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  • Between Bedside and Bench
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Puzzling over schizophrenia: Schizophrenia as a pathway disease

Effective treatment for schizophrenia is still an unmet clinical need. Alleviating problems associated with cognitive impairment and finding the root of the disease remain priorities for clinicians and scientists. The incomplete understanding of the basis of this pathology has urged for research that will unravel the genetic origin of schizophrenia. But studies involving environmental exposure and social impact have also hinted at extrinsic factors as players in the pathogenesis of schizophrenia, which may be exploited to prevent the development of the disease. In 'Bench to Bedside', Patrick Sullivan proposes a model putting forward how genetic variants may confer risk by functioning together within the same pathway. This disease pathway hypothesis would imply a polygenetic variation affecting the same pathway and the alteration of a transcriptional network as a root for increasing schizophrenia risk. In 'Bedside to Bench', Andreas Meyer-Linderberg and Heike Tost discuss human-based population studies that suggest that environmental factors linked to development of schizophrenia can affect brain regions involved in the human social-emotional processing network. Genetic risk variants for schizophrenia can also influence similar regions in the brain, suggesting that environmental and intrinsic factors may converge in the same neural circuit.

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Figure 1: Schematic of schizophrenia as a pathway disease.

References

  1. van Os, J. & Kapur, S. Lancet 374, 635–645 (2009).

    Article  CAS  Google Scholar 

  2. Collins, P.Y. et al. Nature 475, 27–30 (2011).

    Article  CAS  Google Scholar 

  3. World Health Organization. The global burden of disease: 2004 update. http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf (2008).

  4. Friedhoff, A.J. & Van Winkle, E. Nature 194, 897–898 (1962).

    Article  CAS  Google Scholar 

  5. Sherrington, R. et al. Nature 336, 164–167 (1988).

    Article  CAS  Google Scholar 

  6. Ripke, S. et al. Nat. Genet. 43, 969–976 (2011).

    Article  CAS  Google Scholar 

  7. Levinson, D.F. et al. Am. J. Psychiatry 168, 302–316 (2011).

    Article  Google Scholar 

  8. International Schizophrenia Consortium et al. Nature 460, 748–752 (2009).

  9. Barabási, A.L., Gulbahce, N. & Loscalzo, J. Nat. Rev. Genet. 12, 56–68 (2011).

    Article  Google Scholar 

  10. Lichtenstein, P. et al. Lancet 373, 234–239 (2009).

    Article  CAS  Google Scholar 

  11. Stefansson, H. et al. Nature 460, 744–747 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Kwon, E., Wang, W. & Tsai, L.H. Mol. Psychiatry advance online publication, 10.1038/mp.2011.170 (20 December 2011).

  13. Szulwach, K.E. et al. J. Cell Biol. 189, 127–141 (2010).

    Article  CAS  Google Scholar 

  14. Smrt, R.D. et al. Stem Cells 28, 1060–1070 (2010).

    Article  CAS  Google Scholar 

  15. Visscher, P.M. et al. Am. J. Hum. Genet. 90, 7–24 (2012).

    Article  CAS  Google Scholar 

  16. Lee, S. et al. Nat. Genet. (in the press).

  17. Voineagu, I. et al. Nature 474, 380–384 (2011).

    Article  CAS  Google Scholar 

  18. Sullivan, P. Mol. Psychiatry 17, 2–3 (2011).

    Article  Google Scholar 

  19. Yang, J., Wray, N.R. & Visscher, P.M. Genet. Epidemiol. 34, 254–257 (2010).

    Article  Google Scholar 

  20. Lango Allen, H. et al. Nature 467, 832–838 (2010).

    Article  CAS  Google Scholar 

Download references

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Correspondence to Patrick F Sullivan.

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Sullivan, P. Puzzling over schizophrenia: Schizophrenia as a pathway disease. Nat Med 18, 210–211 (2012). https://doi.org/10.1038/nm.2670

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