Event-related brain potential study of semantic priming in unaffected first-degree relatives of schizophrenia patients

Schizophrenia is associated with abnormalities in using meaningful stimuli to activate or prime related concepts in semantic long-term memory. A neurophysiological index of this activation is the N400, an event-related brain potential (ERP) waveform elicited by meaningful stimuli, which is normally reduced (made less negative) by relatedness between the eliciting stimulus and preceding ones (N400 semantic priming). Schizophrenia patients exhibit N400 semantic priming deficits, suggesting impairment in using meaningful context to activate related concepts. To address whether this abnormality is a trait-like marker of liability to schizophrenia or, alternatively, a biomarker of the illness itself, we tested for its presence in schizophrenia patients' unaffected biological relatives. We recorded ERPs from 12 unaffected first-degree relatives of schizophrenia patients, 12 schizophrenia patients, and 12 normal control participants (NCPs) who viewed prime words each followed at 300- or 750-ms stimulus-onset asynchrony (SOA) by an unrelated or related target word, or a nonword, in a lexical-decision task. As expected, across SOAs, NCPs exhibited smaller (less negative) N400 amplitudes for related versus unrelated targets. The same pattern held in relatives, whose N400 amplitudes for related and unrelated targets did not differ from NCPs'. In contrast, consistent with previous results, schizophrenia patients exhibited larger N400 amplitudes than NCPs (and relatives) for related targets, such that patients' N400 amplitudes for related and unrelated targets did not differ. N400 amplitudes for unrelated targets did not differ between the three groups. Thus, N400 semantic priming deficits in a visual word-pair paradigm may be an illness biomarker for schizophrenia.