27 females, mean age 24.8) were assessed for duration-, frequency- and combined-type MMN and P3a as well as 4 clinical, 3 cognitive and 3 psychopathological measures. To evaluate and correlate MMN at source-level, independent component analysis (ICA) was applied to the continuous EEG data to derive equivalent current dipoles which were clustered into 19 clusters based on cortical location. RESULTS:No scalp channel group MMN or P3a amplitude differences were found. Of the localized clusters, several were in or near brain areas previously suggested to be involved in the MMN response, including frontal and anterior cingulate cortices and superior temporal and inferior frontal gyri. For duration deviants, MMN was attenuated at the right superior temporal gyrus in patients compared to healthy controls (p?=?0.01), as was P3a at the superior frontal cortex (p?=?0.01). No individual patient correlations with clinical, cognitive, or psychopathological measures survived correction for multiple comparisons. CONCLUSION:Attenuated source-localized MMN and P3a peak contributions can be identified in FEANS patients using a method based on independent component analysis (ICA). This indicates that deficits in pre-attentive auditory information processing are present at this early stage of schizophrenia and are not the result of disease chronicity or medication. This is to our knowledge the first study on FEANS patients using this more detailed method.

SUBMITTER: Randau M

PROVIDER: S-EPMC6444292 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method.

Randau M M Oranje B B Miyakoshi M M Makeig S S Fagerlund B B Glenthøj B B Bak N N

NeuroImage. Clinical 20190312

<h4>Background</h4>Mismatch negativity (MMN) is a measure of pre-attentive auditory information processing related to change detection. Traditional scalp-level EEG methods consistently find attenuated MMN in patients with chronic but not first-episode schizophrenia. In the current paper, we use a source-resolved method to assess MMN and hypothesize that more subtle changes can be identified with this analysis method.<h4>Method</h4>Fifty-six first-episode antipsychotic-naïve schizophrenia (FEANS) ...[more]

PMID: 30927608

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Project description:BackgroundEnlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia.MethodsWe obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse.ResultsWe found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia.LimitationsThis study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small.ConclusionReductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.

Project description:Mismatch negativity (MMN) is a component of the event-related potential elicited by deviant auditory stimuli. It is presumed to index pre-attentive monitoring of changes in the auditory environment. MMN amplitude is smaller in groups of individuals with schizophrenia compared to healthy controls. We compared duration-deviant MMN in 16 recent-onset and 19 chronic schizophrenia patients versus age- and sex-matched controls. Reduced frontal MMN was found in both patient groups, involved reduced hemispheric asymmetry, and was correlated with Global Assessment of Functioning (GAF) and negative symptom ratings. A cortically-constrained LORETA analysis, incorporating anatomical data from each individual's MRI, was performed to generate a current source density model of the MMN response over time. This model suggested MMN generation within a temporal, parietal and frontal network, which was right hemisphere dominant only in controls. An exploratory analysis revealed reduced CSD in patients in superior and middle temporal cortex, inferior and superior parietal cortex, precuneus, anterior cingulate, and superior and middle frontal cortex. A region of interest (ROI) analysis was performed. For the early phase of the MMN, patients had reduced bilateral temporal and parietal response and no lateralisation in frontal ROIs. For late MMN, patients had reduced bilateral parietal response and no lateralisation in temporal ROIs. In patients, correlations revealed a link between GAF and the MMN response in parietal cortex. In controls, the frontal response onset was 17 ms later than the temporal and parietal response. In patients, onset latency of the MMN response was delayed in secondary, but not primary, auditory cortex. However amplitude reductions were observed in both primary and secondary auditory cortex. These latency delays may indicate relatively intact information processing upstream of the primary auditory cortex, but impaired primary auditory cortex or cortico-cortical or thalamo-cortical communication with higher auditory cortices as a core deficit in schizophrenia.

Project description:BACKGROUND:Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. OBJECTIVES:To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. SEARCH STRATEGY:We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. SELECTION CRITERIA:Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. DATA COLLECTION AND ANALYSIS:Working independently, we critically appraised records from 681studies, of which five studies met inclusion criteria. John Rathbone from the Schizophrenia Group supported us with the data extraction. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. MAIN RESULTS:Five studies with a combined N = 998 met inclusion criteria. Four studies (N = 724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs N = 353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT N = 240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT N = 236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT N = 94, RR 0.96 CI 0.3 to 3.6). Two studies (Cole 1964; May 1976) contributed data to assessment of side effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications compared to placebo. Rappaport 1978 suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (N = 80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (N = 127, RR 1.69 CI 0.9 to 3.0). One study (May 1976) contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (N = 92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One study (Mosher 1995) contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (N = 89, MD 0.01 CI -0.6 to 0.6) and global improvement (N = 89, MD -0.03 CI -0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria. AUTHORS' CONCLUSIONS:With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia.

Dataset Information

Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method.

Publications

Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method.

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