Peripheral levels of the micro-RNA miR-1202 are correlated with changes in brain activity and connectivity during an antidepressant treatment

Abstract

IntroductionMicro-RNAs are short non-coding sequences playing a major role in regulating gene expression. Peripheral levels of the micro-RNA miR-1202 have been shown to predict antidepressant response and to change during treatment. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo.ObjectivesWe aimed at investigating a potential link between peripheral micro-RNA and neuroimaging measures.MethodsAt baseline and after 8 weeks of desvenlafaxine (50–100 mg die), twenty depressed patients were scanned with 3 T magnetic resonance imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition. Blood samples were taken for RNA extraction.ResultsDuring resting state, baseline miR-1202 levels were predictive of decreased connectivity between the posterior cingulate and the prefrontal, occipital and parietal cortices. Changes in miR-1202 levels were correlated with changes in activity in right precuneus within the default-mode network, and with decreased connectivity between the posterior cingulate and the temporal and prefrontal cortices, and the precuneus. During the Go/NoGo task, baseline levels and changes in these levels were correlated with activity changes in different regions, including bilateral prefrontal, insular, cingulate, and temporal cortices. Finally, secondary analyses suggest an association between miR-1202 levels and glutamate levels measured by spectroscopy in dorsomedial prefrontal cortex.ConclusionsThis is the first study showing that baseline and changes in peripheral levels of one micro-RNA were associated with changes in brain activity and connectivity during an antidepressant treatment. MiR-1202 may act through the modulation of the glutamatergic system.