Duration and Frequency Mismatch Negativity in Schizophrenia, Unaffected first-degree relatives, and Healthy controls

BackgroundMismatch negativity (MMN) is elicited upon detecting background irregularities in the sensory environment and subsequent updating of the sensory context. Auditory MMN amplitude is reliably attenuated in schizophrenia patients. However, due to diversity in MMN deviant types (duration, frequency, intensity, gap, etc.), considerable variability exists in MMN findings reported from the early course and chronic samples. MMN is sometimes reported to be impaired or associated with schizotypy, but MMN and schizotypy are yet to be well examined in unaffected first-degree relatives of schizophrenia patients. MethodsFifty-two schizophrenia patients (SZ) were compared with thirty-six unaffected first-degree relatives (FDR) of schizophrenia patients and thirty-two age and sex-matched healthy controls (HC) on MMN indices using a two-tone passive auditory oddball paradigm with two conditions - duration deviant (MMNd) and frequency deviant (MMNf) event-related potential experiment. SZ sample was further split into two sub-groups 1) early-course/drug-naive or drug-free (dSZ), and 2) chronic/medicated (cSZ) to examine the effect of illness chronicity and medication on MMN indices. We also checked whether schizotypy scores associated with MMNd and MMNf amplitudes in the FDR group. ResultsAt baseline, SZ group had significantly diminished MMNd amplitude compared to both HC and FDR groups (p<0.001). The SZ group also had significantly lower MMNd latency than the FDR group (p<0.014). The cSZ and dSZ groups did not differ from each other on MMN amplitude or latency, though cSZ group had lower MMN amplitude. Only cSZ patients showed negative correlation of MMNd amplitude with hallucinations scores and total duration of illness. In FDRs, MMNd and MMNf amplitudes showed negative correlation with the cognitive-perceptual factor of schizotypy. DiscussionDeficient MMNd in SZ patients adds further support to the prediction error estimation abnormalities in schizophrenia. MMNd is a more robust measure than MMNf in differentiating SZ from FDR and HC. MMNd amplitude could be more impaired in hallucinating SZ patients and associate with illness chronicity. Though unaffected FDRs have MMN comparable to healthy controls, higher schizotypy in FDR is associated with lower MMN amplitude. MMN and schizotypy are potentially linked and deserve a nuanced examination.