Reduced activation of the ventromedial prefrontal cortex during self-referential processing in individuals at ultra-high risk for psychosis

Objective: Defects in self-referential processing and perspective-taking are core characteristics that may underlie psychotic symptoms and impaired social cognition in schizophrenia. Here, we investigated the neural correlates of self-referential processing regardless of the perspective taken and third-person perspective-taking regardless of the target person to judge relevance in individuals at ultra-high risk for psychosis. We also explored relationships between alterations in neural activity and neurocognitive function and basic self ('ipseity') disorder. Methods: Twenty-two ultra-high-risk individuals and 28 healthy controls completed a functional magnetic resonance imaging task. While being scanned, participants were asked to take a first-person perspective or to put themselves in their close relative's place thereby adopting a third-person perspective during judgments of the relevance of personality trait adjectives to one's self and a close relative. Results: For self-referential (vs other-referential) processing, ultra-high-risk individuals showed less neural activity in the left ventromedial prefrontal cortex/medial orbitofrontal cortex, which was correlated with poor working memory performance. When taking a third-person perspective (vs first-person perspective), ultra-high-risk individuals showed more activity in the middle occipital gyrus. Conclusion: Taken together, our findings suggest that ultra-high-risk individuals already show aberrant neural activity during self-referential processing which may possibly be related to engagement of working memory resources.