22q11.2 delesyon sendromlu hastalarda psikiyatrik fenotip üzerinde stres, FKBP5 gen metilasyonu ve immün faktörlerin etkisi

22q11.2 deletion syndrome (22q11.2DS) is a disorder that is associated with many psychiatric disorders and has been the focus of studies on copy number variations (CNV). The present study aims to investigate the lifetime stress factors and the epigenetic mechanisms of psychiatric phenotypes in individuals diagnosed with 22q11.2DS, in order to shed light on the gene-environment interaction on psychiatric phenotypes. 32 individuals (17 patients with 22q11.2DS and 15 matched controls) participated in the study. Structured clinical interview for DSM-5 (SCID-5), self-report psychopathology and stress scales, and The Stress and Distress Inventory (STRAIN) were used to evaluate psychiatric symptoms and stress levels throughout the participants' lifetime. Cognitive performance of the participants was measured with The Pennsylvania Computerized Neurocognitive Battery (PennCNB) and The Probabilistic Reward Task (PRT). For biological biomarkers, immune factors (C-Reactive Protein level, total white blood cell (WBC) count, lymphocyte, neutrophil counts, and neutrophil- lymphocyte ratio) were measured. Peripheral Blood Mononuclear Cells (PBMC) samples were used to analyze the methylation level at the cg00130530 region of FKBP5 gene using pyrosequencing method. Our results revealed that there was a high prevalence of anxiety disorders in the 22q11.2DS group. Participants with 22q11.2DS had lower performance in PennCNB (depending on the overall summary score for battery), episodic memory, and social cognition than control groups. They had also lower discriminability score but no difference in response bias in PRT task. When evaluated in terms of immune factors, only lymphocyte cell count was found to be lower in the 22q11.2DS group. They had significantly lower methylation levels at the promoter-associated region, but neither the effect of stressors nor the cg00130530 methylation was found to be associated with the development of psychiatric phenotypes. The methylation level of cg00130530 in the 22q11.2DS group was correlated with legal/crime stressors. It was observed that CNV on chromosome 22 plays a significant role in the determination of psychiatric phenotypes despite the effect of psychological stressors. For future research, additional FKBP5 gene methylation regions, genetic variations, and complex stressor interactions (type x count x severity x duration) should be analyzed.