September 17, 2018

expert reaction to schizophrenia and immune cells in the brain

Research published in Molecular Psychiatry that identifies immune cells in greater amounts in the brains of some people with schitozophrenia.

Dr Mark Dallas, Associate Professor in Cellular Neuroscience, University of Reading, said:

“The is a growing awareness of the role the immune system plays in brain disease.  This study highlights some biological markers that could provide future drug targets.  Interestingly it highlights some key changes that link changes in the blood to those in the brain.  It remains to be seen if these changes are a result of schizophrenia or indeed cause schizophrenia.”

Prof David Male, Immunology and Cell Biology Research Group, The Open University, said:

“The paper continues a line of research that has identified a low grade inflammation in individuals with schizophrenia – this in itself has been controversial and the biological relevance even more disputed.  They have done well to get a large set of tissues and carried out the analyses carefully.  While they have made great efforts to carefully match the patients and control subjects, there is always the limitation that the patients are being treated with drugs and the controls are not.  Hence differences between patients and controls may relate to the treatment rather the underlying cause of the condition.

“The major difficulty in interpreting these studies is that the variation between individuals in the inflammatory markers tested greatly exceeds the differences between schizophrenia patients and control subjects.  In the paper they conclude that it is not possible to disentangle cause and effect.  However one interesting finding is that a transporter that normally protects the brain from toxic molecules and excludes many therapeutic drugs from the brain is lower in one group of patients with schizophrenia.  Although not the main focus of the paper this itself could be the most important observation.”

Prof David Attwell FMedSci, Jodrell Professor of Physiology, UCL, said:

“This paper reports an interesting correlation between the occurrence of schizophrenia and the amount present in the (post mortem) brain of a molecule involved in inflammation (i.e. part of the mechanism that the body’s immune system uses to respond to injury or dysfunction).  A role for inflammation and immune cells in psychiatric illness has been suggested previously (contrary to what is stated in the press release).

“Specifically, the paper reports that levels of the cell adhesion molecule ICAM1, which helps immune cells (leukocytes) to enter the brain, are increased in schizophrenia patients.  Indeed some evidence presented in the paper suggests that more leukocytes are present in the brains of schizophrenics, although this was not quantified in detail.  However, despite the mean levels of ICAM1 present being significantly different, there is a large overlap in the ranges of the amount of ICAM1 present in normal and schizophrenic brains.  Most importantly, the paper does not establish whether the difference in ICAM1 level is a cause of schizophrenia or an effect of it.  Indeed, there is some evidence in the paper that being on long-term anti-psychotic medication may contribute to the elevation of ICAM1 level.

“These facts make it hard to view this report as providing a ‘magic bullet’ approach to treating schizophrenia, but the work is worth following up on to establish its reproducibility, and to try to separate whether the elevated ICAM1 level is a cause or an effect of schizophrenia.”

Dr Niels Haan, Research Associate, Neuroscience and Mental Health Research Institute, Cardiff University, said:

“Contrary to what the press statement states, immune cells both in the brain and in the rest of the body have been a hot topic in schizophrenia research for at least the last decade, and they have not been seen as passive surveillance cells by anyone for many years. This paper does suggest an interesting potential role of the cells lining the blood vessels of the brain, and shows how changes in these cells may be involved in getting immune cells into the brain in some schizophrenia patients. However, they do not show these immune cells actually enter the brain, or that they contribute to the disease there. At most this paper points to an interesting new area of research, but a lot more work needs to be done before we can tell whether this could be of any use for treatment.”

Prof John Hardy FMedSci, Professor of Neuroscience, UCL, said:

“This is an interesting piece of work which certainly adds to the evidence that the inflammation processes are important in schizophrenia.  The work is well done and invites both replication and follow up.  In fact we are beginning to realise the roles of non-neuronal cells in neurological diseases in general is more important than we had appreciated.”

* ‘Increased macrophages and changed brain endothelial cell gene expression in the frontal cortex of people with schizophrenia displaying inflammation’ by Cai et al. will be published in Molecular Psychiatry at 11:00 UK time on Friday 14^th September, which is also when the embargo will lift.

Declared interests

Dr Mark Dallas: “Nothing to disclose.”

Prof David Male: “I do not have any vested interests in this research. And I do not directly know the authors.”

Prof David Attwell: “I have no conflicting interest.”

Dr Niels Haan: “No interests to declare”

Prof John Hardy: None received.