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3. MiRNA and RNA as genetic candidates in ADHD.

3. MiRNA and RNA as genetic candidates in ADHD.

3. MiRNA and RNA with possible expression abnormalities in ADHD

miRNAs are microRNAs. They regulate the expression of genes at the posttranscriptional level. For more, see Building blocks of heredity and behavior: Genes, DNA, RNA, proteins and co. In the section Genetic and epigenetic causes of ADHD - Introduction in the section Emergence.

miRNAs have been substantially implicated in the development of ADHD in children and adults.1

3.1. MiR-let-7d

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

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

3.2. Rno-let-7b-5d

In SHR, a rat species representing a purely genetic ADHD-HI, the 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

The synthesis of dopamine in the brain occurs in two steps. First, the amino acid tyrosine is catalyzed by the enzyme tyrosine hydroxylase and converted to l-3,4-dihydroxyphenylalanine (l-DOPA). L-dopa is converted to dopamine by aromatic l-amino acid decarboxylase.

3.3. MiR-let-7b-5p

One study found aberrant (but not significant) expression of this miRNA in ADHD sufferers compared with nonaffected individuals.5

3.4. MiR-652-3p

One study found significant aberrant expression of this miRNA in ADHD affected versus unaffected individuals.5

3.5. MiR-942-5p

One study found significant aberrant expression of this miRNA in ADHD affected versus unaffected individuals.5

3.6. MiR-148b-3p

One study found significant aberrant expression of this miRNA in ADHD affected versus unaffected individuals.5

3.7. MiR-181a-5p

One study found aberrant (but not significant) expression of this miRNA in ADHD sufferers compared with nonaffected individuals.5

3.8. MiR-320a

One study found aberrant (but not significant) expression of this miRNA in ADHD sufferers compared with nonaffected individuals.5

3.9. MiR-18a-5p

The expression of this microRNA is reported to be altered in ADHD.6

3.10. MiR-22-3p

The expression of this microRNA is reported to be altered in ADHD.6

3.11. MiR24-3p

The expression of this microRNA is reported to be altered in ADHD.6

3.12. MiR-106b-5p

The expression of this microRNA is reported to be altered in ADHD.6

3.13. MiR107

The expression of this microRNA is reported to be altered in ADHD.6

3.14. MiR-155-5p

The expression of this microRNA is reported to be altered in ADHD.6

3.15. 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.76

3.16. 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 widely expressed 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.76

3.17. 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 widely expressed 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.76

3.18. MiR-101-3p

One report found significantly increased expression of this miRNA in ADHD.8

3.19. MiR-130a-3p

One report found significantly increased expression of this miRNA in ADHD.8

3.20. MiR-138-5p

One report found significantly increased expression of this miRNA in ADHD.8

3.21. MiR-195-5p

One report found significantly increased expression of this miRNA in ADHD.8

3.22. MiR-106b-5p

One report found significantly decreased expression of this miRNA in ADHD.8

3.23. MiR-138

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

3.24. MiR-138*

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

3.25. MiR-34c*

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

3.26. MiR-296

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

3.27. MiR-494

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

3.28. MiR-641

miR-641 targets SNAP-25. SNAP-25 is an essential component of the SNARE (soluble N-ethylmaleimide-sensitive factor-binding protein receptor) complex. The 3′-UTR SNPs of SNAP-25 modify the binding site of miR-641 and contribute to several psychiatric disorders, including ADHD.96

3.29. MiR-96

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

3.30. Pri-miR34b/c

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

  • MET
  • NOTCH2
  • HMGA2

which promotes the development of ADHD.11

3.31. HOTAIR, HOX TRANSCRIPT ANTISENSE RNA, NONCODING

OMIM: HOTAIR, HOX TRANSCRIPT ANTISENSE RNA, NONCODING

The rs1899663 polymorphism of HOTAIR RNA is a possible ADHD risk, according to a study 12

3.32. MiRNA-4655-3p

In children with ADHD treated with MPH (Concerta) and atomoxetine, SNAP-V score of attention deficit symptoms correlated negatively with relative expression of miRNA-4655-3p and miRNA-7641 in one study. The authors suggest that serum expression of miR-4655-3p and miR-7641 could be used as biomarkers for diagnosis and outcome assessment of ADHD-HI,13

3.33. MiRNA-7641

In children with ADHD treated with MPH (Concerta) and atomoxetine, SNAP-V score of attention deficit symptoms correlated negatively with relative expression of miRNA-4655-3p and miRNA-7641 in one study. The authors suggest that serum expression of miR-4655-3p and miR-7641 could be used as biomarkers for diagnosis and outcome assessment of ADHD-HI,13

Further information about 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. 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.

  7. 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.

  8. 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.

  9. 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.

  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. 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.

  12. 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.

  13. 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