Urinary exosomal microRNAs as predictive biomarkers for persistent psychotic-like experiences

Abstract

Psychotic-like experiences (PLEs) occur occasionally in adolescence and mostly disappear with increasing age. Their presence, if persistent, is considered a robust risk factor for subsequent psychiatric disorders. To date, only a few biological markers have been investigated for persistent PLE prediction. This study identified urinary exosomal microRNAs that can serve as predictive biomarkers for persistent PLEs. This study was part of a population-based biomarker subsample study of the Tokyo Teen Cohort Study. A total of 345 participants aged 13 (baseline) and 14 (follow-up) years underwent PLE assessments by experienced psychiatrists using semi-structured interviews. We defined remitted and persistent PLEs based on longitudinal profiles. We obtained urine at baseline and the expression levels of urinary exosomal miRNAs were compared between 15 individuals with persistent PLEs and 15 age- and sex-matched individuals with remitted PLEs. We constructed a logistic regression model to examine whether miRNA expression levels could predict persistent PLEs. We identified six significant differentially expressed microRNAs, namely hsa-miR-486-5p, hsa-miR-199a-3p, hsa-miR-144-5p, hsa-miR-451a, hsa-miR-143-3p, and hsa-miR-142-3p. The predictive model showed an area under the curve of 0.860 (95% confidence interval: 0.713–0.993) for five-fold cross-validation. We found a subset of urinary exosomal microRNAs that were differentially expressed in persistent PLEs and presented the likelihood that a microRNA-based statistical model could predict them with high accuracy. Therefore, urine exosomal miRNAs may serve as novel biomarkers for the risk of psychiatric disorders.

The role of Extracellular Genomic Materials (EGMs) in psychiatric disorders

“…Apart from these studies conducted on schizophrenia spectrum disorders, in a recent study by Tomita et al identified six urinary exosome miRNAs expressed differently in persistent psychotic-like experiences. This study prompts that urine exosome miRNAs might be used as novel biomarkers [ 100 ].…”

MicroRNA expression profiling of urine exosomes in children with congenital cytomegalovirus infection

“…As exosomes can penetrate the blood–brain barrier and circulate throughout the body, serum exosomes may be ideal markers for neuronal diseases. There have been many reports on serum exosomes 7 , 10 ; however, research on urinary exosomes for neuronal diseases is limited 11 , 12 , 15 . Tomita et al 12 identified exosomal miRNAs in urine as risk factors for psychiatric disorders.…”

“…There have been many reports on serum exosomes 7 , 10 ; however, research on urinary exosomes for neuronal diseases is limited 11 , 12 , 15 . Tomita et al 12 identified exosomal miRNAs in urine as risk factors for psychiatric disorders. They discovered that the expressions of six miRNAs (hsa-miR-486-5p, hsa-miR-199a-3p, hsa-miR-144-5p, hsa-miR-451a, hsa-miR-143-3p, and hsa-miR-142-3p) were elevated in the persistent psychotic-like experience group compared to the remitted group 12 .…”

“…Tomita et al 12 identified exosomal miRNAs in urine as risk factors for psychiatric disorders. They discovered that the expressions of six miRNAs (hsa-miR-486-5p, hsa-miR-199a-3p, hsa-miR-144-5p, hsa-miR-451a, hsa-miR-143-3p, and hsa-miR-142-3p) were elevated in the persistent psychotic-like experience group compared to the remitted group 12 . These results suggest that urine exosomal miRNAs are potential biomarkers for neurological disorders.…”

“…Exosomes can cross the blood–brain barrier bidirectionally 10 , and a growing number of reports have shown a relationship between neurological disorders and peripheral exosomes. Although most of these studies have investigated blood exosomes, urine exosomes have also been analyzed in some studies 11 , 12 . Urine samples have the advantage that urine collection is usually non-invasive, and the amount of sample required for the assay is small.…”