Available data indicate that the immune system helps coordinate portions of the central nervous system. It has been hypothesized that microglia, the brain’s resident immune cells, acquire a pro-inflammatory profile and contribute to the generation of an inflammatory milieu by releasing cytokines and reactive oxygen species. Additionally, neuroinflammation appears to be one of the common hallmarks in various neuropsychiatric disorders, and has previously been implicated in the pathophysiology of schizophrenia.
A new study conducted by a team of investigators affiliated with the University of Toronto provides evidence to the contrary, and findings indicate that microglial activation is not present in untreated patients diagnosed with first-episode psychosis. These findings were published in The American Journal of Psychiatry.1
Similarly, in a recent unrelated study, Dutch investigators reported no significant difference in microglial activation across various brain regions between patients with recent onset psychosis and control participants. Their findings were published in NPJ Schizophrenia.2
Investigators in both studies used positron emission tomography (PET) to assess neuroinflammation within the brain parenchyma. It is known that microglial activation is associated with increased 18kDa translocator protein (TSPO) expression. The Canadian researchers used a novel second-generation TSPO PET radioligand [18F]FEPPA to evaluate microglial activation in the dorsolateral prefrontal cortex and hippocampus,1 whereas the team from the Netherlands used a (R)-[11C]PK11195 PET tracer to measure TSPO levels in the frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus.2
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In the first study, only first-episode psychosis patients diagnosed with schizophrenia, schizophreniform disorder, delusional disorder, or psychosis were eligible to participate. All 19 first-episode psychosis patients were either antipsychotic medication free or antipsychotic medication naive.1 In the second study, only patients with a recent onset psychosis were included in the study; however, 15 out of 19 patients were taking antipsychotic medication at the time of the study.2
Results indicate that there is no evidence of increased microglial activation as measured by [18F]FEPPA binding in the dorsolateral prefrontal cortex and hippocampus in patients with first episode psychosis compared with that of typical, healthy control participants.1 Similarly, there is no evidence of increased microglial activation as measured by (R)-[11C]PK11195 binding in five different brain regions in recent onset psychosis patients compared with that of controls.2
The Dutch investigators noted that antipsychotic treatment may factor into their findings, but the Canadian investigators did not find evidence of increased microglial activation in antipsychotic medication free or antipsychotic medication naive patients either. Thus, “Neuroinflammatory processes may take place earlier in the course of schizophrenia, such as during the clinical high-risk state of psychosis, or may be present only in a subpopulation of patients,” the Canadian authors concluded.1
1. Hafizi S, Tseng HH, Rao N, et al. Imaging microglial activation in untreated first-episode psychosis: a PET study with [18F]FEPPA. Am J Psychiatry. 2016. doi: 10.1176/appi.ajp.2016.16020171.
2. van der Doef TF, de Witte LD, Sutterland AL, et al. In vivo (R)-[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. NPJ Schizophr. 2016;2:16031.