Altered expression of microglial markers of phagocytosis in schizophrenia.
Level 4 - case-series / case-control
Case-control post-mortem human tissue study
PubMed 36527956 · doi:10.1016/j.schres.2022.12.005
What was done
Transcript levels of complement components and microglia-specific phagocytic and activation markers were measured using quantitative PCR in prefrontal cortex tissue from 62 matched pairs of individuals with schizophrenia and unaffected comparison subjects (124 human subjects total). To evaluate potential medication confounds, transcript levels were also quantified in antipsychotic-exposed monkeys.
What was found
Relative to comparison subjects, schizophrenia subjects had higher mRNA levels for C4 (+154%), C1q (+69%), and phagocytic markers Axl (+27%), MerTK (+27%), and CD68 (+27%) (all p ≤ .042). Microglial phagocytic transcript levels correlated with C4 mRNA in schizophrenia subjects (all r ≥ 0.31, p ≤ .015). Schizophrenia tissue also showed higher THIK1 mRNA (+30%) and lower P2Y12 mRNA (-27%) (all p ≤ .016). Transcript levels were unchanged in antipsychotic-exposed monkeys.
Why it matters
This study provides evidence that complement elevation in schizophrenia is accompanied by upregulated microglial phagocytic machinery, supporting the hypothesis that complement-mediated microglial engulfment contributes to prefrontal dendritic spine loss.
Limits
The study is post-mortem and observational, measuring transcript levels via qPCR rather than protein levels or functional synaptic engulfment directly. Details on monkey sample size and antipsychotic exposure regimen were not reported in the abstract.
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