Contributions of early cortical processing and reading ability to functional status in individuals at clinical high risk for psychosis

Abstract

Background There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. Methods The sample consisted of 34 CHR individuals and 33 healthy comparisons subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. Results CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Conclusions Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function.

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

“…This latter finding is consistent with numerous previous studies which have identified fMMN abnormalities in patients with chronic schizophrenia (See meta-analysis by Umbricht and Krljes, 2005). A few studies have also observed reduced fMMN in UHR when compared to healthy controls (Carrion et al, 2015;Perez et al, 2014). In light of the evidence for fMMN abnormalities in patients with long-term psychotic disorders, combined with the preliminary evidence for fMMN deficits in UHR individuals, the first aim of the current study was to investigate whether UHR individuals also exhibit fMMN deficits relative to healthy controls.…”

Auditory dysfunction in schizophrenia: integrating clinical and basic features

“…In schizophrenia, these processes are impaired, leading to reduced sensitivity to ongoing environmental (auditory) events 10,94 . Deficits in MMN are highly interrelated to impaired functional outcome in schizophrenia, including impairments in reading 93 and educational achievement 32,167 . As opposed to behavioural measures that may be difficult to translate across species, MMN provides an objective neurophysiological measure that can be implemented in primates and/or rodents to investigate underlying neural mechanisms.…”

Neurophysiological models for new treatment development in schizophrenia: early sensory approaches

“…Among individuals showing subthreshold clinical symptoms of Sz, MMN has been found to predict the time to conversion to Sz . In addition, as in established Sz, deficits in MMN generation in patients at high clinical risk for Sz also correlate strongly with overall level of social and role function . Thus, agents capable of improving MMN deficits might be especially effective when instituted at early stages of the disorder.…”