Immune cells in the brain linked to risk of schizophrenia

A new study has found that a type of immune cell is more active in the brains of people at risk of schizophrenia.

The findings, published today in the American Journal of Psychiatry, could change scientists’ understanding of the condition. The research, which also revealed that the immune cells are highly active in people already diagnosed with schizophrenia, opens up new avenues for improving diagnosis and treatment.

Schizophrenia is a severe mental illness that affects around one in 100 people in the UK. It is one of the leading causes of disability in adults and sufferers die, on average, 20 years early, compared with those who do not have the disease. Symptoms include hallucinations, thoughts that are not based in reality and paranoia, alongside depression and social withdrawal.

In the study, researchers at the Medical Research Council (MRC) Clinical Sciences Centre at Imperial College London used a type of brain scan called a positron emission tomography (PET) scan. This technology measured immune system activity, which is also known as inflammation.

The team were tracking a type of immune cell called microglia, which responds to damage and infection in the brain. They are also responsible for a process known as pruning – where connections between the brain cells are rearranged to enable the cells to work as well as possible. Earlier studies have suggested that these cells may be involved in schizophrenia. One theory is that the cells make errors in their pruning, and make inappropriate connections between cells.

Other studies have also implicated microglia in other brain conditions, including Alzheimer’s and depression.

The study team, which also included researchers from King’s College London, tested a group of 56 people.  From this group, 14 were classified as at high-risk of schizophrenia (they may have been experiencing depression and anxiety, and occasional hallucinations), and 14 had been diagnosed with schizophrenia. The remainder of patients were healthy controls.

The researchers found that activity levels of microglia in the brain increased according to the severity of symptoms in people with schizophrenia.

Peter Bloomfield, lead author of the study at the MRC Clinical Sciences Centre, and who was supervised by Dr Vincenzo De Paola and Dr Oliver Howes, said: “Our findings are particularly exciting because it was previously unknown whether these cells become active before or after onset of the disease."

“Now we have shown this early involvement, mechanisms of the disease and new medications can hopefully be uncovered.”

Dr Oliver Howes, head of the psychiatric imaging group at the MRC Clinical Sciences Centre, added: “Schizophrenia is a potentially devastating disorder and we desperately need new treatments to help sufferers.”

“This is a promising study as it suggests that inflammation may lead to schizophrenia and other psychotic disorders. We now aim to test whether anti-inflammatory treatments can target these.”

Professor Hugh Perry, Chair of the Neuroscience and Mental Health Board at the MRC, added: “Schizophrenia, like other mental health disorders, is a complex disease that we know is caused by an interplay of genetic, behavioural and other contributing factors.

“This study adds to a growing body of research that inflammation in the brain could be one of the factors contributing to a range of disorders – including Alzheimer’s, schizophrenia and depression - and with this new knowledge comes the hope of life-changing treatments.”

The research was funded by the MRC and King’s College London.

Reference: "Microglial Activity in People at Ultra High Risk of
Psychosis and in Schizophrenia: An [11C]PBR28
PET Brain Imaging Study", American Journal of Psychiatry, published 16th October 2015