A link between inflammation and mental health was first noted in the 19th century. In the last 10 years, interest in this subject has gathered pace, as epidemiological, genetic, preclinical and clinical data have all accumulated and demonstrate immune dysregulation in at least some patients with psychiatric disorders. A curiosity about this subject was clearly in evidence from the packed room in this early morning session, which saw many delegates sitting on the floor when there were no more chairs available. Professor Giulio Perugi, from the University of Pisa, Italy, appeared rather surprised. He claimed that, as an Italian, it was very hard for him to understand so many people making the effort to get to the conference centre for the 7:45 start! Nevertheless, our diligence was rewarded with his interesting thoughts on the subject of inflammation, autoimmunity and psychosis.
The relationship between psychiatric and autoimmune disorders or immune dysregulation may be related to their pathogenesis, possibly through shared genetic risk or common aetiologic factors such as infection. A genetic vulnerability combined with an external stressor such as infection early in life may combine to sensitise the immune systems, both in the periphery and the CNS. Once the inflammatory systems of the brain are activated, this can lead to neuronal damage, which may further increase stress on the brain and make further pathological changes more likely. Prof Perugi stated that research in this area points to models for the pathophysiology of psychosis based on genetic vulnerability in combination with another intervening stressor that may have at least as much clinical usefulness as the monoamine hypothesis.
On that basis, Prof Perugi cautioned that may be we are looking in the wrong place for the pathogenesis, and therefore approaches to treatment, for at least some patients with schizophrenia. If some instances of psychosis are not caused by a primary brain disorder, but rather brain pathology secondary to systemic inflammatory effects, then diagnosis and treatment may need to change. In the future, diagnosis on the basis of biological markers (if these could be defined) as well as or even instead of symptomatology could indicate that treatment with anti-inflammatory therapies was appropriate in a subset of patients.