Friday, October 16, 2015

PET Reveals Inflammatory Response in Schizophrenia, High-Risk Patients

Microglial activity—indicative of an immune response to neuroinflammation—appears to be elevated in the brains of people with schizophrenia and those at high risk of developing schizophrenia, according to a study published today in AJP in Advance. Moreover, the elevated microglial activity appears to be related to symptom severity.

Researchers at the Medical Research Council’s Clinical Sciences Centre, based at Imperial College London, in collaboration with colleagues at King’s College London used positron emission tomography (PET) to measure in vivo microglial activity in patients with schizophrenia, high-risk individuals with pre-clinical symptoms, and healthy controls. (Microglial cells are the immune cells of the brain and are similar to immune-responsive macrophages in the blood; their presence in large numbers indicates inflammation.) The PET method employed a radioactive tracer specific for a protein (known as 18kD translocator-protein, or TSPO) that is indicative of microglial activity.

A total of 56 participants completed the study, including 14 people who met ultra-high risk criteria, as assessed on the comprehensive assessment of the at-risk mental state (CAARMS) and 14 age-matched controls; an additional 14 people with schizophrenia and 14 age-matched healthy controls also participated in the trial.

The authors found that the protein-binding ratio in gray matter was elevated in ultra-high risk subjects compared with matched controls and was positively correlated with symptom severity. Patients with schizophrenia also demonstrated elevated microglial activity with respect to matched controls. Importantly, the researchers found no relationship between depressive symptom severity and the protein binding ratio in gray matter in patients with schizophrenia or ultra-high-risk participants, suggesting the elevated microglial activity is specific to the development of psychotic-like symptoms, rather than psychiatric symptoms in general.

“This is a promising study, as it suggests that inflammation may lead to schizophrenia and other psychotic disorders,” study author Oliver Howes, M.D., Ph.D., said in a press release. “We now aim to test whether anti-inflammatory treatments can target these. This could lead to new treatments or even prevention of the disorders altogether.”

AJP Editor Robert Freedman, M.D. (pictured above), told Psychiatric News that both the findings from the study and the application of the PET method to image pathophysiological processes in the brain may prove transformative. “The PET method now gives clinical researchers an invaluable tool, not before available, to monitor this transition and to search for what might be causing the inflammation,” he continued. “If anti-inflammatory interventions are attempted, then this method can assess whether the intervention has its intended effect.”

For related information, see the Psychiatric News article “Blood Test May Predict Patients Likely to Develop Schizophrenia.”


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