Endophénotypes neurophysiologiques et trouble schizophrénique : naissance et évolution d'un concept clinique

It is proposed an historical approach to concepts leading to the development of operational paradigms for measuring objectives neurophysiological endophenotypes. It is hypothesized that psychiatric interest for paradigms measuring Event-Related Potential (ERP) come from Bleuler (1911) and McGhie and Chapman (1961) phenomenological and clinical descriptions. They noted, first that patients with schizophrenia generally feel as if they are being flooded by an overwhelming mass of sensory input combined with a heightened sensory perception, second that they were distractible to irrelevant sensory stimuli. These subjective abnormalities may be related, first to inability to filter incongruent information measured in a double click paradigm by a deficit in P50 amplitude gating, and second to an inability to select a stimulus of interest measured in the oddball paradigm by a deficit in P300 amplitude. The analysis of these P50 and P300 ERP in cohorts of patients with schizophrenia found most of Gottesman endophenotype criteria. P50 and P300 ERP are therefore relevant neurophysiological endophenotypes. However, from a clinical point of view, these endophenotypes lack specificity. The hypothesis of this article leads us to formulate ways of research. It is shown the value of combining objective neurophysiological measures with subjective measures using self-administered questionnaires (“offline”) or psychophysiological tests (“online”) to develop rigorous neurophysiological experimental paradigms especially as clinical observations of their origins are not forgotten.