Microglial activation in schizophrenia: Is translocator 18 kDa protein (TSPO) the right marker?

Area of Science:

• Neuroscience
• Psychiatry
• Molecular Imaging

Background:

• Positron emission tomography (PET) with translocator 18 kDa protein (TSPO) radioligands is commonly used to assess microglial activation in schizophrenia.
• The specificity of TSPO as a marker for activated microglia in vivo is under increasing scrutiny.

Purpose of the Study:

• To evaluate the expression and specificity of TSPO in the context of schizophrenia.
• To determine if TSPO is a reliable marker for microglial activation in schizophrenia.

Main Methods:

• Analysis of TSPO expression in postmortem brain tissue from schizophrenia patients.
• Correlation analysis between TSPO expression and known microglial activation markers.
• Investigation of TSPO expression in isolated human primary microglia, both in resting and activated states.

Main Results:

• TSPO expression was not elevated in postmortem brain tissue of schizophrenia patients.
• TSPO expression did not correlate with established microglial activation markers.
• TSPO expression was found in cells other than microglia and was not upregulated in activated human primary microglia.
• Findings align with recent reports questioning TSPO's role as a specific marker for activated microglia in schizophrenia.

Conclusions:

• TSPO is not a reliable or specific marker for microglial activation in schizophrenia.
• Current TSPO-based PET imaging may not accurately reflect microglial activation states in schizophrenia.
• Further development of novel positron emission tomography tracers is crucial for studying microglial activation in schizophrenia and other neurological disorders.