Altered functional connectivity in psychotic disorder not otherwise specified

•Little research has examined clinical characteristics and brain imaging markers for psychotic disorder not otherwise specified (PNOS).•We found common brain connectomics in PNOS and schizophrenia (SZ) including thalamo– cortical hyperconnectivity, thalamo–cerebellar hypoconnectivity, and reduced within-thalamic connectivity compared to HC.•Distinct features differentiating two patient groups were hyperconnectivity between the thalamic subregion and anterior cingulate cortex in PNOS compared to SZ and hyperconnectivity of the thalamic subregions with the posterior cingulate cortex and precentral gyrus in SZ compared to PNOS.•Our results support the hypothesis that PNOS should be treated as a separate clinical syndrome with distinct neural connectomics. : Few studies have investigated functional connectivity (FC) in patients with psychotic disorder not otherwise specified (PNOS). We sought to identify distinct FC differentiating PNOS from schizophrenia (SZ). : In total, 49 patients with PNOS, 42 with SZ, and 55 healthy controls (HC) matched for age, sex, and education underwent functional magnetic resonance imaging (fMRI) brain scans and clinical evaluation. Using six functional networks consisting of 40 regions of interest (ROIs), we conducted ROI to ROI and intra- and inter-network FC analyses using resting-state fMRI (rs-fMRI) data. Correlations of altered FC with symptomatology were explored. : We found common brain connectomics in PNOS and SZ including thalamo–cortical (especially superior temporal gyrus) hyperconnectivity, thalamo–cerebellar hypoconnectivity, and reduced within-thalamic connectivity compared to HC. Additionally, features differentiating the two patient groups included hyperconnectivity between the thalamic subregion and anterior cingulate cortex in PNOS compared to SZ and hyperconnectivity of the thalamic subregions with the posterior cingulate cortex and precentral gyrus in SZ compared to PNOS. : These findings suggest that PNOS and SZ exhibit both common and differentiating changes in neuronal connectivity. Furthermore, they may support the hypothesis that PNOS should be treated as a separate clinical syndrome with distinct neural connectomics.