Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical...

Area of Science:

• Neuroimmunology
• Psychiatric disorders
• Innate immunity

Background:

• Schizophrenia (SZ) is associated with innate immune system activation.
• Toll-like receptors (TLRs) and the complement system are key components of innate immunity implicated in SZ.
• TLRs recognize various pathogen-associated molecular patterns, including bacterial (TLR1, TLR4) and viral (TLR3, TLR8) molecules.

Purpose of the Study:

• To compare peripheral mRNA levels of TLR1, TLR3, TLR4, and TLR8 between individuals with schizophrenia (SZ) and healthy controls (HC).
• To investigate the relationship between TLRs, immune activation (complement expression), and brain structure (cingulate gyrus cortical thickness) in SZ.
• To explore potential differences in bacterial versus viral immune influence in schizophrenia.

Main Methods:

• Peripheral blood white blood cells were collected from 86 SZ and 77 HC individuals.
• mRNA levels of TLR1, TLR3, TLR4, TLR8, and complement receptors were quantified.
• Structural MRI scans were performed on a subset of participants to measure cortical thickness.

Main Results:

• Individuals with SZ exhibited significantly higher TLR4 and TLR8 mRNA levels and lower TLR3 mRNA levels compared to HC.
• TLR and complement factor expression were significantly associated in both SZ and HC groups.
• Elevated TLR mRNA levels, particularly TLR4 and TLR8, were observed in SZ individuals with higher complement expression.
• Inverse associations were found between TLR mRNA levels and cingulate gyrus cortical thickness in both SZ and HC groups.

Conclusions:

• The findings support a coordinated role of Toll-like receptors and the complement system in the innate immune activation observed in schizophrenia.
• The observed TLR expression patterns suggest a potentially greater bacterial than viral immune system influence in schizophrenia.
• Specific TLRs are linked to reductions in cortical thickness within brain regions like the cingulate gyrus, highlighting a neurobiological connection.