Elsevier

Schizophrenia Research

Volume 70, Issues 2–3, 1 October 2004, Pages 303-313
Schizophrenia Research

Morphological and latency abnormalities of the mid-latency auditory evoked responses in schizophrenia: a preliminary report

https://doi.org/10.1016/j.schres.2003.12.009Get rights and content

Abstract

Introduction: Evoked potential (EP) amplitude and latency abnormalities have been extensively examined in schizophrenia. Morphological abnormalities of the mid-latency auditory evoked responses (MLAERs; P50, N100, P200), on the other hand, received very little attention. Methods: Based on a priori defined set of morphological criteria, the morphology and latency of the MLAERs were blindly compared between stable outpatients with schizophrenia (N=27) and age- and gender-matched healthy control subjects (N=22). The morphology of the MLAERs was considered abnormal if one or more of the components fell outside the expected latency range, if one or more of the components were missing, or if a later occurring component was smaller in amplitude than an earlier occurring one. Results: Of the 27 schizophrenia subjects, 20 had waveforms that were deemed atypical, while only 8 from the control group were classified as atypical (χ2=5.52, p<0.02). The latencies of the P50 and N100 components, identified based on morphology, were significantly prolonged in schizophrenia patients. Conclusions: These preliminary data suggest that morphological abnormalities of the MLAERs in schizophrenia patients are significant and should be taken into consideration when examining the MLAERs of this patient population.

Introduction

Amplitude, latency, and topography of an evoked cerebral potential (EP) are the main metrics used to examine these phenomena in health and in psychopathological conditions. While the amplitude, latency, and topography of the mid-latency auditory evoked responses (MLAERs) have been characterized in healthy and in a number of psychopathological conditions, the morphology of these components (i.e., the actual shape of the wave) is yet to be examined in depth, particularly in psychiatric populations. Latency has been shown to reflect the complexity and efficiency of the synaptic pathway mediating the response and speed of information processing. Amplitude has been shown to reflect the sum of the cerebral resources allocated to a response. The correlates of the topography and the morphology of these components have not been fully elaborated. Topographical and morphological changes are likely to reflect changes in the cerebral sources (fewer sources or abnormal sources contributing to the surface-detected signal). Given the number of cerebral regions implicated in the pathology of schizophrenia, and on the assumption that some of these regions contribute to the surface-recorded components, it was our a priori prediction that the morphology of the MLAERs would deviate from those of healthy individuals.

The MLAERs have been reported to be abnormal in a number of psychiatric disorders, but most prominently schizophrenia. As early as 1977, Buchsbaum used the term middle evoked response components to describe three main auditory EP components: a positive, negative, positive sequence occurring at 50–100, 110–140, and 160–200 ms (Buchsbaum, 1977). Subsequently, Roth and Horvath (1980) used the term mid-latency to describe EP components occurring between 50 and 200 ms. These components characteristically decrease in amplitude with faster repetitions. It should be noted that the use of the term mid-latency in both otology and neurology literatures usually refer to components falling between the brainstem evoked responses and up to about 30 ms (Regan, 1989). These components have rarely been examined in association with psychiatric disorders and are of minimal interest, at least at the current time, to behavioral researchers. Thus, the use of the term mid-latency as proposed by Buchsbaum (1977) is much more meaningful to researchers whose interest is behavior and behavioral aberrations.

Morphological abnormalities of the MLAERs in schizophrenia patients have received minimal attention. This is most likely secondary to the fact that severe morphological changes, including the complete absence of the mid-latency complex, tend to cause investigators to exclude the recording of these subjects or make the identification of the components more problematic. To our knowledge, the actual frequency of complete absence of the MLAER components in schizophrenia patients has not been reported. Saletu and Saletu (1971) examined the shape of these evoked responses in schizophrenia patients with and without formal thought disorders as well as healthy control subjects. They reported that patients with thought disorder showed a high degree of variability in their evoked response patterns. The P50–N100 response (they called it K-complex) differed in amplitude and latency from trial to trial and eventually split. A later occurring response (P200) consisted of sometimes two or even three peaks. Patients without a formal thought disorder showed much less morphological deviations from healthy subjects who showed a remarkably high degree of consistency of the mid-latency responses. To our knowledge, there have been no published replications of these findings.

Evoked potential (EP) amplitude abnormalities in patients suffering from schizophrenia have been reported with much more consistency than latency abnormalities. Munkundan (1986), while reporting both amplitude and recovery abnormalities of the MLAERs, reported latencies that were rather similar between his unmedicated schizophrenia patients and healthy control subjects. Williams et al. (2000) similarly found no latency abnormalities in a group of medicated schizophrenia patients. Karoumi et al. (2000) provided evidence that the P200 component had prolonged latencies in siblings of schizophrenia patients, while they were unable to demonstrate latency abnormalities of any of the MLAERs.

EP components are usually identified by their polarity and latency. If a component falls outside the expected latency range the particular component may be discounted and hence not recognized. This seemingly circular reasoning may have contributed to a less than adequate recognition of latency abnormalities of the MLAERs in psychiatric conditions. Accurate identification of these components is essential for this area of research to be more fruitful. Hegerl et al. (1988) reported that the N1–P2 interpeak latency might have a direct correlation with the course of illness with a shorter interpeak latency being a predictor of poor prognosis. The P50 component has been used extensively to examine sensory gating (Adler et al., 1982, Boutros et al., 1991, Judd et al., 1992; and see Adler et al., 1999 for a review).

In order to provide data regarding the morphology of the MLAERs in schizophrenia, we conducted this retrospective preliminary study. In this study, we examined the morphology, latencies, and amplitudes of the MLAERs in a group of stable schizophrenia outpatients and age- and gender-matched healthy control subjects. This work was done as part of a larger study examining different aspects of sensory gating in schizophrenia. These data will be presented elsewhere (Boutros et al., under review, Psychiatry Res.).

Section snippets

Subjects

Twenty-seven (24 men and 3 women, mean age 47 with a range of 38–60), medicated with either olanzapine or risperidone and clinically stable, schizophrenia outpatients and 22 (21 men and one woman, mean age 47 with a range of 29–64) healthy control subjects were examined. Patients were recruited from the outpatient clinics of the VA-Connecticut Healthcare System (West Haven Campus). All schizophrenia patients were chronic with illness duration from 8 to 35 years. Healthy subjects were recruited

Results

Table 1 provides means and standard deviations of latencies and amplitudes of the P50, N100, and P200 of the two groups. There were significant differences between groups in amplitudes for the N100 and P200 measures, with schizophrenics having reduced amplitudes. For N100, the mean for the patients was 7.4±3.1 μV, and the mean for the controls was 11.3±4 μV (F(40,1)=12.3, p<0.002). For the P200, the mean for the patients was 10.8±5.1 μV, and the mean for the controls was 16.5±6.1 μV (F

Discussion

Two main findings emerge from the current preliminary study. One is the highly significant prevalence of morphological deviations in the MLAERs of schizophrenia patients as compared to healthy control subjects. The second important finding is the significant prolongation of the latencies of the P50 and N100 components when identification of these components was not constrained by latency-range criteria. In addition, our data support the well-documented findings of decreased N100 and P200

Acknowledgements

Financial support: This work was supported by the following grants: RO1 MH58784-01, RO1 MH58784-03A1, and the VA-Connecticut Healthcare System.

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