miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders

Tsermpini, Evangelia Eirini; Kalogirou, Christina I; Kyriakopoulos, George; Patrinos, George P.; Stathopoulos, Constantinos

doi:10.1038/s41397-022-00283-7

Cited by 12 publications

(8 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, exosomes have been shown to also contain miRNA molecules that can be altered under stress [ 46 ]. Furthermore, several miRNA molecules, for instance miR-34a, miR-106, miR-134, and miR-132, are deregulated in MDD and show brain enrichment in MDD [ 47 , 48 ]. It is therefore possible that, in addition to an inhibition of PLD and a reduction of phosphatidic acid, ceramide also facilitates the uptake of miR-34a, miR-106, miR-134, and miR-132 and other miRNAs into the brain [ 49 ], a mechanism that may contribute to the development of MDD.…”

Section: Discussionmentioning

confidence: 99%

Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma

et al. 2022

View full text Add to dashboard Cite

Major depressive disorder (MDD) is a very common, severe disease with a lifetime prevalence of ~ 10%. The pathogenesis of MDD is unknown and, unfortunately, therapy is often insufficient. We have previously reported that ceramide levels are increased in the blood plasma of patients with MDD and in mice with experimental MDD. Here, we demonstrate that ceramide-enriched exosomes in the blood plasma are increased in mice with stress-induced MDD. Genetic studies reveal that neutral sphingomyelinase 2 is required for the formation of ceramide-enriched exosomes in the blood plasma. Accordingly, induced deficiency of neutral sphingomyelinase 2 prevented mice from the development of stress-induced MDD. Intravenous injection of microparticles from mice with MDD or injection of ceramide-loaded exosomes induced MDD-like behavior in untreated mice, which was abrogated by ex vivo pre-incubation of purified exosomes with anti-ceramide antibodies or ceramidase. Mechanistically, injection of exosomes from mice with MDD or injection of ex vivo ceramide-loaded microparticles inhibited phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus, which has been previously shown to mediate MDD by plasma ceramide. In summary, our data indicate that ceramide-enriched exosomes are released by neutral sphingomyelinase 2 into the blood plasma upon stress and mediate stress-induced MDD. Key messages Stress induces ceramide-enriched exosomes in the blood plasma. Ceramide-enriched exosomes mediate major depressive disorder (MDD). Deficiency of neutral sphingomyelinase 2 protects from stress-induced MDD. Neutralization or digestion of ceramide in exosomes prevents stress-induced MDD. Ceramide-enriched exosomes inhibit endothelial phospholipase D in the hippocampus.

show abstract

Section: Discussionmentioning

confidence: 99%

Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Additional research is needed to identify microRNA expression signatures that link metabolic liver disease with psychiatric disorders. Finally, microRNAs are being explored as potential diagnostic biomarkers and therapeutics for NAFLD/NASH ( Di Mauro et al, 2021 ; Mohamed et al, 2021 ) and myriad psychiatric disorders as well ( Alural et al, 2017 ; Roy et al, 2020 ; Islam et al, 2021 ; Srivastava et al, 2021 ; Tsermpini et al, 2022 ).…”

Section: Mechanistic Synergies Between Non-alcoholic Fatty Liver Dise...mentioning

confidence: 99%

Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines

et al. 2022

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world and one of the leading indications for liver transplantation. It is one of the many manifestations of insulin resistance and metabolic syndrome as well as an independent risk factor for cardiovascular disease. There is growing evidence linking the incidence of NAFLD with psychiatric illnesses such as schizophrenia, bipolar disorder and depression mechanistically via genetic, metabolic, inflammatory and environmental factors including smoking and psychiatric medications. Indeed, patients prescribed antipsychotic medications, regardless of diagnosis, have higher incidence of NAFLD than population norms. The mechanistic pharmacology of antipsychotic-associated NAFLD is beginning to emerge. In this review, we aim to discuss the pathophysiology of NAFLD including its risk factors, insulin resistance and systemic inflammation as well as its intersection with psychiatric illnesses.

show abstract

“…The third largest, and also the most recent, cluster has the following top citing papers: van Calker and Serchov [110] (coverage = 14, GCS = 3), Tsermpini et al [118] (coverage = 11, GCS = 0), and Ghafouri-Fard et al [119] (coverage = 11, GCS = 6). However, the label from this cluster stems from several citing papers that used a bioinformatics approach (e.g., Sabaie et al [120] with a coverage = 8 and GCS = 3, Sabaie et al [121] with a coverage = 7 and GCS = 0, and Jin et al [122] with a coverage = 5 and GCS = 0).…”

Section: Cluster #2: Bioinformatics Analysismentioning

confidence: 99%

Mapping miRNA Research in Schizophrenia: A Scientometric Review

Lim

Carollo

Neoh

et al. 2022

IJMS

View full text Add to dashboard Cite

Micro RNA (miRNA) research has great implications in uncovering the aetiology of neuropsychiatric conditions due to the role of miRNA in brain development and function. Schizophrenia, a complex yet devastating neuropsychiatric disorder, is one such condition that had been extensively studied in the realm of miRNA. Although a relatively new field of research, this area of study has progressed sufficiently to warrant dozens of reviews summarising findings from past to present. However, as a majority of reviews cannot encapsulate the full body of research, there is still a need to synthesise the diversity of publications made in this area in a systematic but easy-to-understand manner. Therefore, this study adopted bibliometrics and scientometrics, specifically document co-citation analysis (DCA), to review the literature on miRNAs in the context of schizophrenia over the course of history. From a literature search on Scopus, 992 papers were found and analysed with CiteSpace. DCA analysis generated a network of 13 major clusters with different thematic focuses within the subject area. Finally, these clusters are qualitatively discussed. miRNA research has branched into schizophrenia, among other medical and psychiatric conditions, due to previous findings in other forms of non-coding RNA. With the rise of big data, bioinformatics analyses are increasingly common in this field of research. The future of research is projected to rely more heavily on interdisciplinary collaboration. Additionally, it can be expected that there will be more translational studies focusing on the application of these findings to the development of effective treatments.

show abstract

miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders

Cited by 12 publications

References 103 publications

Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma

Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma

Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines

Mapping miRNA Research in Schizophrenia: A Scientometric Review

Contact Info

Product

Resources

About