miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment
Open accessAbstract
Major depressive disorder (MDD) is a prevalent mood disorder that is associated with differential prefrontal brain expression patterns. Treatment of MDD includes a variety of biopsychosocial approaches. In medical practice, antidepressant drugs are the most common treatment for depressive episodes, and they are among the most prescribed medications in North America. Although antidepressants are clearly effective, particularly for moderate to severe depressive episodes, there is variability in how individuals respond to antidepressant treatment. Failure to respond has individual, economic and social consequences for patients and their families. Several lines of evidence demonstrate that genes are regulated through the activity of microRNAs (miRNAs), which act as fine-tuners and on-off switches of gene expression. Here we report on complementary studies using postmortem human brain samples, cellular assays and samples from clinical trials of patients with depression and show that miR-1202, a miRNA specific to primates and enriched in the human brain, is differentially expressed in individuals with depression. Additionally, miR-1202 regulates expression of the gene encoding metabotropic glutamate receptor-4 (GRM4) 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 new antidepressant treatments.
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Upon antidepressant treatment, peripheral levels of miR-1202 increased after 8 weeks of treatment.
“Additionally, upon antidepressant treatment, peripheral levels of miR-1202 increased after 8 weeks of treatment”
From Epigenetics and depression (2019) · cites this paper as [30]
The passage on blood miR-1202 levels (labeled Abstract in our copy) reports an increase after eight weeks of citalopram treatment in patients whose depression remitted. It reports no such change in nonresponders, so the unqualified claim overgeneralizes the finding. (LLM, conf=0.90)
Experimental — accuracy not yet measuredmiR-1202, a miRNA regulating GRM4, was downregulated in the prefrontal cortex of MDD patients who died by suicide compared with psychiatrically healthy controls.
“miR-1202, a miRNA regulating a glutamate receptor ( GRM4 ) was found to be downregulated in PFC of MDD patients who died by suicide compared with psychiatrically healthy controls.”
From Epigenetics and depression (2019) · cites this paper as [30]
The passage on the independent PFC sample (indexed under Abstract; page unavailable) reports lower miR-1202 in depressed subjects than controls, and the paper states that miR-1202 regulates GRM4. The Methods > Human Samples passage (page unavailable) describes postmortem cases and controls but does not establish that the depressed subjects in that comparison all died by suicide. The suicide qualifier is therefore not supported for the reported comparison. (LLM, conf=0.83)
Experimental — accuracy not yet measuredmiR-335, miR-1202, miR-29b-3p, and miR-134-5p may regulate depression through inhibiting GRM4 expression, affecting Ca2+ influx into prefrontal cortex neurons and extracellular glutamate concentration.
“MiR-335, miR-1202, miR-29b-3p, and miR-134-5p may regulate depression through inhibiting the expression of GRM4 gene (Fig. 5), that in turn affect the influx of Ca2+ into the prefrontal cortex neurons and the extracellular concentration of glutamate.277–283”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [281]
The paper’s main text (indexed under Abstract; no page number available) reports that miR-1202 reduces GRM4 expression in a cell experiment and that their expression is inversely correlated in prefrontal cortex tissue from depressed individuals. It does not establish GRM4 inhibition by the other three named miRNAs or the proposed effects on neuronal Ca2+ influx and extracellular glutamate concentration. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHigher miR-1202 levels in MDD patients are reported following eight weeks of citalopram, but no differences in controls.
“Higher miR-1202 levels in MDD patients are reported following eight weeks of citalopram, but no differences in controls.281”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [281]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredmRNA levels of GRM4 increased in both cohorts.
“Correspondingly, mRNA levels of GRM4 increased in both cohorts.”
From Epigenetics and depression (2019) · cites this paper as [30]
The miR-1202 downregulation was replicated in two independent cohorts.
“This was further replicated in two independent cohorts.”
From Epigenetics and depression (2019) · cites this paper as [30]
miR-1202 has consistently been reported to be associated with treatment response to antidepressants using the candidate approach.
“In addition, we found that miR-1202, which has consistently been reported to be associated with treatment response to antidepressants using the candidate approach [46,50], was also correlated with treatment response based on our genome-wide approach.”
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References 33 · Cited by 308
- Authors
- Lopez, J. P., Lim, R., Cruceanu, C., Crapper, L., Fasano, C., Labonte, B., Maussion, G., Yang, J. P., Yerko, V., Vigneault, E., El Mestikawy, S., Mechawar, N., Pavlidis, P., & Turecki, G.
- Affiliations
- University of British Columbia (CA)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Turecki, Gustavo
- ORCID
- Venue
- Nature Medicine
- Published
- 2014-06-08
- Volume
- 20
- Issue
- 7
- Pages
- 764-768
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4087015
- OpenAlex
- W2085788459
- Cited by
- 308
- References
- 33
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 19 · 2023: 20 · 2022: 27 · 2021: 25 · 2020: 23 · 2019: 27 · 2018: 25 · 2017: 32 · 2016: 36 · 2015: 29 · 2014: 8
- FWCI
- 25.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Fondation Brain Canada
- Innovative Research Group Project of the National Natural Science Foundation of China
- Canadian Institutes of Health Research (93775_2, 111260_1, 93775_1)
- Fonds de Recherche du Québec - Santé
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- microRNA, major depressive disorder, antidepressant response, antidepressant resistance, mGluR4, postmortem brain, gene expression regulation, depression pathophysiology, antidepressant targets
- MeSH terms
- Antidepressive Agents, Brain, Cell Line, Major Depressive Disorder, Humans, MicroRNAs
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