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Background and Hypothesis

Psychotic disorders are thought to capture the extreme end of a psychiatric continuum, with less afflicted populations 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 capturing the diversity of clinical, cognitive, functional, and neuroanatomical aberrations across all three groups, limiting our understanding of how psychosis-linked phenotypes 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 catchment area, profiled with a cross-sectional and longitudinal multimodal battery.

Study Results

Using an exploratory factor analysis to treat our clinical dataset as a multidimensional spectrum, we saw that CHR expressed the most depression/anxiety symptoms, FEP endorsed the most negative/cognitive/functioning abnormalities, and FHR were comparatively less afflicted, though FEP and CHR tended to overlap along dimensions at the individual level. Regarding neuroimaging, FEP showed cortical thickness reductions resembling those seen in schizophrenia and bipolar disorder, while no consistent anatomical pattern could be identified in FHR and CHR (including in two international CHR replication cohorts). The dominant axis of brain-behaviour covariance revealed by a partial least squares correlation linked reduced cortical thickness to elevated negative and cognitive symptoms, a pattern seen most prominently in FEP. Across groups, negative and cognitive symptoms predicted lower functioning at follow-up.

Conclusions

CHR and FEP were defined by distinct yet overlapping clinical profiles, while neuroanatomical and joint clinical-neuroanatomical abnormalities were primarily seen in FEP.