Could anti-inflammatory drugs prevent schizophrenia?

Behind the Headlines

Monday October 19 2015

Schizophrenia affects around 1 in 100 people

Immune overactivity may be a sign of schizophrenia

"It may be possible to prevent schizophrenia by calming the brain's immune system," BBC News reports after researchers found raised levels of immune activity in people thought to be at high risk of developing schizophrenia.

The research looked at the activity of a type of cell known as microglial cells. These serve as the primary immune cells for the brain and central nervous system, protecting these vital regions of the body against infection.

Researchers recruited people who already had schizophrenia, as well as those at high risk of developing the condition. Brain scans showed microglial cell activity was higher in high-risk individuals and those with schizophrenia when compared with a healthy group.

The researchers also observed a positive relationship between microglial activity and the severity of psychosis symptoms in high-risk individuals. They speculated this immune overactivity could "scramble" the normal working of the brain, triggering the symptoms of schizophrenia.

But the results should be interpreted with some caution because of some of the study's limitations. The study included just 56 individuals split into four groups of 14: those with schizophrenia, those at risk, and two control groups. And we don't know whether microglial activity is a cause or a consequence of schizophrenia.

In a related press release, the researchers warn against people self-medicating with anti-inflammatory drugs without medical supervision. They hope to carry out a clinical trial in the future looking at whether anti-inflammatory drugs could play a useful role in controlling schizophrenia. 

Schizophrenia

Schizophrenia is a long-term mental health condition that causes a range of different psychological symptoms, including:

  • hallucinations – hearing or seeing things that do not exist
  • delusions – unusual beliefs not based on reality that often contradict the evidence
  • muddled thoughts based on hallucinations or delusions
  • changes in behaviour

Read more about the symptoms of schizophrenia.

Where did the story come from?

The study was carried out by researchers from Imperial College London and King's College London in the UK, the University of Padova, Italy, and the University of Texas Health Science Center.

It was funded by multiple UK organisations, such as the Medical Research Council, the Maudsley Charity, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London, Maudsley NHS Foundation Trust, and King's College London.

The study was published in the peer-reviewed American Journal of Psychiatry.

It was widely reported on by the UK media, both accurately and responsibly. The Guardian's reporting was particularly useful and insightful as it was written by neuroscientist Mo Costandi.

However, some of the limitations of the study were not explicitly pointed out in some sections of the media. BBC News quoted one of the authors, Dr Oliver Howes, as saying: "This is a real step forward in understanding [schizophrenia].

"For the first time we have evidence that there is overactivity even before full onset of the illness. If we could reduce activity [before full-blown illness] then we might be able to prevent the illness – that needs to be tested, but is one key implication [of the research]." 

What kind of research was this?

This was an observational study where the researchers used special brain scanning techniques – positron emission tomography (PET) scan – to compare the activity of microglial cells in people with schizophrenia or at high risk of the condition, compared with a healthy control group.

Microglial cells are immune cells present in the brain and spinal cord. They act as the first and main form of immune defence for the central nervous system (CNS).

Researchers say there is evidence indicating elevated microglial activity in high-risk individuals and individuals with schizophrenia.

This elevated activity is also associated with a reduction in grey matter volume in high-risk individuals and those with schizophrenia. Grey matter contains the nerve cell bodies and is where all the main functions, thoughts and emotions of the body are processed.

In this study, researchers investigated whether microglial activity was elevated in the grey matter of high-risk individuals and those with the condition, compared with healthy controls.  

What did the research involve?

This study included 56 individuals:

  • 14 individuals at high risk of schizophrenia (average age 24 years) were compared with 14 age-matched comparison subjects (28 years)
  • 14 individuals with schizophrenia (47 years) were compared with 14 healthy subjects (46 years)

Adults (age 18 or over) were recruited to the study if they had no significant physical or mental health conditions on assessment. 

This included no past history of head injury, use of antipsychotics, benzodiazepines (a type of tranquiliser), substance abuse or dependence, and no recent use of anti-inflammatories. Potential control subjects were also excluded if they had a personal history of mental health illness or a family history of schizophrenia.

Those with, or at risk of, schizophrenia were assessed using standard diagnostic scales. Those considered at high risk are people starting to display symptoms of psychosis that is beginning to have an influence on their normal daily functioning. It is estimated about a third of these people will develop schizophrenia within two years.

PET scans were performed for all the study subjects to see how cells in the brain where working. They also had an MRI scan to look at the general structure of the brain. 

What were the basic results?

Overall, microglial activity was significantly higher in high-risk individuals when compared with healthy control subjects.

Similar results were observed in individuals with schizophrenia compared with their healthy comparison group.

A positive correlation between the severity of symptoms and microglial activity in high-risk individuals was also observed.  

How did the researchers interpret the results?

The researchers concluded by saying this study is the first, to their knowledge, to find evidence of elevated brain microglial activity in people at high risk of psychosis.

The results also show greater microglial activity is associated with more severe symptoms. 

Conclusion

This observational study aimed to assess whether there was a difference in the activity of the main immune cells of the brain and spinal cord (microglial cells) between those at high risk of developing schizophrenia, people who already have schizophrenia, and healthy population controls.

The study found microglial activity was higher in individuals with schizophrenia and at high risk of the condition compared with the healthy controls. The researchers also observed a positive relationship between microglial activity and severity of symptoms in high-risk individuals.

However, the results should be interpreted with some caution because of this study's limitations. The study included just 56 individuals split into groups of 14 with schizophrenia, people at risk, and control groups. Results in these small numbers cannot be generalised to the overall population with or without schizophrenia. Different results may have been obtained in other samples.

Also, although researchers have adjusted for some specific genetic factors, there may be various unmeasured physical and mental health and lifestyle factors influencing the results. And importantly, though the study observed higher microglial activity in people with or at very high risk of schizophrenia, we do not know whether this observation is a cause or a consequence of the condition.

These results are from one-off scans of brain activity. We do not know whether increased microglial cell activity may predispose people to develop psychosis, or whether increased activity may be a change that occurs in people with psychosis – the classic chicken and egg dilemma.

Cohort studies that follow the brain images of people before schizophrenia develops and through the course of their condition would be beneficial to better look at this. It would also be useful to know whether microglial activity changes with antipsychotic medication.

Overall, the results of this study may help to further our understanding of schizophrenia and the factors that may be involved in the disease process. But this study's limitations make it difficult to know whether these findings could have any potential preventative or treatment implications in the future.

The research team are planning to carry out a clinical trial looking at whether anti-inflammatory drugs could help relieve, or even prevent, the symptoms of schizophrenia.     

If you, or anyone you know, is experiencing changes or disturbances in their thought patterns, behaviour or daily functioning that seem different for them, it is important to contact their GP.

With treatment, many people can recover from schizophrenia or at the very least reduce the severity of their symptoms. Read more about how schizophrenia is treated.

Analysis by Bazian. Edited by NHS Choices. Follow NHS Choices on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Immune clue to preventing schizophrenia. BBC News, October 16 2015

Brain's immune cells hyperactive in schizophrenia. The Guardian, October 16 2015

New test 'could screen for schizophrenia before it develops'. ITV News, October 16 2015

Schizophrenia 'could be prevented by calming overactive immune system'. The Daily Telegraph, October 16 2015

Links to the science

Bloomfield PS, Selvaraj S, Veronese M, et al. Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [11C]PBR28 PET Brain Imaging Study. The American Journal of Psychiatry. Published online October 16 2015

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Media last reviewed: 22/04/2015

Next review due: 22/04/2017

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