Over the last few decades, a steady stream of studies has suggested links between autoimmune disorders and schizophrenia. However, the findings have been patchy, and often based on under-powered studies. In a new study from Eaton and colleagues at the National Centre for Register-based Research (based in Aarhus, Denmark), it has been convincingly shown that a range of autoimmune disorders positively co-segregate with schizophrenia at both the individual and parental level. This study reconfirms the power of register-based epidemiological research to generate clues that can guide future research.
There are some curious twists to these data. Table 3 shows that Type 1 diabetes appearing before the onset of schizophrenia occurred less frequently compared to control subjects; however, this association was only a trend level (Adjusted Incidence Rate 0.07, 95 percent CI 0.4, 1.0). On the other hand, in the parents of individuals with schizophrenia, Type 1 diabetes was twice as common compared to control parents. The authors also note that rheumatoid arthritis occurred more frequently in parents of those with schizophrenia compared to control parents. In light of the negative co-segregation between schizophrenia and rheumatoid arthritis at the individual level, this finding defies simple explanation.
The co-segregation between these disorders does not necessarily mean that autoimmune mechanisms are involved in schizophrenia. Evolution tends to recycle strategies that work, and there is now good evidence demonstrating that proteins first identified in immune function (e.g., MHC proteins) apparently play very different roles in brain development and adult brain functioning (Boulanger and Shatz, 2004). In some ways, this should not come as a surprise. The immune system and the nervous system are both designed to extract and store information from the environment.
The take-home message from this study is that those interested in the etiopathogenesis of schizophrenia should keep a close eye on what is happening in immunology research. The matrix of gene by environmental factors that lead to susceptibility to schizophrenia seems to overlap with pathways to autoimmune disorders. Watch this space.
Boulanger LM, Shatz CJ. Immune signalling in neural development, synaptic plasticity and disease. Nat Rev Neurosci. 2004 Jul 1;5(7):521-31 AbstractView all comments by John McGrath