Sex Differences in the Functional Network Underpinnings of Psychotic-like Experiences in Children

Psychotic-like experiences (PLEs) include a range of sub-threshold symptoms that resemble aspects of psychosis but do not necessarily indicate the presence of psychiatric illness. These experiences are highly prevalent in youth and are associated with developmental disruptions across social, academic, and emotional domains. While not all youth who report PLEs develop psychosis, many develop other psychiatric illnesses during adolescence and adulthood. As such, PLEs are theorized to represent early markers of poor mental health. Here, we characterized the similarities and differences in the neurobiological underpinnings of childhood PLEs across the sexes using a large sample from the ABCD Study (n=5,260), revealing sex-specific associations between functional networks connectivity and PLEs. We find that although the networks associated with PLEs overlap to some extent across the sexes, there are also crucial differences. In females, PLEs are associated with dispersed cortical and non-cortical connections, whereas in males, they are primarily associated with functional connections within limbic, temporal parietal, somato/motor, and visual networks. These results suggest that early transdiagnostic markers of psychopathology may be distinct across the sexes, further emphasizing the need to consider sex in psychiatric research as well as clinical practice.