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 c ... mehrompared 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 effectmay reflect disease-specific processes in schizophrenia implicating frontotemporal brain network in schizophrenia pathology.