MicroRNA regulation of prefrontal cortex development and psychiatric risk in adolescence

Abstract

In this review, we examine the role of microRNAs in the development of the prefrontal cortex (PFC) in adolescence and in individual differences in vulnerability to mental illness. We describe results from clinical and preclinical research indicating that adolescence coincides with drastic changes in local microRNA expression, including microRNAs that control gene networks involved in PFC and cognitive refinement. We highlight that altered levels of microRNAs in the PFC are associated with psychopathologies of adolescent onset, notably depression and schizophrenia. We show that microRNAs can be measured non-invasively in peripheral samples and could serve as longitudinal physiological readouts of brain expression and psychiatric risk in youth.

Keywords: Biomarkers; DCC receptors; Depression; MiR-218; Resilience; Schizophrenia; Vulnerability.

Fig. 1.

Number of articles published in the topic of biomarkers for psychiatric risk according to searches using Scopus ® Elsevier B.V. (A) Using keywords “biomarker” and “psychiatry” yields a track record, as of February 2021, from the year 1989 with ~ 500 articles added per year in the last two decades. (B) Using the keywords “biomarker”, “psychiatry” and “adolescence” to the search shows a track record from the year 2000 with only ~80 articles published annually in the last 6 years.

Fig. 2.

Peripheral microRNAs in adolescence as indicators of neurodevelopmental state and psychiatric risk. Assessment of microRNA profiles in peripheral samples from adolescent boys and girls in longitudinal studies could (i) help identifying markers of risk and resilience, (ii) guide prevention and intervention programs specifically for this age, and (ii) allow monitoring of disease severity.