Genetic and environmental contributions to psychotic-like experiences and working memory connectivity in Turkish adolescents and young adults : a twin study

Abstract

Psychosis lies on a continuum, with psychotic-like experiences (PLEs) observed in healthy populations to full-blown psychotic disorders such as schizophrenia. PLEs are relatively common during adolescence, with distress associated with these experiences playing an essential role in determining their clinical significance. Adolescence is a critical time period where the brain undergoes substantial functional reorganization and where psychotic disorders first manifest. One promising intermediate phenotype for psychosis is the working memory with both patients, their first-degree relatives showing disruptions in performance and functional connectivity (FC). The overall aim of this thesis was to investigate the relationship between PLEs and FC mechanisms. The first study investigated the relationship between PLEs and task-based FC during a working memory task in adolescents. Moreover, we aimed to decompose the genetic and environmental influences in PLEs and FC measures via twin modeling. Our findings revealed that altered connectivity in the inferior frontal gyrus was associated with in- creased frequency and distress of PLEs during adolescence. Importantly, distress associated with PLEs showed moderate heritability, while the frequency of PLEs was predominantly shaped by environmental factors. The FC measures were mainly influenced by unique environmental factors, highlighting the critical role of environmental exposures during adolescence. The second study investigated COVID-19 as an environmental risk factor for psychosis and examined the differences in FC between COVID-19 patients and healthy controls. Further, the effect of the frequency of PLEs and the inflammation markers on functional connectivity differences was studied. The results demonstrated that while COVID-19 patients showed hypoconnectivity in the sensorimotor, central executive, and language networks, they showed hyperconnectivity in the visual network compared to healthy controls. Furthermore, including positive PLEs as a covariate revealed that the COVID-19 group exhibited greater functional connectivity within the salience and central executive networks. The findings of this thesis highlight the importance of environmental risk factors that increase psychosis risk by altering the underlying functional brain mechanisms.