Insights into psychosis risk from leukocyte microRNA expression

Dysregulation of immune system functions has been implicated in schizophrenia, suggesting that immune cells may be involved in the development of the disorder. With the goal of a biomarker assay for psychosis risk, we performed small RNA sequencing on RNA isolated from circulating immune cells. We c...

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Vydané v:Translational psychiatry Ročník 6; číslo 12; s. e981
Hlavní autori: Jeffries, C D, Perkins, D O, Chandler, S D, Stark, T, Yeo, E, Addington, J, Bearden, C E, Cadenhead, K S, Cannon, T D, Cornblatt, B A, Mathalon, D H, McGlashan, T H, Seidman, L J, Walker, E F, Woods, S W, Glatt, S J, Tsuang, M
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 13.12.2016
Nature Publishing Group
Predmet:
631/378/340
692/53/2421
692/699/476/1799
Adolescent
Adult
Behavioral Sciences
Biological Psychology
Child
Disease Progression
Down-Regulation - genetics
Female
Gene Expression - genetics
Genetic Predisposition to Disease - genetics
Genetic Testing
Humans
Immune System Phenomena - genetics
Leukocytes - immunology
Longitudinal Studies
Male
Medicine
Medicine & Public Health
MicroRNAs - genetics
Monocytes - immunology
Neurosciences
Original
original-article
Pharmacotherapy
Psychiatry
Psychosis
Psychotic Disorders - genetics
Psychotic Disorders - immunology
Risk Assessment
Schizophrenia - genetics
Schizophrenia - immunology
Schizotypal Personality Disorder - genetics
Schizotypal Personality Disorder - immunology
Young Adult
ISSN:2158-3188, 2158-3188
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Popis
Shrnutí:Dysregulation of immune system functions has been implicated in schizophrenia, suggesting that immune cells may be involved in the development of the disorder. With the goal of a biomarker assay for psychosis risk, we performed small RNA sequencing on RNA isolated from circulating immune cells. We compared baseline microRNA (miRNA) expression for persons who were unaffected ( n =27) or who, over a subsequent 2-year period, were at clinical high risk but did not progress to psychosis ( n =37), or were at high risk and did progress to psychosis ( n =30). A greedy algorithm process led to selection of five miRNAs that when summed with +1 weights distinguished progressed from nonprogressed subjects with an area under the receiver operating characteristic curve of 0.86. Of the five, miR-941 is human-specific with incompletely understood functions, but the other four are prominent in multiple immune system pathways. Three of those four are downregulated in progressed vs. nonprogressed subjects (with weight -1 in a classifier function that increases with risk); all three have also been independently reported as downregulated in monocytes from schizophrenia patients vs. unaffected subjects. Importantly, these findings passed stringent randomization tests that minimized the risk of conclusions arising by chance. Regarding miRNA–miRNA correlations over the three groups, progressed subjects were found to have much weaker miRNA orchestration than nonprogressed or unaffected subjects. If independently verified, the leukocytic miRNA biomarker assay might improve accuracy of psychosis high-risk assessments and eventually help rationalize preventative intervention decisions.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2016.148