Tijana Mirjanic

The emerging role of the FKBP5 gene polymorphisms in vulnerability-stress model of schizophrenia: further evidence from a Serbian population

Increased reactivity to stress is observed in patients with schizophrenia spectrum disorders and their healthy siblings in comparison with the general population. Additionally, higher levels of neuroticism, as a proposed psychological measure of stress sensitivity, increase the risk of schizophrenia. HPA axis dysregulation is one of the possible mechanisms related to the vulnerability–stress model of schizophrenia, and recent studies revealed a possible role of the functional genetic variants of FK506-binding protein 51 (FKBP5) gene which modulate activity of HPA axis. The purpose of the present study was to investigate impact of FKBP5 on schizophrenia in Serbian patients and to explore relationship between genetic variants and neuroticism by using the case–sibling–control design. In 158 subjects, we measured psychotic experiences, childhood trauma and neuroticism. Nine single-nucleotide polymorphisms (rs9295158, rs3800373, rs9740080, rs737054, rs6926133, rs9380529, rs9394314, rs2766533 and rs12200498) were genotyped. The genetic influence was modeled using logistic regression, and the relationship between genetic variants and neuroticism was assessed by linear mixed model. Our results revealed genetic main effect of FKBP5 risk alleles (A allele of rs9296158 and T allele of rs3800373) and AGTC “risk” haplotype combination (rs9296158, rs3800373, rs9470080 and rs737054, respectively) on schizophrenia, particularly when childhood trauma was set as a confounding factor. We confirmed strong relationship between neuroticism and psychotic experiences in patients and siblings and further showed relationship between higher levels of neuroticism and FKBP5 risk variants suggesting potential link between biological and psychosocial risk factors. Our data support previous findings that trauma exposure shapes FKBP5 impact on schizophrenia.

Neuroticism and facial emotion recognition in healthy adults.

The aim of the present study was to examine whether healthy individuals with higher levels of neuroticism, a robust independent predictor of psychopathology, exhibit altered facial emotion recognition performance.

Openness to experience shortens duration of untreated psychosis in Serbian clinical population.

To determine duration of untreated psychosis (DUP) in patients with schizophrenia‐spectrum disorders from Serbia and to analyse factors that potentially contribute to the treatment delay, with focus on personality traits.

FKBP5 Epigenetic Changes In Schizophrenia: Similarity To Stress-Related Conditions

Background Hypothalamic–pituitary–adrenal (HPA) axis dysregulation is a potential neurobiological mechanism proposed by vulnerability-stress model for schizophrenia. Recent studies highlighted the role of functional genetic variants of FKBP5 gene, which affect the activity of HPA axis following stress exposure, and supported the hypothesis of increased stress sensitivity in schizophrenia. Additionally, FKBP5 demethylation in Intron 7 was observed in stress-related conditions thus the purpose of this pilot study was to investigate FKBP5 methylation levels at Intron 7 in schizophrenia. Methods Ethnically homogeneous Serbian sample of 24 schizophrenia spectrum patients and 24 controls matched by age and gender with patients’ group, were analyzed regarding DNA methylation levels at three CpG sites and average methylation level in Intron 7. Accordingly, we covered the area of GRE that has been reported to be associated with altered stress responsiveness. Epigenetic changes in FKBP5 Intron 7 were measured by Sanger sequencing and compared between the groups using t test as appropriate. Results Analyses revealed decreased FKBP5 methylation at the three targeted CpG sites (CpG1, CpG2, and CpG3) in patients compared to controls (p=0.026, p=0.017, and p=0.027, respectively). Similarly, when we averaged methylation scores of the observed region in Intron 7, significant demethylation was detected in patients (p=0.003). Discussion To the best of our knowledge this is the first study which explored FKBP5 epigenetic changes in schizophrenia. Conclusively to previous stress-related conditions, our preliminary results revealed significant decrease of FKBP5 methylation levels in Intron 7 in patients with schizophrenia. FKBP5 demethylation presents further insight into the reported FKBP5 genetic influence in psychosis and could be promising terapeutic target for the prevention of the onset and the course of schizophrenia.