October 16, 2015

expert reaction to new study investigating brain immune cells and inflammation in people with or at risk of schizophrenia

Scientists studying schizophrenia have published their work in the American Journal of Psychiatry which looks at the activity of immune cells in the brain (microglia). They report that activity of these cells was higher in patients with or at risk of schizophrenia, and suggest that inflammation may be a factor in such disorders.

Prof. Stephen Lawrie, Head of Psychiatry, University of Edinburgh, said:

“This is an important paper, which both confirms and extends previous findings, in a carefully controlled and state-of the-art study. The tracer imaging techniques used are an advance on previous studies which have suggested increased microglial activity in schizophrenia but, importantly, also replicate the findings of those early studies.

“The novel finding in this study is that people at high risk, presenting to clinics with psychotic symptoms which do not meet diagnostic criteria for schizophrenia, also showed similarly elevated, but slightly less so, levels of increased microglial activity. This and the correlation shown between the amount of tracer binding and the severity of psychotic symptoms suggest that inflammatory disturbance is involved in the early stages of schizophrenia and may progress as the illness develops. Further, as these high risk participants were not on antipsychotic medication, the differences cannot be due to treatment.  Intriguingly, therefore, this study raises the possibility of earlier detection of a possible ‘neuroinflammatory’ component or sub-type of schizophrenia that might respond to novel therapeutic approaches, such as anti-inflammatory drugs. This, in turn, suggests the possible amelioration or even prevention of one of the worst illnesses affecting mankind.”

Prof. Celso Arango, President-Elect of the European College of Neuropsychopharmacology (ECNP), and Associate Professor of Psychiatry, University of Maryland, said:

“This is a good paper. It is very relevant for two good reasons. Firstly, it measures inflammation (indirectly via glial activation) in the brain, while most previous studies measure it in the blood (peripherically). And secondly, it includes not only a group of patients with schizophrenia but also a group of high risk subjects, and results point towards the first psychotic episode as a therapeutic window for therapies with anti-inflammatory action.

“In the past decade, there has been renewed interest in immune changes, inflammatory processes and oxidative stress changes and their associated consequences as key pathophysiological mechanisms in schizophrenia and related disorders (in fact in almost all psychiatric disorders). Both brain cell components (microglia, astrocytes, and neurons) and immune cells elsewhere in the body have been implicated in inflammation and the resulting oxidative stress in schizophrenia. Furthermore, biological samples from patients have identified that the balance between anti-inflammatory and pro-inflammatory molecules is not present with more weight on the inflammatory side, although the degree and progression of the inflammatory process and the nature of its self-regulatory mechanisms vary from early onset to full-blown disease. A recent paper in Biological Psychiatry with the North American Prodrome Longitudinal Study (NAPLS 2) sample nicely shows that those with fewer anti-inflammatory markers and more grey matter reduction are at higher risk of developing psychosis, and this is in agreement with the present study.

“There are different drugs currently available to address some of these processes of inflammation and their effects on schizophrenia – mainly treatments with anti-inflammatory or antioxidant drugs as add-ons to antipsychotics. In fact a recent meta-analysis (Iris Sommer et al) shows that anti-inflammatory drugs have an effect size for the treatment of psychosis of around 0.4 (effect size is a measure of how efficacious a drug is, it usually goes from 0.2 to 1.2, with a higher number meaning more different from placebo). Different groups including ours are conducting clinical trials with anti-inflammatory antioxidant drugs trying to prevent psychosis, which can be a symptom of schizophrenia, or improve the outcome.”

‘Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [¹¹C]PBR28 PET brain imaging study’ by Peter S. Bloomfield et al. published in the American Journal of Psychiatry on Friday 16 October 2015. 

Declared interests

None received.