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Background and Hypothesis

Psychotic disorders are increasingly recognized as the extreme end of a broader psychiatric continuum, with less afflicted stages including the non-help-seeking familial high-risk state (FHR), the help-seeking clinical high-risk state (CHR), and first episode psychosis (FEP). However, we lack comprehensive analyses which capture the diversity of clinical, cognitive, functional, and neuroanatomical markers across all three psychosis risk groups, limiting our understanding of how the multimodal phenotypes which define psychotic disorders vary in the broader scope of psychopathology.

Study Design

We leveraged a sample of 70 FEP, 40 CHR, 43 FHR, and 41 healthy participants recruited from the same clinical and sociodemographic setting, profiled with a dense multimodal battery.

Study Results

Treating our clinical dataset as a multidimensional spectrum, we saw that CHR expressed the most depression-anxiety symptoms, while FEP endorsed the most negative-cognitive-functioning abnormalities, though groups largely overlapped along these dimensions at the individual level. From a neuroimaging perspective, FEP was the only group to show cortical thickness reductions resembling those seen in schizophrenia, while no consistent anatomical pattern could be identified in CHR across our sample or two international replication cohorts. The dominant axis of brain-behaviour covariance captured a relationship between reduced cortical thickness and elevated negative and cognitive symptoms, a pattern seen equivalently in both CHR and FEP. Across groups, negative and cognitive symptoms also trended towards predicting lower functioning at 6-month follow-up.

Conclusions

Our analysis suggests that CHR and FEP are characterized by marked phenotypic overlap, favouring transdiagnostic staging models which tailor care to each individual’s unique symptom profile.