Gene expression profiling in whole blood stimulated ex vivo with lipopolysaccharide as a tool to predict post‐stroke depressive symptoms: Proof‐of‐concept study

Prediction of post-stroke depressive symptoms (DSs) is challenging in patients without a history of depression. Gene expression profiling in blood cells may facilitate the search for biomarkers. The use of an ex vivo stimulus to the blood helps to reveal differences in gene profiles by reducing variation in gene expression. We conducted a proof-of-concept study to determine the usefulness of gene expression profiling in lipopolysaccharide (LPS)-stimulated blood for predicting post-stroke DS. Out of 262 enrolled patients with ischemic stroke, we included 96 patients without a pre-stroke history of depression and not taking any anti-depressive medication before or during the first 3 months after stroke. We assessed DS at 3 months after stroke using the Patient Health Questionnaire-9. We used RNA sequencing to determine the gene expression profile in LPS-stimulated blood samples taken on day 3 after stroke. We constructed a risk prediction model using a principal component analysis combined with logistic regression. We diagnosed post-stroke DS in 17.7% of patients. Expression of 510 genes differed between patients with and without DS. A model containing 6 genes (PKM, PRRC2C, NUP188, CHMP3, H2AC8, NOP10) displayed very good discriminatory properties (area under the curve: 0.95) with the sensitivity of 0.94 and specificity of 0.85. Our results suggest the potential utility of gene expression profiling in whole blood stimulated with LPS for predicting post-stroke DS. This method could be useful for searching biomarkers of post-stroke depression.