Peripheral MicroRNA Signatures in Adolescent Depression

Adolescent depression is linked to enduring maladaptive outcomes, chronic severity of symptoms, and poor treatment response. Identifying epigenetic signatures of adolescent depression is urgently needed to improve early prevention and intervention strategies. MicroRNAs (miRNAs) are epigenetic regulators of adolescent neurodevelopmental processes, but their role as markers and mediators of adolescent depression is unknown.

Here, we examined miRNA profiles from dried blood spot samples of male and female adolescents with clinical depression and psychiatrically healthy male and female adolescents (N = 62). We processed and sequenced these samples using a small RNA protocol tailored for miRNA identification.

We identified 9 differentially expressed (DE) miRNAs (adjusted p value < .05), all of which were upregulated in adolescents with depression. At future follow-ups post blood collection, expression of miR-3613-5p, mir-30c-2, and miR-942-5p were positively associated with depression severity but not anxiety, suggesting a stronger link to persistent depression symptoms. Expression of miR-32-5p inversely correlated with hippocampal volume, highlighting a potential neurobiological basis. Common predicted gene targets of the DE miRNAs are involved in neurodevelopment, cognitive processing, and depressive disorders.

These findings lay the groundwork for identifying adolescent peripheral miRNA markers that reflect neurodevelopmental pathways that shape lifelong psychopathology risk.