[Electrophysiology and schizophrenic vulnerability: the N400 component as endophenotype candidate?]

Abstract

Research on early stages of schizophrenia aims to provide early, objective, and stable markers of vulnerability. In this review, we first briefly describe the notion of such markers, or endophenotypes, notably in terms of stability, specificity and heritability. Among other empirical approaches, event-related potentials (ERPs) have been recently considered as putative endophenotypes. The N400 component is an event-related brain potential classically elicited during semantic processing, as suggested by a growing body of empirical studies with a large variety of paradigms. We provide here a short account of its typical descriptions and the interpretations of its functional significance. Then we describe the main current results about schizophrenic alterations of the N400 component. Two levels of semantic processing (automatic spreading and controlled mechanisms) are disturbed in schizophrenia, even if the underlying mechanisms remain unclear or discussed. Several controversial issues may also need further research, such as the influence of symptomatology and evolution of schizophrenia. Another crucial topic concerns the putative schizophrenic specificity, and only little is known about possible alterations of N400 in affective disorders. We discuss the notion of heritability, mainly explored in current literature among people with schizotypal personality. Finally, even if N400 studies contribute to a better understanding of linguistic disturbances in schizophrenia, it appears difficult to consider the N400 component as a relevant schizophrenic endophenotype, given the current paucity of results on its stability, its heritability (clinical and genetic vulnerability) and its schizophrenic specificity.