Short Summary/Abstract:

Familial-high risk (FHR), clinical high-risk (CHR), and first episode psychosis (FEP) groups are often examined to identify markers of progression toward psychotic disorders. However, it remains unclear whether this risk spectrum can be represented by continuous behavioural or neurobiological changes reflecting proximity to chronic psychosis. Using a multimodal dataset including 70 FEP, 40 CHR, 43 FHR, and 41 controls, we found that CHR and FEP showed similar levels of symptoms and functional impairment. FEP differed from the high-risk groups mainly on cognition, while CHR showed comparatively higher depression and anxiety. Cortical thickness analyses revealed that FEP exhibited reductions resembling those seen in schizophrenia, whereas CHR showed a pattern closer to 22q11.2 deletion syndrome. Across all groups, higher cortical thickness related to better cognition and functioning and lower depression and negative symptoms, but not positive symptoms. Overall, CHR and FEP demonstrated distinct phenotypes, suggesting that CHR is not purely a pre-psychotic state and highlighting cognition as a core feature of psychosis and brain health. Through Psy-ShareD, we aim to replicate these findings, particularly the anatomical pattern in CHR and the behavioural distinctions between FEP and CHR.