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.

Figure 1

The lexical decision task. Prior to the trial, the computer screen was blank. A trial started with a fixation point (∗) presented for 700 ms followed by presentation of the prime for 250 ms which was immediately succeeded by the presentation of the target word. The target was displayed for 2 s, after which the screen went blank for 1.5 s.

Figure 2

Topographical maps depicting the distribution of (a) direct and (b) indirect N400 priming effect (in microvolts) across the scalp for the concordant healthy control group. The effect was centered around the medial electrode site (Cz).

Figure 3

Grand-averaged EEG waveforms at the Cz electrode depicting the course of the ERPs across the three conditions and the four monozygotic twin groups: (a) concordant healthy, (b) discordant unaffected, (c) discordant affected, and (d) concordant affected.

Figure 4

Box plot depicting the distribution of direct N400 priming effect (in microvolts) across the monozygotic twins: concordant healthy (CC healthy, N = 38), discordant unaffected (DC unaffected, N = 11), discordant affected (DC affected, N = 11), and concordant for schizophrenia/schizoaffective disorder (CC affected, N = 12).