In Search of Psychosis Biomarkers in High-risk Populations: Is the Mismatch Negativity the One We've Been Waiting for?

Abstract

In this issue of Biological Psychiatry, Atkinson et al. ( 1 Atkinson R.J. Michie P.T. Schall U. Duration mismatch negativity and P3a in first-episode psychosis and individuals at ultra-high risk of psychosis. Biol Psychiatry. 2012; 71: 98-104 Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar ) describe alterations in early preattentive brain electrical activity in individuals meeting criteria for ultrahigh risk (UHR) for the development of psychosis. Identifying biological markers in high-risk populations is a critical step toward informing about the pathophysiology of the disorder, predicting onset of psychosis, and potentially devising early interventions to change the course of the illness. The auditory mismatch negativity (MMN) described by Atkinson et al. is an electrical brain response that is elicited by any discriminable change in the regularity of the acoustical auditory environment. It is hypothesized to represent the initial processing step in a biologically important series of cognitive and brain events involved in alerting and redirecting the organism's attention toward novel, potentially significant, auditory stimuli in the environment. The MMN may be followed by a positive component, the P3a, which is associated with the involuntary switching of attention to salient information in the environment. Although MMN is generally considered automatic and thereby independent of primary task, some have studies have demonstrated that the complexity of a primary task can modulate the amplitude of the MMN ( 2 Yucel G. Petty C. McCarthy G. Belger A. Graded visual attention modulates brain responses evoked by task-irrelevant auditory pitch changes. J Cogn Neurosci. 2005; 17: 1819-1828 Crossref PubMed Scopus (45) Google Scholar ). Duration Mismatch Negativity and P3a in First-Episode Psychosis and Individuals at Ultra-High Risk of PsychosisBiological PsychiatryVol. 71Issue 2PreviewReduction in a pre-attentive measure of auditory change detection, mismatch negativity (MMN), is one of the most consistent findings in schizophrenia. Recently, our group showed a reduction in MMN to changes in the duration and intensity of background sounds in those within 5 years of illness onset, whereas reduced MMNs to changes in sound frequency were only seen in patients with longer illness duration. In this report, we examine whether reduced MMN, as well as P3a, another index of auditory deviance detection, to duration changes is evident even earlier in the illness, that is, in individuals in the first episode of a psychosis (FEP) and individuals identified as being at ultra-high risk of developing schizophrenia (UHR). Full-Text PDF