Many of the structural and neurochemical features of schizophrenia are present long before the full syndrome of schizophrenia develops. What processes tip the balance between the ultra-high risk states and the development of schizophrenia? One candidate mechanism is cerebral inflammation, studied by Dr. Bart van Berckel and colleagues in the November 1st issue of Biological Psychiatry.

Using positron emission tomography, or PET, imaging, the researchers provide evidence of a brain inflammatory state that may be associated with the development of schizophrenia. The authors reported increased binding levels of [11C]PK11195, a radiotracer with high affinity for the peripheral benzodiazepine receptor (PBR) in patients who had carried the diagnosis of schizophrenia for five years or less. PBR is a molecular target that is present at higher levels in activated microglia. Microglia are activated during inflammatory states. Drs. van Berckel and Kahn further explain: “It was found that microglia activation is present in schizophrenia patients early after disease onset, suggesting brain cells are damaged in schizophrenia. In addition, since microglia can have either a protective or a toxic role, activated microglia may be the result, but also the cause of damage to brain cells.”

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, adds, “It will be important to understand whether this process takes place in a special way in association with the first onset of symptoms or whether inflammation is more generally a process that contributes to worsening of symptoms.”

Because this data suggests that inflammation may contribute to features of the early course of schizophrenia, a new potential avenue of treatment for schizophrenia may be to use anti-inflammatory agents. Although some anti-inflammatory medications have already been studied, with limited success, in schizophrenia patients, a new generation of these drugs that more specifically target activated microglia have yet to be explored.