Schizophrenia is among the most expensive disorders in terms of quality of life and societal cost. While treatments are inadequate, early intervention has been shown to be clinically effective. Consequently, there is an urgent need to improve our understanding of the pathophysiology of this disorder so that we can identify and treat earlier. Growing evidence for an inflammatory component to the disorder has clear implications for early identification, treatment and potentially prevention. The evidence is several-fold;
1. Prenatal maternal infection, and elevated markers of inflammatory processes during the postnatal period and early childhood, increase the risk of subsequent schizophrenia.
2. Subjects with schizophrenia show evidence of increased blood markers of inflammation.
3. Recent postmortem brain research suggests that there may be an inflammatory subtype of the disease.
4. Preliminary evidence suggests that anti-inflammatory agents may have therapeutic effects in schizophrenia.
In addition there is genetic and neuroimaging support for an inflammatory contribution to the disorder. There are, however, important gaps in our knowledge:
1. Firstly, it is not clear whether raised inflammatory markers distinguish those who transition to psychosis compared to those who do not among a population at risk of psychosis.
2. Secondly, we do not know how inflammatory markers change over time in individuals at risk of psychosis. This longitudinal information is critical as it will inform us whether the proposed vulnerability represented by raised inflammatory markers is a state- or trait-vulnerability, and the degree to which it is modifiable.
We propose to study the pattern of change in inflammatory markers from childhood and adolescence (age 12) and late adolescence (age 18), and early adulthood (age 25) among a cohort of subjects at risk for psychosis. This proposal is based on longitudinal clinical characterisation and biosampling of subjects in the Avon Longitudinal Study of Parents and Children.
