Structural and Functional Neural Correlates of Schizotypy: A Systematic Review

Public Significance Statement This systematic review indicates that schizotypy is associated with structural and functional changes in frontal and temporal brain regions, extending to several additional regions. Schizotypy refers to a multidimensional construct that spans a range of cognitive, behavioral, and personality features, representing liability to psychosis on a continuum between health and illness. Schizotypy has been associated with functional and structural brain alterations as potential intermediate phenotypes on the developmental path to psychosis. We scanned the literature between February 2019 and August 1, 2020 using PubMed, Medline, APA PsycINFO, and ProQuest. We identified eligible articles conducted on participants assessed with psychometric schizotypy across the health-illness spectrum and reporting a direct statistic between schizotypy and a structural, task-related, or functional magnetic resonance imaging brain measure. Articles not peer-reviewed and not written in English were excluded. We systematically reviewed 84 studies that determined the changes in gray matter, brain activation, and connectivity associated with schizotypy in both healthy and clinical cohorts. Morphological and functional changes in the default and the frontoparietal networks, specifically frontal and temporal cortices, were most frequently associated with schizotypy. Yet, we were unable to identify consistent patterns of morphological or functional brain aberration associated with schizotypy, due to methodological differences between studies in the conceptualization and measurement of schizotypy. Efforts toward greater methodological concordance in future neuroimaging research of schizotypy are needed to improve the identification of brain-based endophenotypes for schizophrenia.

Automated summary

This systematic review explores the association between schizotypy and structural and functional brain changes, suggesting schizotypy may be a potential intermediate phenotype in the developmental path to psychosis. The study found that schizotypy is related to changes in gray matter, brain activation, and connectivity, particularly in the default mode and frontoparietal networks. However, due to methodological differences, consistent patterns of brain aberration associated with schizotypy were not identified, highlighting the need for greater methodological concordance in future neuroimaging research.