Neural bases of referential thinking in schizophrenia spectrum disorders and high-risk mental states: A systematic review

Background and objectives

Nowadays, schizophrenia research is moving towards the search for early signs of illness. One of the psychosis progression markers highlighted in scientific literature is referential thinking. Thus, the main objective of this work is to analyze the main forms of assessment of referential thinking, as well as the neural bases underlying this process in people with high-risk mental states and psychotic spectrum disorders.

Methods

A systematic search was carried out in three electronic databases (Web of Science, PsycInfo, and PubMed). Experimental studies with case-control designs were searched, and then analyzed both bibliographically and based on their potential risk of bias through the Newcastle-Ottawa scale. The protocol was registered in PROSPERO [CRD42021291691].

Results

Of the 200 potentially relevant studies, 28 met the inclusion criteria. The results showed that the most common way of assessment was the experimental task of making self-reflection about personality phrases and traits. In the studies reviewed, there was a greater number of negative self-references and a greater response latency among the patients when compared to controls. Regarding neural bases, patients showed more neural activity associated with referential thinking in areas such as the dorsomedial and ventromedial prefrontal cortices, the anterior and posterior cingulate cortices, or the precuneus.

Conclusions

The results confirm the hypothesis of referential thinking as an indicator of progression in the psychotic continuum, while highlighting a set of areas that could be hyperactivated in a network of postero-anterior functional connectivity. This antero-posterior hub could underlie the referential thinking deficit in neuropsychiatric disorders.