5. MiRNA and RNA as genetic candidates in ADHD.
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5. MiRNA and RNA with possible expression abnormalities in ADHD
- 5.1. MiR-let-7d
- 5.2. Rno-let-7b-5d
- 5.3. MiR-let-7b-5p
- 5.4. MiR-652-3p
- 5.5. MiR-942-5p
- 5.6. MiR-148b-3p
- 5.7. MiR-181a-5p
- 5.8. MiR-320a
- 5.9. MiR-18a-5p
- 5.10. MiR-22-3p
- 5.11. MiR24-3p
- 5.12. MiR-106b-5p
- 5.13. MiR107
- 5.14. MiR-155-5p
- 5.15. MiR-26b-5p
- 5.16. MiR-185-5p
- 5.17. MiR-191-5p
- 5.18. MiR-101-3p
- 5.19. MiR-130a-3p
- 5.20. MiR-138-5p
- 5.21. MiR-195-5p
- 5.22. MiR-106b-5p
- 5.23. MiR-138
- 5.24. MiR-138*
- 5.25. MiR-34c*
- 5.26. MiR-296
- 5.27. MiR-494
- 5.28. MiR-641
- 5.29. MiR-96
- 5.30. Pri-miR34b/c
- 5.31. HOTAIR, HOX TRANSCRIPT ANTISENSE RNA, NONCODING
- 5.32. MiRNA-4655-3p
- 5.33. MiRNA-7641
5. MiRNA and RNA with possible expression abnormalities in ADHD
miRNAs are microRNAs. They regulate the expression of genes at the posttranscriptional level. Read 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 section ⇒ Emergence.
miRNAs have been substantially implicated in the development of ADHD in children and adults.1
5.1. 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%. In a follow-up 1 year later, improvements in ADHD symptomatology correlated with normalized miR-let-7d levels.2
Meanwhile, one study found elevated galectin-3 blood plasma levels in ADHD-affected children.3
5.2. 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.
5.3. MiR-let-7b-5p
One study found aberrant (but not significant) expression of this miRNA in ADHD affected versus unaffected individuals.5
5.4. MiR-652-3p
One study found significant aberrant expression of this miRNA in ADHD affected versus unaffected individuals.5
5.5. MiR-942-5p
One study found significant aberrant expression of this miRNA in ADHD affected versus unaffected individuals.5
5.6. MiR-148b-3p
One study found significant aberrant expression of this miRNA in ADHD affected versus unaffected individuals.5
5.7. MiR-181a-5p
One study found aberrant (but not significant) expression of this miRNA in ADHD affected versus unaffected individuals.5
5.8. MiR-320a
One study found aberrant (but not significant) expression of this miRNA in ADHD affected versus unaffected individuals.5
5.9. MiR-18a-5p
The expression of this microRNA is reported to be altered in ADHD.6
5.10. MiR-22-3p
The expression of this microRNA is reported to be altered in ADHD.6
5.11. MiR24-3p
The expression of this microRNA is reported to be altered in ADHD.6
5.12. MiR-106b-5p
The expression of this microRNA is reported to be altered in ADHD.6
5.13. MiR107
The expression of this microRNA is reported to be altered in ADHD.6
5.14. MiR-155-5p
The expression of this microRNA is reported to be altered in ADHD.6
5.15. 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
5.16. 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 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
5.17. 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 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
5.18. MiR-101-3p
One report found significantly increased expression of this miRNA in ADHD.8
5.19. MiR-130a-3p
One report found significantly increased expression of this miRNA in ADHD.8
5.20. MiR-138-5p
One report found significantly increased expression of this miRNA in ADHD.8
5.21. MiR-195-5p
One report found significantly increased expression of this miRNA in ADHD.8
5.22. MiR-106b-5p
One report found significantly decreased expression of this miRNA in ADHD.8
5.23. 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
5.24. 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
5.25. 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
5.26. 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
5.27. 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
5.28. 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
5.29. MiR-96
miR-96 targets a SNP in the serotonin receptor HTR1B , which is associated with ADHD.10
5.30. 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
5.31. 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
5.32. 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
5.33. 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/
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. ↥
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 ↥ ↥ ↥ ↥ ↥ ↥
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 ↥
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. ↥
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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. ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
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. ↥ ↥ ↥
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. ↥ ↥ ↥ ↥ ↥
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. ↥
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. ↥
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. ↥
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. ↥
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 ↥ ↥