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. 2008 Sep 1;64(5):385-91.
doi: 10.1016/j.biopsych.2008.03.019. Epub 2008 May 9.

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

Elena Magno  1 , Sherlyn Yeap, Jogin H Thakore, Hugh Garavan, Pierfilippo De Sanctis, John J Foxe
Affiliations

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

Elena Magno et al. Biol Psychiatry. .

Abstract

Background: Mismatch negativity (MMN) is a negative-going event-related potential (ERP) component that occurs in response to intermittent changes in constant auditory backgrounds. A consistent finding across a large number of studies has been impaired MMN generation in schizophrenia, which has been interpreted as evidence for fundamental deficits in automatic auditory sensory processing. The aim of this study was to investigate the extent to which dysfunction in MMN generation might represent an endophenotypic marker for schizophrenia.

Methods: We measured MMN to deviants in duration (25 msec, 1000 Hz) and deviants in pitch (50 msec, 1200 Hz) relative to standard tones (50 msec, 1000 Hz) in 45 chronic schizophrenia patients, 25 of their first-degree unaffected biological relatives, 12 first-episode patients, and 27 healthy control subjects.

Results: In line with previous work, MMN amplitudes to duration deviants (but not to pitch deviants) were significantly reduced in patients with chronic schizophrenia compared with control subjects. However, both duration and pitch MMNs were completely unaffected in the first-degree biological relatives and this was also the case for the first-episode patients. Furthermore, length of illness did not predict the extent of MMN deficit.

Conclusions: These findings suggest that the MMN deficit seen in schizophrenia patients is most likely a consequence of the disease and that MMN, at least to basic auditory feature deviants, is at best only weakly endophenotypic for schizophrenia.

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Conflict of interest statement

FINANCIAL DISCLOSURES

The authors declare that no conflict of interest, financial or otherwise, is related directly or indirectly to the submitted work.

Figures

Figure 1
Figure 1
a) Average amplitudes for the duration and frequency mismatch negativity at seven fronto-central electrode sites. Groups on the x-axis are chronic schizophrenia (Chronic S.) patients, first-episode patients (F-E S.), first-degree healthy biological relatives and healthy control subjects (including a subgroup of 12 age-matched to F-E S.). b) MMN amplitudes at the left (LM) and right (RM) mastoids are plotted illustrating the characteristic polarity inversion of the MMN (i.e. positive values). For illustration purposes, the mastoids data shown were computed from average-referenced data. Amplitudes are in microvolts (µV). Error bars represent standard error of the mean (SEM).
Figure 2
Figure 2
Overview of duration MMN waveforms in all four groups. Data shown at seven representative frontal electrode sites were referenced to the LM. Time is in milliseconds (ms). Amplitudes are in microvolts (µV).
Figure 3
Figure 3
Overview of frequency MMN waveforms in all four groups. Data shown at seven representative frontal electrode sites were referenced to the LM. Time is in milliseconds (ms). Amplitudes are in microvolts (µV).
Figure 4
Figure 4
Scatterplots of duration and frequency mismatch negativity amplitude in relation to length of illness and age for the chronic patients group. Amplitudes are in microvolts (µV).
See this image and copyright information in PMC

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