Study of neonatal inflammatory markers and later risk of schizophrenia

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Philip Rising Nielsen, Postdoc, Centre for Register-based Research, Aarhus University

The aim of this study was to measure whether the level of different inflammatory markers in neonatal blood had an association with developing schizophrenia later in life. This is the largest study of cytokine levels in neonates and schizophrenia.

Several different kinds of immune molecules, including cytokines, major histocompatibility complex proteins, and complement are expressed in the developing and adult brain and have critical functions in brain development and plasticity. The role of the immune system in neurodevelopment and potential effects on brain and behavior in adulthood remains relatively unexplored. In keeping with the neurodevelopmental effects of cytokines, we thought it of prime importance to investigate cytokines in neonate life.

We investigated 17 inflammatory markers and found no association between cytokine levels and schizophrenia. This may at first seem surprising since many cytokines and cytokine receptors are constitutively expressed during brain development both in rodents and in humans, suggesting essential roles for these molecules in the regulation and modulation of normal brain development. It was thus expected that abnormal levels of these molecules during neonatal life potentially could adversely affect neurodevelopmental processes and contribute to a higher susceptibility to a complex brain disorder of developmental origin such as schizophrenia.

Although we did not find an association with schizophrenia, the findings of this study are novel and interesting, because the neonatal immune system has received very little attention in the literature. The possibility of being able to examine this association is truly unique. The lack of a difference in cytokine levels between controls and cases in this study warrants further study as the reasons for no association with schizophrenia are not clear at present.

The article "Neonatal Levels of Inflammatory Markers and Later Risk of Schizophrenia" was published in Biological Psychiatry 2014, 22 July (Epub ahead of print).

Facts about the study

  • The nested case-control study is based on data derived from the Danish Psychiatric Central Register, the Danish Civil Registration System, and the Danish Neonatal Screening Biobank
  • 17 inflammatory markers were measured in eluates from dried blood spots using a bead-based multiplex assay
  • The study includes 995 cases with schizophrenia and 980 control subjects
  • The study found no association between neonatal inflammatory marker levels and schizophrenia

Further information:

Philip Rising Nielsen, Postdoc, National Centre for Register-Based Research, Aarhus University, Emil: