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Updated: Jun 27, 2025

Cerebrospinal Fluid MicroRNA Profiling Using Quantitative Real Time PCR
Published on: January 22, 2014
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.
Abstract:
Schizophrenia is a complex and heterogenous psychiatric disorder. This study aimed to demonstrate the potential of circulating microRNAs (miRNAs) as a clinical biomarker to stratify schizophrenia patients and to enhance understandings of their heterogenous pathophysiology. We measured levels of 179 miRNA and 378 proteins in plasma samples of schizophrenia patients experiencing acute psychosis and obtained their Positive and Negative Syndrome Scale (PANSS) scores. The plasma miRNA profile revealed three subgroups of schizophrenia patients, where one subgroup tended to have higher scores of all the PANSS subscales compared to the other subgroups. The subgroup with high PANSS scores had four distinctively downregulated miRNAs, which enriched 'Immune Response' according to miRNA set enrichment analysis and were reported to negatively regulate IL-1β, IL-6, and TNFα. The same subgroup had 22 distinctively upregulated proteins, which enriched 'Cytokine-cytokine receptor interaction' according to protein set enrichment analysis, and all the mapped proteins were pro-inflammatory cytokines. Hence, the subgroup is inferred to have comparatively high inflammation within schizophrenia. In conclusion, miRNAs are a potential biomarker that reflects both disease symptoms and molecular pathophysiology, and identify a patient subgroup with high inflammation. These findings provide insights for the precision medicinal strategies for anti-inflammatory treatments in the high-inflammation subgroup of schizophrenia.
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.
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