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Association between single nucleotide polymorphism of the FKBP5 gene and neural correlates of attentional bias towards emotional stimuli in depression

Leonardo Tozzi1*, Thomas Frodl1, 2, 3, Angela Carballedo1, 2, Friedrich Wetterling1, Hazel McCarthy1, Michael Gill2, Derek Morris2, Veronica O'Keane4, Ciara Fahey5 and James Meaney5
  • 1 Trinity College Institute of Neuroscience, Ireland
  • 2 St James’s Hospital, Ireland
  • 3 University of Regensburg, Germany
  • 4 Adelaide and Meath Hospital Dublin, Psychiatry, Ireland
  • 5 Neuropsychiatric Genetics Group, Department of Psychiatry and Institute of Neuroscience, Ireland

Recent research suggests a role of FKBP5, a glucocorticoid receptor (GR) regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders (Fani et al., 2014; Lavebratt et al. 2010; Gillespie et al. 2009; Kang et al., 2012; Gen Shinozaki, 2011). In particular, the allele T of FKBP5:rs1360780 appears to be linked to stress hormone dysregulation (Menke et al., 2013). This variant was indeed found to be overrepresented in depressed patients (Lavebratt et al. 2010; Gillespie et al. 2009; Kang et al., 2012; Gen Shinozaki, 2011) and has also been investigated as a candidate for treatment prediction response in this population (Horstmann et al., 2010). Our study aimed to assess the impact of the FKBP5:rs1360780 C/T polymorphism on brain function during an emotional attention bias task using functional magnetic resonance imaging (fMRI) in 33 patients suffering from major depressive disorder and 43 healthy controls. During evaluation of negative emotional responses, we found significantly higher activity in depressed patients compared to healthy controls in posterior Default Mode Network regions (p<0.05, FDR cluster corrected). Patients have shown increased activity in the hippocampus and temporal lobe when evaluating the shape of negative stimuli as opposed to evaluating their emotional valence (p<0.05, FDR cluster corrected). Moreover, we report a significant interaction between diagnosis and the FKBP5 polymorphism, with depressed homozygous C patients compared to T-allele carriers showing significantly greater BOLD responses during non-emotional processing of negative pictures in the insular cortex (p<0.05, FDR cluster corrected, Figure 1). Our results indicate that the T allele of the FKBP5:rs1360780 polymorphism might be associated with a less successful cognitive inhibition of negative emotional content in a subset of patients, maybe due to the effect of the FKBP5 gene on GR function, which in turn might affect the insula and striatum.

Figure 1
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Acknowledgements

European Union’s Seventh Framework Programme for Research

References

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Keywords: FKBP5, Depression, fMRI, emotion, Glucocorticoid receptor

Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014.

Presentation Type: Poster Presentation

Topic: Early Career Neuroscience

Citation: Tozzi L, Frodl T, Carballedo A, Wetterling F, McCarthy H, Gill M, Morris D, O'Keane V, Fahey C and Meaney J (2014). Association between single nucleotide polymorphism of the FKBP5 gene and neural correlates of attentional bias towards emotional stimuli in depression. Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00014

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Received: 10 Sep 2014; Published Online: 10 Sep 2014.

* Correspondence: Dr. Leonardo Tozzi, Trinity College Institute of Neuroscience, Dublin, Ireland, leo.tozzi88@gmail.com