Electrophysiological, cognitive and clinical profiles of at-risk mental state: The longitudinal Minds in Transition (MinT) study

Abstract

The onset of schizophrenia is typically preceded by a prodromal period lasting several years during which sub-threshold symptoms may be identified retrospectively. Clinical interviews are currently used to identify individuals who have an ultra-high risk (UHR) of developing a psychotic illness with a view to provision of interventions that prevent, delay or reduce severity of future mental health issues. The utility of bio-markers as an adjunct in the identification of UHR individuals is not yet established. Several event-related potential measures, especially mismatch-negativity (MMN), have been identified as potential biomarkers for schizophrenia. In this 12-month longitudinal study, demographic, clinical and neuropsychological data were acquired from 102 anti-psychotic naive UHR and 61 healthy controls, of whom 80 UHR and 58 controls provided valid EEG data during a passive auditory task at baseline. Despite widespread differences between UHR and controls on demographic, clinical and neuropsychological measures, MMN and P3a did not differ between these groups. Of 67 UHR at the 12-month follow-up, 7 (10%) had transitioned to a psychotic illness. The statistical power to detect differences between those who did or did not transition was limited by the lower than expected transition rate. ERPs did not predict transition, with trends in the opposite direction to that predicted. In exploratory analysis, the strongest predictors of transition were measures of verbal memory and subjective emotional disturbance.

Impaired mismatch negativity to frequency deviants in individuals at ultra-high risk for psychosis, and preliminary evidence for further impairment with transition to psychosis

“…Of the previous studies investigating fMMN in UHR (Atkinson et al, 2017;Bodatsch et al, 2011;Koshiyama et al, 2017;Mondragon-Maya et al, 2013;Nagai et al, 2013), to the best of our knowledge only one has shown decreased fMMN in UHR (Perez et al, 2014), consistent with the results of the present study. These studies in UHR have used either the CAARMS or the Structured Interview for Prodromal Symptoms (SIPS;Miller et al, 2002) to determine the eligibility of participants.…”

“…The present observation of a decline in fMMN around the time of transition to psychosis also supports this hypothesis. To the best of our knowledge, only one other study has looked at the longitudinal changes in the fMMN following transition to psychosis, and their results showed no change in fMMN amplitude over time (Atkinson et al, 2017). Similar to the present report, their UHR-T group constituted of six individuals and, therefore, the statistical power for both studies is low.…”

“…In regards to the question of whether fMMN is a state marker of psychosis: Salisbury et al (2007) suggested that fMMN impairment worsens with deterioration of illness in chronic schizophrenia patients. This hypothesis has only been directly tested once in UHR individuals (Atkinson et al, 2017). In this study, a relatively low proportion (10%) of UHR participants transitioned to psychosis, and no significant decline in fMMN amongst these individuals was observed.…”

“…In this study, a relatively low proportion (10%) of UHR participants transitioned to psychosis, and no significant decline in fMMN amongst these individuals was observed. Thus, the second aim of the present study was to replicate the longitudinal design of Atkinson et al (2017Atkinson et al ( ) (2017, and measure the course of fMMN amplitudes in UHR individuals who transitioned to psychosis (UHR-T) over the follow-up period, compared to those UHR individuals who did not transition to psychosis over this period (UHR-NT). Consistent with previous studies (Bodatsch et al, 2011;Brockhaus-Dumke et al, 2005;Mondragon-Maya et al, 2013;Nagai et al, 2013), it was anticipated that fMMN would not be impaired at baseline in UHR-T participants compared to UHR-NT participants, but that a between-group difference would emerge as a decline in fMMN magnitude over time in the UHT-T group, consistent with the staging model of psychosis (McGorry et al, 2013).…”

Staging model in psychiatry: Review of the evolution of electroencephalography abnormalities in major psychiatric disorders

“…Altogether, it appears that fMMN impairment worsens with deterioration of illness, and this hypothesis has been recently tested using longitudinal study designs. One study supported the hypothesis showing a significant decline in fMMN following transition (Lavoie et al, ), while the other did not (Atkinson et al, ).…”