N400 event‐related brain potential and functional outcome in persons at clinical high risk for psychosis: A longitudinal study

Abstract

Background: The N400 event-related brain potential (ERP) semantic priming effect is thought to reflect activation by meaningful stimuli of related concepts in semantic memory and has been found to be deficient in schizophrenia. We tested the hypothesis that, among individuals at clinical high risk (CHR) for psychosis, N400 semantic priming deficits predict worse symptomatic and functional outcomes after one year.Methods: We measured N400 semantic priming at baseline in CHR patients (n = 47) and healthy control participants (n = 25) who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured patients' psychosislike symptoms with the Scale of Prodromal Symptoms (SOPS) Positive subscale, and academic/occupational and social functioning with the Global Functioning (GF):Role and Social scales, respectively, at baseline and one-year followup (n = 29).Results: CHR patients exhibited less N400 semantic priming than controls across SOAs; planned contrasts indicated this difference was significant at the 750-ms but not the 300-ms SOA. In patients, reduced N400 semantic priming at the 750-ms SOA was associated with lower GF:Social scores at follow-up, and greater GF:Social decrements from baseline to follow-up. Patients' N400 semantic priming was not associated with SOPS Positive or GF:Role scores at follow-up, or change in these from baseline to follow-up. Conclusions:In CHR patients, reduced N400 semantic priming at baseline predicted worse social functioning after one year, and greater decline in social functioning over this period. Thus, the N400 may be a useful prognostic biomarker of real-world functional outcome in CHR patients.

Linguistic findings in persons with schizophrenia—a review of the current literature

“… Kuperberg, 2010a , b ; Almeida and Radanovic, 2021 ). In this context, results from N400-studies hint at a potentially important effect of the experimental setting, in that reduced N400 effects both in persons diagnosed with schizophrenia ( Wang et al, 2011 ; Mohammad and DeLisi, 2013 ) and in those at high risk ( Lepock et al, 2019 , 2022 ) were observed particularly when the interstimulus interval (SOA) was long. Since these long SOAs favor the use of controlled semantic search strategies ( Kuperberg et al, 2010 ), automatic activation could be overactive ( cf.…”

“…Studies at the levels of lexico-semantics, syntax, and pragmatics revealed findings in individuals at high risk that were comparable to those of persons with schizophrenia, and in some cases, associated with an increased risk for manifestation of psychosis. Comparable to persons with schizophrenia ( Wang et al, 2011 ; Mohammad and DeLisi, 2013 ), in persons at clinical high risk, the N400 effect in priming studies was largely intact at short SOAs but markedly diminished at long intervals ( Lepock et al, 2019 ), which was associated with a decrease in global functioning levels ( Lepock et al, 2022 ). This was interpreted in terms of intact early activation of related concepts but poor maintenance of such activation and suggested as a possible neurophysiological biomarker for schizophrenia risk ( Lepock et al, 2019 ).…”

Beyond verbal fluency in the verbal fluency task: semantic clustering as a predictor of remission in individuals at clinical high risk for psychosis

“…24,25 In CHR individuals, it has recently been suggested that altered semantic processing may be a marker of prognosis. [26][27][28] Although most of these studies focused on conversion to psychosis as a prognostic outcome, an electrophysiological study showed that the baseline N400 semantic priming effect, which is regarded as an electrophysiological marker of seman tic processing, could predict social functioning after 1 year in CHR participants. 26 The results of the present study add to the literature, confirming that altered semantic processing at baseline and its relationship with clinical outcome is evident not only at the electrophysiological level, but also at the neurocognitive performance level.…”

N400 event‐related brain potential index of semantic processing and two‐year clinical outcomes in persons at high risk for psychosis: A longitudinal study

“…The ERP procedure was conducted at baseline, and the procedure and results from this baseline assessment have been previously reported (Lepock et al, 2022). The stimuli included 80 related (e.g., METAL–STEEL) and 80 unrelated (DONKEY–PURSE) prime‐target word pairs.…”