Mismatch negativity amplitude in first-degree relatives of individuals with psychotic disorders: Links with cognition and schizotypy

Abstract

Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

Keywords: Genetic risk; Mismatch negativity (MMN); Psychosis; Schizophrenia; Schizotypy.

Figure 1.

ERP Waveforms and Scalp Distributions Note. Duration mismatch negativity (MMN-D, top) and frequency mismatch negativity (MMN-F, bottom) at electrode Fz in probands with psychosis, their siblings, and never psychotic comparison subjects. MMN amplitude scored as difference wave at electrode Fz. Highlighted area represents amplitude displayed in scalp topography map (left). NP = never psychotic; ms = milliseconds; μV = microvolts.

Figure 2.

Relationships of MMN Amplitude with Cognition and Schizotypy Note. Scatterplots illustrating associations between duration mismatch negativity (MMN-D) and measures of overall cognition score (A) and schizotypal symptoms, including mistrust (B), eccentric perceptions (C), and detachment (D). Effects are illustrated across probands, siblings, and never-psychotic comparison subjects. *Indicates p<.05; **p<.01; ***p<.001.