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Overview of the inflammatory evidence for the psychosis continuum model
Interview with Prof. Ole Andreassen, recorded at ECNP Congress 2016, Vienna
Could you give a background to the psychosis continuum mode?
The psychosis continuum is an old concept, back from Kraepelin over 100 years ago and it is building on the fact that there are overlapping clinical characteristics between schizophrenia and bipolar disorder, so it’s like a continuum of psychosis across these diagnostic categories.
Then it has been sort of hard to study this related to immune factors because most groups they do analysis or investigate schizophrenia or they investigate bipolar so it’s hard to sort of compare directly.
What we did, we recruited a large sample of nearly 500 participants with schizophrenia and the same number of affective psychosis or bipolar disorder and then had the controls and then we could show that there is an overlap in immune markers, cytokines in the plasma between schizophrenia and bipolar disorder and these are related to mainly the TNF, tumour necrosis factor and interleukin. These two markers of inflammatory activity are increased, strongest in schizophrenia but then there is some increase also in bipolar and then very little in controls.
This is sort of showing me that there is also an overlap in immune factors across the psychosis continuum.
Could you describe your work looking at inflammatory markers?
Inflammatory markers, they have been studied in many ways and in many projects. The new thing here is that we investigated the same markers in the same samples when the patients were recruited to the same clinic and they were assessed in the same way. All the blood samples were drawn sort of not with any bias or that they took all the patients with one diagnosis one year and the other diagnosis another year but they were all mixed, so that’s why we were able to compare directly between the different diagnostic categories across the psychosis continuum.
I think this is one thing that has not been done often before and then also we had a really large group so we were able to detect also small differences because it is not like their immune levels are much, much higher in patients compared to control; it is very small differences, but they are significant.
What was you methodology?
This is a study we included nearly 900 patients and 400, 500 controls and all of them were screened and those that had an ongoing infection or were treated with immune-modulating agents were not included, they were removed from the study. Then we measured a series of key inflammatory markers or cytokines, in particular this TNF and also interleukins but then we also did some other ones, von Willebrand factor and OPG, osteoprotegerin.
Then we sort of did everything at once; it was not like any bias in the way we analysed them, so everything was done in the same lab, at the same time and that’s where we discovered this significant but sort of subtle increase in this interleukin-1 and TNF-alpha.
What could be the clinical implications in the future?
Short-term I think it links the immune system to the psychotic disorders so I think clinicians should be aware that there could be some inflammatory activity going on to be sure that there is no infection or no comorbidity with any immune disease, then there is still lacking evidence for interventions. I think this is what really is needed now to start branding intervention studies to see if modulating immune activity could also help the core disease phenotypes like delusions or hallucinations.
There are studies ongoing, several studies attacking the immune system but I think we still need more understanding of the mechanisms, the underlying link between the immune system and clinical disease. I think the association could be that it is only like secondary, that people with schizophrenia or bipolar disorder, they have stressful lives so they have like an increase in immune activity, but that is a secondary phenomenon.
But since there are now recently so many risk genes discovered for these diseases that are associated with the immune system, that sort of suggests a more primary, that there are some susceptibility genes affecting the immune system and that’s why people develop the disease.
What is your take-home message?
The take-home message is that in psychotic disorders there is a clear evidence for an increase in markers related to the inflammatory system and this seems to be associated with development of the disease and I think this is really opening up for new avenues in treatment in the future.