Psychotic-like experiences and working memory connectivity in adolescents and young adults: A study on Turkish twins

Objective: Psychotic-like experiences (PLEs) are common during adolescence, with distress playing a key role in their clinical significance. Working memory (WM) deficit is an endophenotype for psychosis that may also be present in individuals with PLEs. The neural mechanisms underlying PLEs remain underexplored, particularly in non-western non-European populations. We hypothesized that altered frontal connectivity during a WM fMRI paradigm would be associated with PLEs and that twin modeling would reveal both genetic and environmental factors as contributing to these traits. Methods: 474 Turkish adolescent and young adult twins and siblings (aged 14-23) underwent fMRI, clinical, and additional evaluations. Seed-based connectivity analysis was conducted using 11 predefined prefrontal regions, given their role in WM and psychosis, during the manipulation condition. These connectivity variables were then used as predictors in linear mixed models of PLE frequency and distress. Additionally, twin modeling was conducted to quantify the genetic and environmental contributions to these traits. Results: Altered connectivity in the inferior frontal gyrus was associated with increased frequency and distress of PLEs. Twin models revealed moderate heritability for PLE distress, whereas PLE frequency and WM connectivity during fMRI showed environmental influences. Bivariate twin models suggested no significant genetic or environmental covariance between PLEs and frontal connectivity. Conclusion: Our findings emphasize the importance of distinguishing between the distress and frequency of PLEs, as they may have different underlying influences. These results highlight the role of environmental exposures in shaping PLEs and frontal connectivity during adolescence, paralleling findings on schizophrenia.