Les résultats des évaluations cliniques et cognitives que nous avons présentés dans ce travail de thèse apportent des arguments en faveur de l’hypothèse d’un continuum développemental autisme-schizophrénie. Nous avons tout d’abord confirmé, avec deux outils différents (le MASC et l’épreuve des Triangles Animés), l’existence d’un déficit de cognition sociale chez de jeunes adultes avec schizophrénie ou avec autisme sans déficience intellectuelle. L’altération globale des capacités de mentalisation, évaluées par le MASC, apparaît plus importante dans l’autisme que dans la schizophrénie. Dans les deux troubles, cette altération était au moins en partie sous tendue par un hypo-mentalisation, c’est à dire un défaut ou une absence d’attribution d’état mentaux. Nous avons également mis en évidence une dimension transnosographique de désorganisation de la pensée et du langage, qui s’avère en outre corrélée à la charge neuro-développementale révélée par les signes neurologiques mineurs, ainsi qu’à l’importance de l’atteinte de la cognition sociale. Dans la schizophrénie, l’épreuve des Triangles Animés a mis en évidence une tendance à hypermentaliser. L’hypermentalisation est probablement elle–même un processus hétérogène. En l’occurrence, nos travaux révèlent non pas une attribution excessive, mais une perception infondée d’états mentaux. Chez ces sujets, l’atteinte de la cognition sociale est aussi corrélée au niveau de désorganisation de la pensée et du langage et de signes neurologiques mineurs, mais pas aux dimensions de symptômes positifs ou négatifs. Au total, l’apport de l’étude concomitante de la cognition sociale et de marqueurs neuro-développementaux apparaît indéniable. Les processus de perception et d’attribution d’état mentaux sont cependant complexes. Une évaluation plus exhaustive semble donc nécessaire, par le couplage à l’eye-tracking et l’utilisation de plusieurs épreuves (permettant non seulement d’en appréhender chaque composante mais aussi de distinguer hypo- et hypermentalisation).
A l’interface entre autisme et schizophrénie se dessine un sous-groupe de sujets avec schizophrénie dont les prodromes sont apparus précocement, à forte charge neurodéveloppementale, se distinguant par une désorganisation et une altération de la cognition sociale plus marqués. La littérature et nos résultats préliminaires suggèrent que les déviations du développement dans la trajectoire précoce, et en particulier les signes autistiques, sont plus importants dans cette population. L’étude de ce sous-groupe permettra
d’avancer dans la compréhension des mécanismes pathologiques à l’œuvre dans la schizophrénie. En ce sens et à l’avenir, les données issues du phénotypage clinique et cognitif avancé proposé dans le protocole AUSZ seront confrontées aux données issues de l’imagerie cérébrale en IRM et génétique disponibles pour les 145 participants de cette étude, aussi bien à travers l’étude des corrélats que par l’application d’algorithme de machine-learning.
Sur le plan clinique, le diagnostic différentiel entre autisme et schizophrénie peut s’avérer difficile. Les outils diagnostiques à disposition sont peu utilisable en pratique courante, et peu adaptés à une population adulte. A travers nos travaux, nous avons contribué à valider la version française d’une épreuve originale, mixte et écologique de la cognition sociale (le MASC). Le travail de validation d’un questionnaire de dépistage rétrospectif des troubles du développement et des signes d’autisme précédemment développé par notre équipe (le DTD) est en cours. La construction d’une évaluation standardisée intégrant ces deux outils et associée à l’examen des signes neurologiques mineurs, relativement peu coûteuse en temps de formation et de passation, et ne nécessitant pas impérativement la présence des parents, serait utile pour étayer cette réflexion diagnostique. Chez les personnes souffrant de schizophrénie, au delà de la question nosographique, la mise en évidence de signes d’autisme dans l’enfance ou d’altérations de la cognition sociale participera à la construction d’un projet de soins personnalisé reposant sur une prise en charge spécifique de ces dimensions. La réflexion thérapeutique devra ainsi tenir compte de la susceptibilité individuelle aux effets secondaires neurologiques des antipsychotiques, non seulement en terme de choix de molécule, mais aussi de posologie. En complément du traitement médicamenteux, un accompagnement en thérapie cognitive et comportementale ou en remédiation cognitive, ciblant entre autre les habiletés sociales et les processus de mentalisation paraît incontournable. Enfin, dans la perspective de développer des interventions préventives, des travaux prospectifs doivent être engagés afin de mieux connaître et comprendre les trajectoires évolutives lorsque des déviations développementales sont repérées précocement.
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