Investigation of Fasciculation and Elongation Protein ζ-1 (FEZ1) in Peripheral Blood Reveals Differences in Gene Expression in Patients with Schizophrenia

Open access


Schizophrenia (SZ) is a chronic neuropsychiatric disorder characterized by affective, neuromorphological and cognitive impairment, deteriorated social functioning and psychosis with underlying molecular abnormalities, including gene expression changes. Observations have suggested that fasciculation and elongation protein ζ-1 (FEZ1) may be implicated in the pathogenesis of schizophrenia. Nevertheless, our current knowledge of the expression of FEZ1 in peripheral blood of schizophrenia patients remains unclear. The purpose of this study was to identify the characteristic gene expression patterns of FEZ1 in peripheral blood samples from schizophrenia patients. We performed quantitative reverse-transcriptase (qRT-PCR) analysis using peripheral blood from drug-free schizophrenia patients (n = 29) and age and gender-matched general population controls (n = 24). For the identification of FEZ1 gene expression patterns, we applied a comparative threshold cycle (CT) method. A statistically significant difference of FEZ1 mRNA level was revealed in schizophrenia subjects compared to healthy controls (p = 0.0034). To the best of our knowledge, this study is the first describing a down-regulation of FEZ1 gene expression in peripheral blood of patients with schizophrenia. Our results suggested a possible functional role of FEZ1 in the pathogenesis of schizophrenia and confirmed the utility of peripheral blood samples for molecular profiling of psychiatric disorders including schizophrenia. The current study describes FEZ1 gene expression changes in peripheral blood of patients with schizophrenia with significantly down-regulation of FEZ1 mRNA. Thus, our results provide support for a model of SZ pathogenesis that includes the effects of FEZ1 expression.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Perala J Suvisaari J Saarni SI Kuoppasalmi K Isometsä E Pirkola S et al. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry. 2007; 64(1): 19-28.

  • 2. Ng MY Levinson DF Faraone SV Suarez BK DeLisi Le Arinami T et al. Meta analysis of 32 genome-wide linkage studies of schizophrenia. Mol Psychiatry. 2009; 14(8): 774-785.

  • 3. Shi J Levinson DF Duan J Sanders AR Zheng Y Pe’er I et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature. 2009; 460(7256): 753-757.

  • 4. Stefansson H Ophoff RA Steinberg S Andreassen OA Cichon S Rujescu D et al. Common variants conferring risk of schizophrenia. Nature. 2009; 460(7256): 744-747.

  • 5. Purcell SM Wray NR Stone JL Visscher PM O’Donovan MC Sullivan PF et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009; 460(7256): 748-752.

  • 6. Vawter MP Ferran E Galke B Cooper K Bunney WE Byerley W et al. Microarray screening of lymphocyte gene expression differences in a multiplex schizophrenia pedigree. Schizophr Res. 2004; 67(1): 41-52.

  • 7. Kuzman MR Medved V Terzic J Krainc D. Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia. J Psychiatr Res. 2009; 43(13): 1073-1037.

  • 8. Miyoshi K Honda A Baba K Taniguchi M Oono K Fujita T et al. Disrupted-In-Schizophrenia 1 a candidate gene for schizophrenia participates in neurite outgrowth. Mol Psychiatry. 2003; 8(7): 685-694.

  • 9. Lipska BK Peters T Hyde TM Halim N Horowitz C Mitkus T et al. Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs. Hum Mol Genet. 2006; 15(8): 1245-1258.

  • 10. Sakae N Yamasaki N Kitaichi K Fukuda T Yamada M Yoshikawa H et al. Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants. Hum Mol Genet. 2008; 17(20): 3191-3203.

  • 11. Moens LN de Rijk P Reumers J van den Bossche MJ Glassee W de Zutter S et al. Sequencing of DISC1 pathway genes reveals increased burden of rare missense variants in schizophrenia patients from a Northern Swedish population. PLoS ONE. 2011; 6(8): e23450. doi: 10.1371/ journal.pone.0023450.

  • 12. Chubb JE Bradshaw NJ Soares DC Poeteous DJ Millar JK. The DISC locus in psychiatric illness. Mol Psychiatry. 2008; 13(1): 36-64.

  • 13. Abdolmaleky HM Cheng KH Faraone SV Wilcox M Glatt SJ Gao F. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet. 2006; 15(21): 3132-3145.

  • 14. Wang J Robinson JF Khan HM Carter DE McKinney J Miskie BA et al. Optimizing RNA extraction yield from whole blood for microarray gene expression analysis. Clin Biochem. 2004; 37(9): 741-744.

  • 15. Yu Z Ono C Kim HB Komatsu H Tanabe Y Sakae N et al. Four mood stabilizers commonly induce FEZ1 expression in human astrocytes. Bipolar Disord. 2011; 13(5-6): 486-499.

  • 16. Livak KJ Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-ΔΔ C(T)) method. Methods. 2001; 25(4): 402-408.

  • 17. Austin CP Ky B Ma L Morris JA Shughrue PJ. Expression of disrupted-in-Schizophrenia-1 a schizophre-nia-associated gene is prominent in the mouse hippocampus throughout brain development. Neuroscience. 2004; 124(1): 3-10.

  • 18. Honda A Miyoshi K Baba K Taniguchi M Koyama Y Kuroda S et al. Expression of fasciculation and elongation protein zeta-1 (FEZ1) in the developing rat brain. Brain Res Mol Brain Res. 2004; 122(1): 89-92.

  • 19. Koga M Ishiguro H Horiuchi Y Albalushi T Inada T Iwata N et al. Failure to confirm the association between the FEZ1 gene and schizophrenia in a Japanese population. Neurosci. Lett. 2007; 417(3): 326-329.

  • 20. Nohesara S Ghadirivasfi M Mostafavi S Eskandari MR Ahmadkhaniha H Thiagalingam S et al. DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder. J Psychiatr Res. 2011; 45(11): 1432-1438.

Journal information
Impact Factor

IMPACT FACTOR 2018: 0.769
5-year IMPACT FACTOR: 0.892

CiteScore 2018: 0.66

SCImago Journal Rank (SJR) 2018: 0.274
Source Normalized Impact per Paper (SNIP) 2018: 0.372

Cited By
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 174 100 4
PDF Downloads 82 61 1