Trait, staging, and state markers of psychosis based on functional alteration of salience-related networks in the high-risk, first episode, and chronic stages

Objective: Salience is a critical mechanism for survival in animals, the alteration of which is postulated to play key role in psychosis, including the hippocampus-midbrain-striatal and anterior cingulate cortex (ACC)-insular (salience network: SN) systems. However, how these two systems contribute to the psychosis traits, staging, and state is unknown. Methods: Eight scanners at seven sites recruited 29 ultra-high-risk (UHR) individuals and 25 matched healthy controls (HC), 81 first-episode psychosis (FEP) patients and 109 HC, and 99 chronic psychosis (ChrP) patients and 145 HC. Resting-state functional MRI data which were intensively denoised and site effect-removed revealed the two systems as comprising five networks: the medial temporal lobe network (MTLN), midbrain-thalamic and striatal parts of the basal ganglia network (BGN-MbThal and BGN-Str), and ACC and insular parts of the SN (SN-ACC and SN-Ins). Group difference and correlation with positive symptom of network measures were performed in each psychosis stage. Results: Connectivity within the BGN-MbThal was reduced in FEP compared to HC (p FEP>ChrP. FEP showed increased brain-state instability among the five networks, and positive correlation between positive symptom and connectivity within and between the MTLN. The correlation was stronger in unmedicated than medicated, and in affective than non-affective psychosis patients (all p<0.05, FWE). Conclusions: Two salience-related systems were associated with psychosis traits, staging, and state. Refining these findings will lead to the development of clinically usable biomarkers.