20-years work investigating the shine-through paradigm in the schizophrenia spectrum: what is next?

In the past 20 years, our laboratory has proved the shine-through paradigm to be a very sensitive endophenotype for schizophrenia. The shine-through paradigm is a visual backward masking task, where the target is a vertical vernier followed by a 25-element grating mask that decreases target discriminability. Behaviorally, we have shown that schizophrenia patients, schizoaffective patients, adolescents with psychosis, adolescents with first-episode psychosis, unaffected relatives of schizophrenia patients, healthy students scoring high in schizotypal traits and patients with bipolar disorder show reproducible masking impairments compared to controls (Chkonia et al., 2010, 2010b, 2012; Herzog et al., 2004; Holzer et al., 2004, 2009; Cappe et al., 2012). Neurophysiologically, masking deficits of schizophrenia patients, patients with first-episode psychosis, students scoring high in schizotypal traits and patients with bipolar disorder are reflected in decreased global field power amplitudes of the N1 component at 200 ms after target onset (Plomp et al., 2013; Favrod et al., 2017, 2018; Garobbio et al., 2021). We found evidence for a neural compensation mechanism in unaffected siblings of patients as revealed by higher N1 amplitudes than controls (da Cruz et al., 2020). Depressive patients did not show masking deficits although they showed reduced N1 amplitudes compared to controls but stronger than schizophrenia patients (Favrod et al., 2019). Genetically, one SNP of the cholinergic system correlated well with masking deficits in schizophrenia patients (Bakanidze et al., 2013). Finally, longitudinal data proved the shine-through paradigm to be a stable endophenotype (Faggella et al., in prep.). Based on these results we propose that patients in the schizophrenia spectrum suffer from a target enhancement deficit due to a general dysfunction in attention, recurrent processing and/or neuromodulation. Similarly, there are many paradigms which show clear-cut differences between patients and controls. However, to what extent does a single endophenotype tell us about schizophrenia? Parallel work has shown very low correlations between performance level in different paradigms in both controls and schizophrenia patients (Gordillo et al., 2023; Cretenoud et al., in prep.). Therefore, it seems that each paradigm taps into roughly independent aspect of schizophrenia, which in the end might neither be necessary nor sufficient for the disease. To embrace the complexity and the heterogeneity of psychiatric disorders, we propose that future studies should consider multiple features extracted from the same and different paradigms, advocating a more integrative approach.