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

Hindawi Schizophrenia Research and Treatment Volume 2017, Article ID 7163198, 10 pages https://doi.org/10.1155/2017/7163198 Research Article Abnormal N400 Semantic Priming Effect May Reflect Psychopathological Processes in Schizophrenia: A Twin Study Anuradha Sharma,1 Heinrich Sauer,2 Holger Hill,3 Claudia Kaufmann,4 Stephan Bender,5 and Matthias Weisbrod1,6 1 Research Group Neurocognition, Department of General Psychiatry, Centre for Psychosocial Medicine, Heidelberg University, Heidelberg, Germany 2 Department of Psychiatry, University of Jena, Jena, Germany 3 Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany 4 Department of General Internal Medicine and Psychosomatics, University of Heidelberg, Heidelberg, Germany 5 Department of Child and Adolescent Psychiatry, University Hospital Cologne, Cologne, Germany 6 Department of Psychiatry and Psychotherapy, SRH Hospital Karlsbad-Langensteinbach, Karlsbad, Germany Correspondence should be addressed to Anuradha Sharma; Received 28 November 2016; Revised 22 May 2017; Accepted 13 June 2017; Published 28 August 2017 Academic Editor: Markus Jäger Copyright © 2017 Anuradha Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. 1. Introduction Language impairment is considered as one of the hallmark symptoms of schizophrenia. Abnormal semantic priming has been reported in schizophrenia patients in various studies that have used different measures and experimental paradigms [1–4]. Semantic priming refers to the facilitated processing of a target stimulus when it is preceded by a semantically related stimulus or context. Traditionally, semantic priming studies in schizophrenia have used reduction in reaction times in primed trials as an index of semantic priming (e.g., [5, 6]). However, more recently, priming studies in schizophrenia have focused on the N400 [7–10] which is a negative-going event-related potential (ERP) peaking at centroparietal scalp sites around 400 ms after the target stimuli that are not primed by the preceding context. N400 was first identified by Kutas and Hillyard as an ERP reflecting semantic association between words elicited 400 ms after the presentation of unexpected endings of sentences [11, 12] and has been researched extensively in the following years (reviewed, e.g., in [13]). Although originally observed in the context of sentences with unpredictable endings, N400 can 2 also be evoked by isolated words, for example, the target word in a lexical decision task, and the amplitude of the N400 is considerably modified by the semantic relatedness of a previously presented word (prime) [13, 14]. Targets that have been primed by the preceding context show a reduced (less negative/more positive) N400 and this reduction, called the N400 effect, has been attributed to the activation of related semantic networks by the prime leading to facilitated processing of the target [15]. Although many studies have found the N400 effect to be abnormal in schizophrenia, the question of whether these abnormalities reflect trait markers of schizophrenia or rather reflect disease-related processes is unclear. Studies that have addressed this issue in a family design [16–19] have used different paradigms to evaluate N400 abnormalities in firstdegree family members of schizophrenia patients and have reported inconsistent results. Kimble et al. (2000) [16] found the N400 effect in a sentence paradigm to be reduced in high schizotypy individuals but not in unaffected family members of schizophrenia patients. Kiang et al. (2014) [18] reported no differences between healthy controls and unaffected firstdegree relatives of schizophrenia patients for the N400 effect; Guerra et al. (2009) [17], on the other hand, found a reduced N400 effect also in unaffected first-degree family members of patients. Pfeifer et al. (2012) [19] reported an abnormal N400 effect only for the indirect semantic condition in schizophrenia patients compared to healthy controls but failed to find differences between unaffected siblings and controls. Two studies looking at effects of medication have reported only limited effects of medication on the N400 amplitude during word recognition [20] and N400 priming effect in a lexical decision task [21] in schizophrenia patients. A useful alternative approach to examine this issue is to compare monozygotic twins concordant and discordant for schizophrenia with healthy twin pairs. Unlike first-degree relatives (who share only 50% of their genetic material), monozygotic twins share 100% of their genes and differences in phenotypic traits can be attributed to differential environmental exposure and/or disease or epigenetic processes. Although different more complex models may be employed to address the question of genetic versus environmental processes, the twin study design provides enough theoretical grounding and power for qualitative modeling of these effects and has been employed widely across heritability studies (e.g., [22]). We compared the N400 effect across a group of monozygotic twin pairs concordant and discordant for schizophrenia/schizoaffective disorder and healthy control pairs as they performed a lexical decision task (other data fr (...truncated)