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5. MiRNA and RNA as genetic candidates for ADHD

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5. MiRNA and RNA as genetic candidates for ADHD

5. MiRNA and RNA with possible expression deviations in ADHD

miRNAs are microRNAs. They regulate the expression of genes at the post-transcriptional level. Find out more at Building blocks of heredity and behavior: Genes, DNA, RNA, proteins and co. In the section Genetic and epigenetic causes of ADHD - introduction in the chapter Origin.

miRNAs are substantially involved in the development of ADHD in children and adults.1

5.1. MiR-let-7d

A study found significantly increased levels of the microRNA let-7d in the blood of 35 children with ADHD. The increased blood levels of miR-let-7d correlated with a 16.7-fold increased risk of ADHD. Elevated miR-let-7d levels were associated with reduced galectin-3 expression in 66%. In a follow-up 1 year later, improvements in ADHD symptoms correlated with normalized miR-let-7d levels.2

However, one study found excessive levels of galectin-3 in the blood plasma of children with ADHD.3

5.2. Rno-let-7b-5d

In SHR, a rat species representing a purely genetically caused ADHD-HI, miRNA let-7d is reported to be overexpressed in the PFC and to decrease the expression of galectin-3, leading to downregulation of tyrosine hydroxylase, which is a precursor of dopamine synthesis.4

5.3. MiR-let-7b-5p

One study found a different (but not significant) expression of this miRNA in people with ADHD compared to those without.5

5.4. MiR-let-7g-5p

A review reports miR-let-7g-5p in total white blood cells as a potential biomarker for ADHD.6

5.5. MiR-18a-5p

The expression of this microRNA is said to be altered in ADHD.7

5.6. MiR-22-3p

The expression of this microRNA is said to be altered in ADHD.7

5.7. MiR-24-3p

The expression of this microRNA is said to be altered in ADHD.7

5.8. MiR-26b-5p

A genome-wide miRNA expression study found that this miRNA significantly contributed to ADHD by altering the myo-inositol signaling pathway. d-Myo-inositol (1,4,5)-trisphosphate is an intracellular second messenger widely distributed in the brain that controls the biological response of a large number of hormones and neurotransmitters to target cells by regulating calcium release from intracellular stores.87

5.9. MiR-30e-5p

A review reports miR–30e-5p in total white blood cells as a potential biomarker for ADHD.6

5.10. MiR-34c*

Significantly decreased expression was found for this miRNA in the ADHD-HI rat model of SRH, which was associated with promoter inhibitory activity of the glucocorticoid receptor Nr3c1.2

5.11. Pri-miR34b/c

SNP in the promoter of pri-miR34b/c are thought to alter the expression of various genes, including

  • MET
  • NOTCH2
  • HMGA2

which promotes the development of ADHD.9

5.12. MiR-96

miR-96 targets a SNP in the serotonin receptor HTR1B, which is associated with ADHD.10

5.13. MiR-101-3p

One report found significantly increased expression of this miRNA in ADHD.11 in blood serum.6

5.14. MiR-106b-5p

The expression of this microRNA is said to be altered in ADHD711 in blood serum.6

5.15. MiR-107

The expression of this microRNA is said to be altered in ADHD.7

5.16. MiR-126-5p

A review reports miR-126-5p in total white blood cells as a potential biomarker for ADHD.6

5.17. MiR-130a-3p

One report found significantly increased expression of this miRNA in ADHD.11 in blood serum.6

5.18. MiR-138

Significantly decreased expression was found for this miRNA in the ADHD-HI rat model of SRH, which was associated with promoter inhibitory activity of the glucocorticoid receptor Nr3c1.2

5.19. MiR-138*

Significantly decreased expression was found for this miRNA in the ADHD-HI rat model of SRH, which was associated with promoter inhibitory activity of the glucocorticoid receptor Nr3c1.2

5.20. MiR-138-5p

One report found a significantly increased expression of this miRNA in the blood serum of ADHD11.6

5.21. MiR-140-3p

A review reports miR-140-3p in total white blood cells as a potential biomarker for ADHD.6

5.22. MiR-142-5p

A review reports miR-142-5p in total white blood cells as a potential biomarker for ADHD.6

5.23. MiR-148b-3p

One study found a significant deviation in the expression of this miRNA in people with ADHD compared to those without the disorder.5

5.24. MiR-151a-3p

A review reports miR-151a-3p in total white blood cells as a potential biomarker for ADHD.6

5.25. MiR-151a-5p

A review reports miR-151a-5p in total white blood cells as a potential biomarker for ADHD.6

5.26. MiR-155-5p

The expression of this microRNA is said to be altered in ADHD.7

5.27. MiR-181a-5p

One study found a different (but not significant) expression of this miRNA in people with ADHD compared to those without.5

5.28. MiR-185-5p

A genome-wide miRNA expression study found that this miRNA significantly contributed to ADHD by altering the myo-inositol signaling pathway. d-Myo-inositol (1,4,5)-trisphosphate is an intracellular second messenger that is widely distributed in the brain and controls the biological response of a large number of hormones and neurotransmitters to target cells by regulating calcium release from intracellular stores.87

5.29. MiR-191-5p

A genome-wide miRNA expression study found that this miRNA significantly contributed to ADHD by altering the myo-inositol signaling pathway. d-Myo-inositol (1,4,5)-trisphosphate is an intracellular second messenger that is widely distributed in the brain and controls the biological response of a large number of hormones and neurotransmitters to target cells by regulating calcium release from intracellular stores.87

5.30. MiR-195-5p

One report found a significantly increased expression of this miRNA in the blood serum of ADHD11.6

5.31. MiR-223-3p

A review reports miR-223-3p in total white blood cells as a potential biomarker for ADHD.6

5.32. MiR-296

Significantly decreased expression was found for this miRNA in the ADHD-HI rat model of SRH, which was associated with promoter inhibitory activity of the glucocorticoid receptor Nr3c1.2

5.33. MiR-200b-3p

One study reports that the miRNA miR-200b-3p and taurine were able to reduce the ADHD symptoms of SHR.12

5.34. MiR-320a

One study found a different (but not significant) expression of the miRNA miR-320a in people with ADHD compared to those without.5

5.35. MiR-486-5p

A review reports miR-486-5p in total white blood cells as a potential biomarker for ADHD.6

5.36. MiR-494

Significantly decreased expression was found for this miRNA in the ADHD-HI rat model of SRH, which was associated with promoter inhibitory activity of the glucocorticoid receptor Nr3c1.2

5.37. MiR-641

miR-641 targets SNAP-25. SNAP-25 is an essential component of the SNARE complex (soluble N-ethylmaleimide-sensitive factor-binding protein receptors). The 3′-UTR SNPs of SNAP-25 modify the binding site of miR-641 and contribute to several psychiatric disorders, including ADHD.137

5.38. MiR-652-3p

One study found a significant deviation in the expression of this miRNA in people with ADHD compared to those without the disorder.5

5.39. MiR-942-5p

One study found a significant deviation in the expression of this miRNA in people with ADHD compared to those without the disorder.5

5.40. MiR-4281

A review reports miR-4281 in blood serum as a potential biomarker for ADHD.6

5.41. MiR-4466

A review reports miR-4466 in blood serum as a potential biomarker for ADHD.6

5.42. MiR-4516

A review reports miR-4516 in blood serum as a potential biomarker for ADHD.6

5.43. MiR-4655-3p

In children with ADHD treated with MPH (Concerta) and atomoxetine, the SNAP-V score of attention deficit symptoms negatively correlated with the relative expression of miRNA-4655-3p and miRNA-7641 in one study. The authors suggest that the expression of miR-4655-3p and miR-7641 in serum could be used as biomarkers for the diagnosis and outcome assessment of ADHD-HI,14

5.44. MiR-4763

A review reports miR-4763 in blood serum as a potential biomarker for ADHD.6

5.45. MiR-6090

A review reports miR-6090 in blood serum as a potential biomarker for ADHD.6

5.46. MiR-7641

In children with ADHD treated with MPH (Concerta) and atomoxetine, the SNAP-V score of attention deficit symptoms negatively correlated with the relative expression of miRNA-4655-3p and miRNA-7641 in one study. The authors suggest that the expression of miR-4655-3p and miR-7641 in serum could be used as biomarkers for the diagnosis and outcome assessment of ADHD-HI,14

5.47. HOTAIR, HOX TRANSCRIPT ANTISENSE RNA, NONCODING

OMIM: HOTAIR, HOX TRANSCRIPT ANTISENSE RNA, NONCODING

The rs1899663 polymorphism of the HOTAIR RNA is a possible ADHD risk, according to a study. 15

Further information on the affected genes can be found in the gene databases
http://omim.org/ and http://www.uniprot.org/


  1. Srivastav, Walitza, Grünblatt (2018): Emerging role of miRNA in attention deficit hyperactivity disorder: a systematic review. Atten Defic Hyperact Disord. 2018 Mar;10(1):49-63. doi: 10.1007/s12402-017-0232-y.

  2. Wu, Peng, Yu, Zhao, Li, Jin, Jiang, Chen, Deng, Sun, Wu (2015): Circulating MicroRNA Let-7d in Attention-Deficit/Hyperactivity Disorder. Neuromolecular Med. 2015 Jun;17(2):137-46. doi: 10.1007/s12017-015-8345-y. n = 70

  3. Isık, Kılıç, Demirdas, Aktepe, Aydogan Avsar (2020): Serum Galectin-3 Levels in Children with Attention-Deficit/Hyperactivity Disorder. Psychiatry Investig. 2020 Mar;17(3):256-261. doi: 10.30773/pi.2019.0247. PMID: 32151128; PMCID: PMC7113172. n = 70

  4. Wu, Zhao, Zhu, Peng, Jia, Wu, Zheng, Wu (2010): A novel function of microRNA let-7d in regulation of galectin-3 expression in attention deficit hyperactivity disorder rat brain. Brain Pathol. 2010 Nov;20(6):1042-54. doi: 10.1111/j.1750-3639.2010.00410.x.

  5. Nuzziello, Craig, Simone, Consiglio, Licciulli, Margari, Grillo, Liuni, Liguori (2019): Integrated Analysis of microRNA and mRNA Expression Profiles: An Attempt to Disentangle the Complex Interaction Network in Attention Deficit Hyperactivity Disorder. Brain Sci. 2019 Oct 22;9(10). pii: E288. doi: 10.3390/brainsci9100288.

  6. Martinez B, Peplow PV (2023): MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder. Neural Regen Res. 2024 Mar;19(3):557-562. doi: 10.4103/1673-5374.380880. PMID: 37721284. REVIEW

  7. Paul, Reyes, Garza, Sharma (2019): MicroRNAs and Child Neuropsychiatric Disorders: A Brief Review. Neurochem Res. 2019 Nov 26. doi: 10.1007/s11064-019-02917-y.

  8. Sanchez-Mora, Garcia-Martínez, Pagerols, Soler, Rovira, Calvo, Padilla, Richarte, Corrales, Franke, de la Cruz, Casas, Cormand, Ramos-Quiroga, Arias-Vásquez, Ribases (2019): SU2 – CORRELATION ANALYSIS OF miRNA AND mRNA EXPRESSION PROFILES IN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM ADHD PATIENTS AND CONTROLS, European Neuropsychopharmacology, Volume 29, Supplement 3, 2019, Page S887, ISSN 0924-977X, https://doi.org/10.1016/j.euroneuro.2017.08.191.

  9. Garcia-Martínez, Sánchez-Mora, Pagerols, Richarte, Corrales, Fadeuilhe, Cormand, Casas, Ramos-Quiroga, Ribasés (2016): Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder. Transl Psychiatry. 2016 Aug 30;6(8):e879. doi: 10.1038/tp.2016.151.

  10. Sánchez-Mora, Ramos-Quiroga, Garcia-Martínez, Fernàndez-Castillo, Bosch, Richarte, Palomar, Nogueira, Corrales, Daigre, Martínez-Luna, Grau-Lopez, Toma, Cormand, Roncero, Casas, Ribasés (2013): Evaluation of single nucleotide polymorphisms in the miR-183-96-182 cluster in adulthood attention-deficit and hyperactivity disorder (ADHD) and substance use disorders (SUDs). Eur Neuropsychopharmacol. 2013 Nov;23(11):1463-73. doi: 10.1016/j.euroneuro.2013.07.002.

  11. Zadehbagheri, Hosseini, Bagheri-Hosseinabadi, Rekabdarkolaee, Sadeghi (2019): Profiling of miRNAs in serum of children with attention-deficit hyperactivity disorder shows significant alterations. J Psychiatr Res. 2019 Feb;109:185-192. doi: 10.1016/j.jpsychires.2018.12.013.

  12. Chang TM, Lin HL, Tzang CC, Liang JA, Hsu TC, Tzang BS (2024): Unraveling the Role of miR-200b-3p in Attention-Deficit/Hyperactivity Disorder (ADHD) and Its Therapeutic Potential in Spontaneously Hypertensive Rats (SHR). Biomedicines. 2024 Jan 10;12(1):144. doi: 10.3390/biomedicines12010144. PMID: 38255250; PMCID: PMC10813109.

  13. Németh, Kovács-Nagy, Székely, Sasvári-Székely, Rónai (2013): Association of impulsivity and polymorphic microRNA-641 target sites in the SNAP-25 gene. PLoS One. 2013 Dec 31;8(12):e84207. doi: 10.1371/journal.pone.0084207. eCollection 2013.

  14. Zhang, Zhu, Wu (2020): [Association of microRNA expression before and after drug therapy with clinical symptoms in children with attention deficit hyperactivity disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2020 Feb;22(2):152-157. Chinese. PMID: 32051083. n = 80

  15. Sayad, Badrlou, Ghafouri-Fard, Taheri (2020): Association Analysis Between the rs1899663 Polymorphism of HOTAIR and Risk of Psychiatric Conditions in an Iranian Population. J Mol Neurosci. 2020 Feb 8:10.1007/s12031-020-01499-7. doi: 10.1007/s12031-020-01499-7. PMID: 32036581.