Brain Inflammation Linked to Schizophrenia Risk

Megan Brooks

October 21, 2015

Immune cells in the brain (microglia) are more active in individuals with schizophrenia and those at very high risk for the disorder, according to new study.

The finding suggests that neuroinflammation plays a role in schizophrenia and points to a "new potential target" for treatment and prevention, Oliver D. Howes, MD, PhD, head of the psychiatric imaging group at the Medical Research Council (MRC) Clinical Sciences Centre at Imperial College London, told Medscape Medical News.

The study was published online October 16 in the American Journal of Psychiatry.

Novel Findings

The research team used positron emission tomography scans to measure microglial activity in 56 adults, including 14 who had been diagnosed with schizophrenia, 14 at "ultra–high risk" for psychosis, and 28 healthy matched control individuals who had no symptoms or heightened risk for the disorder.

PET imaging signal in healthy volunteers, high-risk persons, and patients with schizophrenia showing a stepwise elevation in microglial activity (orange) as severity of illness increases.

They found that microglial activity in gray matter was elevated in ultra-high-risk individuals compared with the matched control participants (Cohen's d >1.2) and was positively correlated with symptom severity (r = 0.730). Microglial activity was also elevated in patients with schizophrenia relative to matched control participants (Cohen's d >1.7).

Microglia, the brain's immune cells (green), with cell nuclei (red).

"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," lead author Peter Bloomfield, from the MRC Clinical Sciences Centre, said in a news release.

"Schizophrenia, like other mental health disorders, is a complex disease that we know is caused by an interplay of genetic, behavioral, and other contributing factors," Prof Hugh Perry, chair of the Neuroscience and Mental Health Board at the MRC, who was not involved in the study, noted in the release.

"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," he said.

"We are seeking funding to do a study using a treatment that we hope will reduce the overactivity in microglia that we saw in this study. If this approach works, then it could lead to full- scale clinical studies," Dr Howes told Medscape Medical News.

Immune Dysfunction

Reached for comment, Brian Miller, MD, assistant professor, Department of Psychiatry and Health Behavior, Georgia Regents University, in Augusta, described the study as "important" and the first to find evidence for microglial activation in people at ultra–high risk for psychosis, which complements and extends previous work that has demonstrated microglial activation in patients with schizophrenia.

The findings, Dr Miller told Medscape Medical News, "provide additional support for the hypothesis that immune dysfunction may be involved in the etiopathophysiology of psychosis in some people, and warrants replication in larger samples."

"The authors raise the possibility that anti-inflammatory treatment may be effective in preventing the onset of psychosis. While this hypothesis certainly merits further investigation, it is important to note that there is mixed evidence in schizophrenia suggesting that adjunctive treatment with anti-inflammatory agents may be associated with modest improvements in psychopathology in some patients," Dr Miller noted.

The research was funded by the MRC and King’s College London. Dr Howes has participated in advisory/speaker meetings with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck, Lyden-Delta, Otsuka, Servier, and Roche. The original article contains a complete list of author disclosures.

Am J Psychiatry. Published online October 16, 2015. Abstract

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