Peripheral blood miR-16-5p as a potential biomarker for distinguishing unmedicated bipolar disorder type II from major depressive disorder
Abstract
Objective major depressive disorder (MDD) and bipolar disorder type II (BD-II) are difficult to distinguish clinically due to similar depressive symptoms and unrecognizable hypomania symptoms in the early stages. The study aims to identify these two disorders in the early stages through differential expression of microRNAs.Methods 93 subjects including 66 unmedicated patients (33 MDD, 33 BD-II), and 27 healthy controls (HC) were enrolled. At the time of enrollment, all subjects' demographic data, HAMD, HCL-32, and YMRS scales were assessed. 5 ml of peripheral blood for all subjects was collected for microRNA second-generation sequencing. MicroRNA differential expression, target gene GO and KEGG analyses were performed.Results No statistical differences in demographic data were found except for age (BD-II < MDD, P = 0.002). In terms of clinical data, there are differences in the course of the disease (BD-II > MDD, P = 0.037) and the HCL-32 (BD-II > MDD, P < 0.01). A variance analysis of microRNA expressions across all three groups identified eight highly expressed differential miRNAs (P < 0.001), Pairwise comparisons revealed that the expression level of miR-16-5p was lower in both MDD group (P < 0.05) and BD-II group (P < 0.001) than in HC group, and it was even lower in BD-II group compared to MDD group (P < 0.01). The area under the curve (AUC) for miR-16-5p in differentiating BD-II from MDD groups was 0.723 (P = 0.003).Conclusions Peripheral blood miR-16-5p may serve as a potential biomarker for distinguishing unmedicated BD-II from MDD patients.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
miR-16-5p is reduced in peripheral blood of individuals with MDD and BD.
“miR-16-5p is reduced in peripheral blood of individuals with MDD and BD”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [36]
Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714 · see citing works
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139 · see citing works
Molecular pathways of major depressive disorder converge on the synapse
Fries, G. R., Saldana, V. A., Finnstein, J., & Rein, T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01806-1 · Cited by 504 · see citing works
MiR-16 Targets the Serotonin Transporter: A New Facet for Adaptive Responses to Antidepressants
Baudry, A., Mouillet-Richard, S., Schneider, B., Launay, J.-M., & Kellermann, O. (2010) · Science · doi:10.1126/science.1193692 · Cited by 480 · see citing works
Smalheiser, N. R., Lugli, G., Rizavi, H. S., Torvik, V. I., Turecki, G., & Dwivedi, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033201 · Cited by 324 · see citing works
Almeida, J., & Phillips, M. L. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.010 · Cited by 274 · see citing works
Peripheral whole blood microRNA alterations in major depression and bipolar disorder
Maffioletti, E., Cattaneo, A., Rosso, G., Maina, G., Maj, C., Gennarelli, M., Tardito, D., & Bocchio-Chiavetto, L. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.04.021 · Cited by 181 · see citing works
Epigenetic mechanisms of major depression: Targeting neuronal plasticity
Uchida, S., Yamagata, H., Seki, T., & Watanabe, Y. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12621 · Cited by 181 · see citing works
The bipolar spectrum—the shaping of a new paradigm in psychiatry
Akiskal, H. S. (2002) · Current Psychiatry Reports · doi:10.1007/s11920-002-0001-1 · Cited by 115 · see citing works
Song, M.-F., Dong, J., Wang, Y.-W., He, J., Ju, X., Zhang, L., Zhang, Y., Shi, J., & Lv, Y.-Y. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.02.022 · Cited by 111 · see citing works
Wang, G., An, T., Lei, C., Zhu, X., Yang, L., Zhang, L., & Zhang, R. (2022) · Journal of Ginseng Research · doi:10.1016/j.jgr.2021.03.005 · Cited by 101 · see citing works
Self-citationExploiting Circulating MicroRNAs as Biomarkers in Psychiatric Disorders
Roy, B., Yoshino, Y., McKibben, L. A., Prall, K., Schell, G., & Dwivedi, Y. (2020) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-020-00464-9 · Cited by 95 · see citing works
Altered miRNA expression network in locus coeruleus of depressed suicide subjects
Roy, B., Wang, Q., Palkovits, M., Faludi, G., & Dwivedi, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-04300-9 · Cited by 86 · see citing works
Azevedo, J. A., Carter, B. S., Meng, F., Turner, D. L., Dai, M., Schatzberg, A. F., Barchas, J. D., Jones, E. G., Bunney, W. E., Myers, R., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.07.012 · Cited by 79 · see citing works
Circulating microRNA 134 sheds light on the diagnosis of major depressive disorder
Zhang, H., Liu, X., Chen, J., Cheng, K., Bai, S., Zheng, P., Zhou, C., Wang, W., Wang, H., Zhong, L., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0773-2 · Cited by 73 · see citing works
Fiori, L. M., Lopez, J. P., Richard-Devantoy, S., Berlim, M., Chachamovich, E., Jollant, F., Foster, J., Rotzinger, S., Kennedy, S. H., & Turecki, G. (2017) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx034 · Cited by 71 · see citing works
Muhammad, R. N., Ahmed, L. A., Abdelsalam, R. M., Ahmed, K. A., & Attia, A. S. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01140-4 · Cited by 68 · see citing works
New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview
Bortolozzi, A. A., Fico, G., Berk, M., Solmi, M., Fornaro, M., Quevedo, J., Zarate, C. A., Kessing, L. V., Vieta, E., & Carvalho, A. F. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000007 · Cited by 63 · see citing works
Epigenetic mechanisms in mood disorders: Targeting neuroplasticity
Fass, D. M., Schroeder, F. A., Perlis, R. H., & Haggarty, S. J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.041 · Cited by 62 · see citing works
Serum miRNA as a possible biomarker in the diagnosis of bipolar II disorder
Lee, S.-Y., Lu, R., Wang, L., Chang, C., Lu, T., Wang, T., & Tsai, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-58195-0 · Cited by 56 · see citing works
Bauer, M. S. (2022) · Annals of Internal Medicine · doi:10.7326/aitc202207190 · Cited by 51 · see citing works
MicroRNA dysregulation in manic and euthymic patients with bipolar disorder
Camkurt, M. A., Karababa, İ. F., Erdal, M. E., Kandemir, S. B., Fries, G. R., Bayazıt, H., Ay, M. E., Kandemır, H., Ay, Ö. İ., Coşkun, S., et al. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.09.060 · Cited by 47 · see citing works
Kim, H. K., Tyryshkin, K., Elmi, N., Dharsee, M., Evans, K., Good, J. L., Javadi, M., McCormack, S., Vaccarino, A. L., Zhang, X., et al. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.12.007 · Cited by 46 · see citing works
Self-citationKim, Y., Zhang, Y., Pang, K., Kang, H., Park, H., Lee, Y., Lee, B., Lee, H., Kim, W.-K., Geum, D., et al. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.6.296 · Cited by 43 · see citing works
Meyer, T. D., Bernhard, B., Born, C., Fuhr, K., Gerber, S., Schaerer, L., Langosch, J. M., Pfennig, A., Sasse, J., Scheiter, S., et al. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.07.003 · Cited by 42 · see citing works
D’Addario, C., Palazzo, M. C., Benatti, B., Grancini, B. M., Pucci, M., Francesco, A. D., Camuri, G., Galimberti, D., Fenoglio, C., Scarpini, E. A., et al. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.08.011 · Cited by 42 · see citing works
Żurawek, D., Kuśmider, M., Faron‐Górecka, A., Gruca, P., Pabian, P., Kolasa, M., Solich, J., Szafran‐Pilch, K., Papp, M., & Dziedzicka‐Wasylewska, M. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.11.013 · Cited by 38 · see citing works
Shao, Q.-Y., You, F., Zhang, Y., Hu, L., Liu, W., Liu, Y., Li, J., Wang, S., & Song, M.-F. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.06.034 · Cited by 37 · see citing works
Jiang, X., Wang, X., Jia, L., Sun, T., Kang, J., Zhou, Y., Wei, S., Wu, F., Kong, L., Wang, F., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.09.133 · Cited by 36 · see citing works
Zhao, Y., Chen, Y., Guo, C., Li, P., Cheng, Z., Zheng, L., Sha, B., Xu, H., Su, X., & Wang, Y. (2024) · Theranostics · doi:10.7150/thno.92676 · Cited by 36 · see citing works
Gečys, D., Dambrauskienė, K., Šimonytė, S., Patamsytė, V., Vilkevičiūtė, A., Musneckis, A., Butkutė-Šliuožienė, K., Lesauskaitė, V., Žemaitis, L., Ūsaitė, D., et al. (2022) · Disease Markers · doi:10.1155/2022/3004338 · Cited by 34 · see citing works
Dysregulation of miR-499, miR-708 and miR-1908 during a depression episode in bipolar disorders
Banach, E., Dmitrzak‐Węglarz, M., Pawlak, J., Kapelski, P., Szczepankiewicz, A., Rajewska‐Rager, A., Słopień, A., Skibińska, M., Czerski, P. M., & Hauser, J. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.06.019 · Cited by 33 · see citing works
Comparison of bipolar disorder type II and major depressive disorder
Miola, A., Tondo, L., Pinna, M., Contu, M., & Baldessarini, R. J. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.11.039 · Cited by 32 · see citing works
Valvassori, S. S., Dal-Pont, G. C., Varela, R. B., Resende, W. R., Gava, F. F., Mina, F., Budni, J., & Quevedo, J. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.12.190 · Cited by 31 · see citing works
Malhi, G. S., Outhred, T., & Irwin, L. (2019) · The Canadian Journal of Psychiatry · doi:10.1177/0706743719847341 · Cited by 30 · see citing works
Bipolar disorder type II revisited
FRANCES, A. J., & Jones, K. D. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01038.x · Cited by 27 · see citing works
Almeida, H., Mitjans, M., Arias, B., Vieta, E., Ríos, J., & Benabarre, A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.07.033 · Cited by 25 · see citing works
Panizzutti, B., Bortolasci, C. C., Spolding, B., Kidnapillai, S., Connor, T., Richardson, M. F., Truong, T. T. T., Liu, Z. S.-J., Morris, G., Gray, L. J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137164 · Cited by 25 · see citing works
Chen, Y., Shi, J., Liu, H., Wang, Q., Chen, X., Tang, H., Yan, R., Yao, Z., & Lü, Q. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00757 · Cited by 24 · see citing works
Kidnapillai, S., Wade, B., Bortolasci, C. C., Panizzutti, B., Spolding, B., Connor, T., Crowley, T. M., Jamain, S., Gray, L. J., Leboyer, M., et al. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881119895534 · Cited by 23 · see citing works
A Comprehensive Review on the Role of Non-Coding RNAs in the Pathophysiology of Bipolar Disorder
Ghafouri‐Fard, S., Badrlou, E., Taheri, M. N., Dürsteler, K. M., Brühl, A. B., Bahmani, D. S., & Brand, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105156 · Cited by 23 · see citing works
Squassina, A., Niola, P., López, J. P., Cruceanu, C., Pisanu, C., Congiu, D., Severino, G., Ardau, R., Chillotti, C., Alda, M., et al. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.03.005 · Cited by 21 · see citing works
Menezes, I. C., Baes, C. V. W., Fígaro-Drumond, F. V., Macedo, B. B. D., Bueno, A. C., Lacchini, R., Mello, M. F., de Castro, M., & Juruena, M. F. (2022) · Brain Sciences · doi:10.3390/brainsci12111476 · Cited by 19 · see citing works
MicroRNAs, Stem Cells in Bipolar Disorder, and Lithium Therapeutic Approach
Coradduzza, D., Garroni, G., Congiargiu, A., Balzano, F., Cruciani, S., Sedda, S., Nivoli, A., & Maioli, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810489 · Cited by 17 · see citing works
Martinez, B., & Peplow, P. V. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.387966 · Cited by 16 · see citing works
The protective role of Neuregulin1-ErbB4 signaling in a chronic social defeat stress model
Wang, W., Qiao, Y., Qu, H., Zhu, L., Mu, L., Li, C., Fang, J., & Lian, H. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001464 · Cited by 13 · see citing works
Cattane, N., Courtin, C., Mombelli, E., Maj, C., Mora, C., Étain, B., Bellivier, F., Cynthia Marie-claire, A., & Cattaneo, A. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-04286-3 · Cited by 13 · see citing works
Ji, X., & Zhao, Z. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.01.002 · Cited by 12 · see citing works
Min, X., Liu, H., Dou, X., Chen, F.-X., Zhao, Q., Xiao-hong, Z., Shi, Y., Zhao, Q.-Y., Sun, S.-J., Wang, Z., et al. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.09.016 · Cited by 12 · see citing works
The Dysregulation of microRNAs and the Role of Stress in the Pathogenesis of Mental Disorders
Ivanova, E., Bozhilova, R., Kaneva, R. P., & Milanova, V. K. (2018) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666181130135253 · Cited by 11 · see citing works
Song, Z., & Wang, J. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.634933 · Cited by 9 · see citing works
Reduction of GAS5 and FOXD3-AS1 long non-coding RNAs in patients with bipolar disorder
Zamani, B., Mohseni, M. M., Gargari, B. N., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-41135-z · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Montel Hayes, R., Mason, C. E., & Miller, J. J. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1671122 · Cited by 5 · see citing works
- Authors
- Ni, L., Zhu, Y., Lv, L., Zhang, R., Xie, S., & Zhang, X.
- Affiliations
- Nanjing Brain Hospital (CN)
- Xuzhou Medical College (CN)
- Corresponding author
- Xie, Shiping
- Zhang, Xiangrong
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2025-08
- Volume
- 382
- Pages
- 453-461
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W4409663785
- Cited by
- 3
- References
- 53
- Citations by year
- 2026: 1 · 2025: 2
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Social Science Foundation of Jiangsu Province (BE2023668)
- Nanjing Municipal Health Bureau (YKK23134, ZKX21033)
- National Natural Science Foundation of China (82371510)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- miR-16-5p, microRNA biomarkers, bipolar II disorder, major depressive disorder, differential diagnosis, unmedicated patients, peripheral blood, hypomania, clinical course, miRNA differential expression
- MeSH terms
- Adult, Bipolar Disorder, Major Depressive Disorder, Depressive Disorder, Major, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Biomarkers, MicroRNAs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review