Schizophrenia Endophenotypes: A Review of Neurophysiological, Neuropsychological, and Social Cognition Markers

Abstract

Introduction: In schizophrenia (SCZ) research, endophenotypes represent intermediate links between the polygenic architecture of the disorder and clinical phenomenology. These neurobiological markers must meet specific criteria, including heritability, state independence, and cosegregation within families. This review examines the evolution of endophenotype research, from physiological and cognitive markers to social cognition. Method: We conducted a narrative mini-review to evaluate recent evidence on the validity of neurophysiological, neuropsychological, and social-cognitive parameters as candidate endophenotypes for SCZ. Results: Ample evidence supports oculomotor, event-related potentials, and cognitive deficits as endophenotypes found consistently in probands and first-degree relatives. In social cognition, results are more heterogeneous. While Theory of Mind and emotion processing show promise as candidate endophenotypes, evidence regarding social perception and attributional bias remains inconsistent, Discussion: Current data confirm the utility of neurophysiological and neuropsychological markers as established endophenotypes. While specific social cognition components require further validation, recent investigations demonstrate greater impairments in SCZ on mentalization tasks compared to other psychiatric conditions. The integration of these markers is relevant for stratified psychiatry and treatment personalization. Furthermore, recent findings suggest a transdiagnostic role for certain endophenotypes, indicating shared neural vulnerabilities across the schizoaffective spectrum.