Circulating microRNA Profiles Identify a Patient Subgroup with High Inflammation and Severe Symptoms in Schizophrenia

Takuya Miyano1, Tsuyoshi Mikkaichi1, Kouichi Nakamura1

  • 1Translational Science Department II, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa, Tokyo 140-8710, Japan.

Insights

MicroRNAs (miRNAs) in blood can identify schizophrenia subgroups with high inflammation. This finding offers potential for precision medicine targeting inflammatory pathways in schizophrenia patients.

Area of Science:

  • Neuroscience
  • Biomarkers
  • Psychiatry

Background:

  • Schizophrenia is a complex psychiatric disorder with heterogeneous pathophysiology.
  • Current biomarkers for schizophrenia lack specificity and do not fully capture disease heterogeneity.
  • Understanding molecular differences can lead to personalized treatment strategies.

Purpose of the Study:

  • To investigate circulating microRNAs (miRNAs) as potential biomarkers for stratifying schizophrenia patients.
  • To explore the pathophysiological basis of schizophrenia heterogeneity using molecular profiling.
  • To identify patient subgroups with distinct inflammatory profiles.

Main Methods:

  • Plasma samples from schizophrenia patients experiencing acute psychosis were analyzed.
  • Levels of 179 miRNAs and 378 proteins were quantified.
  • miRNA and protein expression data were correlated with Positive and Negative Syndrome Scale (PANSS) scores.
  • miRNA and protein set enrichment analyses were performed.

Main Results:

  • Plasma miRNA profiles identified three distinct schizophrenia subgroups.
  • One subgroup exhibited higher PANSS scores and four downregulated miRNAs.
  • These miRNAs were linked to the regulation of key inflammatory cytokines (IL-1β, IL-6, TNFα).
  • The same subgroup showed 22 upregulated proteins, primarily pro-inflammatory cytokines, enriching 'Cytokine-cytokine receptor interaction' pathways.
  • This subgroup is inferred to have a heightened inflammatory state.

Conclusions:

  • Circulating miRNAs can serve as biomarkers reflecting schizophrenia symptoms and underlying pathophysiology.
  • A subgroup of schizophrenia patients with elevated inflammation was identified.
  • These findings support the development of precision medicine approaches, including anti-inflammatory treatments, for specific schizophrenia patient subgroups.