Atypical semantic priming in individuals at clinical risk for psychosis

Schizophr Res. 2026 May 16:295:3-10. doi: 10.1016/j.schres.2026.05.002. Online ahead of print.

Abstract

Background: Loosening of the associative connections between words and concepts is a core feature of psychotic disorders and is consistently related to disrupted semantic processing and impairments in real-world functioning. Both behavioral and neural indices of altered semantic processing have been studied in psychotic disorders but are underexplored in clinical high-risk (CHR) individuals.

Methods: We analyzed behavioral responses and EEG from 73 participants (CHR = 35 [female = 19], HC = 38 [female = 24]) completing the N400 Word Pair Judgement Task. In each trial, participants viewed a prime word followed by a target word and judged whether the pair was semantically related or unrelated.

Results: Behaviorally, the CHR group exhibited disrupted unrelated-related semantic priming (t(63.22) = 2.84, p = .006). Neurophysiologically, CHR had slightly smaller N400 semantic priming effects on average, but this difference was not significant (t(60.0) = 0.84, p = .40). Reduced N400 semantic priming effects were related to greater disorganization symptoms, specifically bizarre thinking (r(66) = 0.26, p = .035). Furthermore, smaller N400 semantic priming effects predicted lower Global Functioning: Social Scale (r(70) = -0.35, p = .002) and Global Functioning: Role Scale (r(70) = -0.33, p = .003).

Discussion: While we observed disrupted behavioral semantic priming in CHR, we did not replicate previously observed group differences in N400 semantic priming. Associations between N400 and bizarre thinking are consistent with disrupted semantic processing, driving associative loosening. Moreover, associations between N400 and global social/role functioning suggest that atypical semantic processing may contribute to downstream impairments in real-world functioning.

Keywords: Associative Loosening; Disorganization; EEG; ERP; Functioning; N400.