miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment

Abstract

Major depressive disorder (MDD), is a prevalent mood disorder that associates with differential prefrontal brain expression patterns1. Treatment of MDD includes a variety of biopsychosocial approaches, but in medical practice, antidepressant drugs are the most common treatment for depressive episodes, and not surprisingly, they are among the most prescribed medications in North America2,3. While they are clearly effective, particularly for moderate to severe depressive episodes, there is important variability in how individuals respond to antidepressant treatment. Failure to respond has important individual, economic and social consequences for patients and their families4. Several lines of evidence demonstrate that genes are regulated through the activity of microRNAs (miRNAs), which act as fine–tuners and on–off switches in gene expression patterns5–7. Here we report on complementary studies using postmortem human brain samples, cellular assays and samples from clinical trials of depressed patients, and show that miR-1202, a miRNA specific to primates and enriched in the human brain, is differentially expressed in depressed individuals. Additionally, miR-1202 regulates the expression of the Metabotropic Glutamate Receptor 4 (GRM4) gene and predicts antidepressant response at baseline. These results suggest that miR-1202 is associated with the pathophysiology of depression and is a potential target for novel antidepressant treatments.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…Finally, miR-135a levels in blood and brain of depressed human patients were demonstrated to be lower compared to controls (Issler et al 2014). A recent study including data on humans reported miR-1202 as a promising marker of MDD and antidepressant response (Lopez et al 2014). Interestingly, the tar-gets of miR-1202 are genes involved in neurological processes associated with the pathogenesis of MDD, including the GRM4 gene that has been implicated in the regulation of anxiety-related behaviours (Pilc et al 2008;Davis et al 2012).…”

Peripheral whole blood microRNA alterations in major depression and bipolar disorder

“…Moreover, miR-1202 plasma levels were modulated by antidepressant treatment and correlated with clinical response (Lopez et al, 2014). Finally, a decrease in miR-135, a miRNA regulating serotonergic neuron activity, was found in both post-mortem brains and blood of MD patients (Issler et al, 2014).…”

microRNA-124: a putative therapeutic target and biomarker for major depression

“…Most notably are miR-1202 and miR-135a. MiR-1202 was found to be downregulated in postmortem brain tissue from individuals with major depression [19]. Its level in blood cells can also be used to distinguish selective serotonin reuptake inhibitor responders and nonresponders.…”