Distinct and opposite profiles of connectivity during self-reference task and rest in youth at clinical high risk for psychosis

Self-reference is impaired in psychotic disorders such as schizophrenia, associated with disability, and closely related to characteristic patterns of aberrant brain connectivity. However, at present, it is unclear whether self-reference is impacted in pathogenesis of the disorder. Alterations in connectivity during a self-reference task or resting-state in the psychosis risk (i.e., prodromal) period may yield important clues for biomarker development, as well as for novel treatment targets. This study examined a task-based and resting-state functional magnetic resonance imaging in individuals at clinical high risk (CHR) for psychosis (n = 22) and healthy control unaffected peers (n = 20). The self-reference task comprised three task conditions where subjects were asked if an adjective was relevant to themselves (self), a designated other individual (other), or to evaluate the word's spelling (letter). Connectivity analyses examined medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), regions commonly found in conjunction analyses of self-reference, during both the self-reference task and rest. In task connectivity analyses, CHR individuals exhibited decreased mPFC–PCC connectivity when compared to controls. In resting-state analyses, CHR participants showed greater mPFC–PCC connectivity. Taken together, results suggest that psychosis-like alterations in mPFC–PCC connectivity is present prior to psychosis onset across both task and rest.