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

Mihaljevic, Marina, Zeljic, Katarina, Soldatovic, Ivan, Andric, Sanja, Mirjanic, Tijana, Richards, Alexander, Mantripragada, Kiran, Pekmezovic, Tatjana, Novakovic, Ivana and Maric, Nadja P. 2017. The emerging role of the FKBP5 gene polymorphisms in vulnerability-stress model of schizophrenia: further evidence from a Serbian population. European Archives of Psychiatry and Clinical Neuroscience 267 (6) , pp. 527-539. 10.1007/s00406-016-0720-7

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Abstract

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

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Springer
ISSN: 0940-1334
Date of First Compliant Deposit: 10 November 2016
Date of Acceptance: 22 August 2016
Last Modified: 20 Dec 2017 05:40
URI: http://orca.cf.ac.uk/id/eprint/96018

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