The Role of microRNA Expression in Cortical Development During Conversion to Psychosis

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2017-10, Vol.42 (11), p.2188-2195
• Main Authors: Zheutlin, Amanda B, Jeffries, Clark D, Perkins, Diana O, Chung, Yoonho, Chekroud, Adam M, Addington, Jean, Bearden, Carrie E, Cadenhead, Kristin S, Cornblatt, Barbara A, Mathalon, Daniel H, McGlashan, Thomas H, Seidman, Larry J, Walker, Elaine F, Woods, Scott W, Tsuang, Ming, Cannon, Tyrone D
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Algorithms; Brain; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cohort Studies; Conversion; Cortex; Cytokines; Cytokines - metabolism; Developmental plasticity; Female; Gene expression; Gene Expression Regulation, Developmental - physiology; Health risks; Humans; Immune response; Inflammation; Intracellular; Intracellular signalling; Leukocytes; Leukocytes - metabolism; Leukocytes - pathology; Macrophages; Male; Mental disorders; Microglia; Microglia - metabolism; MicroRNAs; MicroRNAs - classification; MicroRNAs - metabolism; miRNA; Original; Predictive Value of Tests; Prodromal Symptoms; Psychosis; Psychotic Disorders - pathology; Risk groups; Schizophrenia; Signal transduction; Substantia grisea; Synaptic plasticity; Synaptogenesis; Thinning; Young Adult
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2017.34

In a recent report of the North American Prodrome Longitudinal Study (NAPLS), clinical high-risk individuals who converted to psychosis showed a steeper rate of cortical gray matter reduction compared with non-converters and healthy controls, and the rate of cortical thinning was correlated with levels of proinflammatory cytokines at baseline. These findings suggest a critical role for microglia, the resident macrophages in the brain, in perturbations of cortical maturation processes associated with onset of psychosis. Elucidating gene expression pathways promoting microglial action prior to disease onset would inform potential preventative intervention targets. Here we used a forward stepwise regression algorithm to build a classifier of baseline microRNA expression in peripheral leukocytes associated with annualized rate of cortical thinning in a subsample of the NAPLS cohort (N=74). Our cortical thinning classifier included nine microRNAs, p=3.63 × 10 , R =0.358, permutation-based p=0.039, the gene targets of which were enriched for intracellular signaling pathways that are important to coordinating inflammatory responses within immune cells (p