Abnormal N400 Semantic Priming Effect May Reflect Psychopathological Processes in Schizophrenia: A Twin Study

Abstract

Objective Activation of semantic networks is indexed by the N400 effect. We used a twin study design to investigate whether N400 effect abnormalities reflect genetic/trait liability or are related to psychopathological processes in schizophrenia. Methods We employed robust linear regression to compare N400 and behavioral priming effects across 36 monozygotic twin pairs (6 pairs concordant for schizophrenia/schizoaffective disorder, 11 discordant pairs, and 19 healthy control pairs) performing a lexical decision task. Moreover, we examined the correlation between Brief Psychiatric Rating Scale (BPRS) score and the N400 effect and the influence of medication status on this effect. Results Regression yielded a significant main effect of group on the N400 effect only in the direct priming condition (p = 0.003). Indirect condition and behavioral priming effect showed no significant effect of group. Planned contrasts with the control group as a reference group revealed that affected concordant twins had significantly reduced N400 effect compared to controls, and discordant affected twins had a statistical trend for reduced N400 effect compared to controls. The unaffected twins did not differ significantly from the controls. There was a trend for correlation between reduced N400 effect and higher BPRS scores, and the N400 effect did not differ significantly between medicated and unmedicated patients. Conclusions Reduced N400 effect may reflect disease-specific processes in schizophrenia implicating frontotemporal brain network in schizophrenia pathology.

Neurophysiology in psychosis: The quest for disease biomarkers

“…Previous studies have consistently found that patients with psychosis showed reduced N400 amplitude to semantically incongruent words compared to controls, as well as smaller priming effects (difference between N400 amplitude to congruent and incongruent words) [119,120]. Similar deficits in N400 were also found in individuals at clinical high risk [121], but not in unaffected relatives of patients [122,123], indicating that N400 might be a state marker for psychosis instead of an endophenotype of genetic predisposition.…”

N400 event‐related brain potential as an index of real‐world and neurocognitive function in patients at clinical high risk for schizophrenia

“…For instance, antipsychotic treatment is associated with improvement in N400 semantic priming deficits in patients with schizophrenia (Besche-Richard, Iakimova, Hardy-Bayle, & Passerieux, 2014;Condray et al, 2003;Condray, Steinhauer, Cohen, van Kammen, & Kasparek, 1999;Goldberg, Dodge, Aloia, Egan, & Weinberger, 2000). Moreover, N400 semantic priming effects were found to be normal in schizophrenia patients' first-degree relatives, including monozygotic twins (Kiang et al, 2014;Sharma et al, 2017), providing convergent evidence that N400 priming deficits are a biomarker of the psychotic state itself rather than of genetic risk for developing schizophrenia.…”

Disembodied Language in Early-Onset Schizophrenia

“…A major confounding factor is the use of word semantics during the task. Presented deficits may not reflect spatial (somatic) representation of words, but aberrant semantic networks are evidenced for patients with psychosis ( 36 ) and semantic priming effect ( 37 ). This effect enables faster decision-making due to presentation with context information, hence in our study, preceding words could induce choosing the other one as the next in the procedure of placing.…”