Dergiler / Black Sea Journal of Engineering and Science / 2026 / Cilt: 9 Sayı: 3

Possible Effect of Dysregulations in Dopamine Receptor Expression on Specific Learning Disorder: DRD1 and DRD2 Gene Expressions

Nil Özbilüm Şahin(Sivas Cumhuriyet Üniversitesi)0000-0002-2889-3600
Seher Derin(SİVAS CUMHURİYET ÜNİVERSİTESİ, FEN FAKÜLTESİ)0009-0002-2187-5837
Cansu Mercan Işık(CUMHURİYET ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR.)0000-0001-9437-3024
Burcu Bayyurt(CUMHURİYET ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR.)0000-0002-5618-457X
Sayfa
1321–1328
Yayın Tarihi
2026-05-15
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

In conclusion, these two genes, known to play a role in epigenetic processes, are considered potential therapeutic targets in SLD; however, further studies are needed to confirm this relationship.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Specific Learning Disorder (SLD) refers to impairments in a number of simple functions, including listening, speaking, basic reading, comprehension, arithmetic, mathematical reasoning, and written expression.
📊
Temel Bulgular & Veri:In recent years, biomolecules with significant structural and functional gene expression have played a crucial role in neurodevelopmental disorders.
💡
Sonuç & Katkı:In conclusion, these two genes, known to play a role in epigenetic processes, are considered potential therapeutic targets in SLD; however, further studies are needed to confirm this relationship.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:DRD1 · DRD2 · Gene expression

Özet

Specific Learning Disorder (SLD) refers to impairments in a number of simple functions, including listening, speaking, basic reading, comprehension, arithmetic, mathematical reasoning, and written expression. In recent years, biomolecules with significant structural and functional gene expression have played a crucial role in neurodevelopmental disorders. The dopamine receptor 1 (DRD1) gene encodes the DRD1 receptor. The dopamine receptor 2 gene encodes the DRD2 receptor. DRDs are highly expressed in the prefrontal cortex, which is responsible for movement, reward, reinforcement, memory, and learning. The aim of this study is to investigate the contribution of these biomolecules to the pathophysiology of the disease by examining the expression levels of the DRD1 and DRD2 genes, which belong to the dopamine gene family and play a significant role in sensory and motor skills, in individuals with SLD. This study involved blood samples from 38 children and adolescents aged 6-16 years diagnosed with SLD and a control group of 35 children and adolescents without any psychiatric disorders. RNA was isolated from these samples, and gene expression levels were analyzed using qPCR. The data were analyzed using the online analysis program Qiagen Gene Globe Data Analysis Center, and p-values and fold changes were determined. Comparison of the target genes with the reference gene (ACTB) revealed that while the DRD1 gene showed a 7.15-fold increase in the patient group, this result was not statistically significant (P=0.288). In contrast, the DRD2 gene exhibited a statistically significant 7.27-fold upregulation in individuals with SLD (P=0.001). In conclusion, these two genes, known to play a role in epigenetic processes, are considered potential therapeutic targets in SLD; however, further studies are needed to confirm this relationship.

Abstract

Specific Learning Disorder (SLD) refers to impairments in a number of simple functions, including listening, speaking, basic reading, comprehension, arithmetic, mathematical reasoning, and written expression. In recent years, biomolecules with significant structural and functional gene expression have played a crucial role in neurodevelopmental disorders. The dopamine receptor 1 (DRD1) gene encodes the DRD1 receptor. The dopamine receptor 2 gene encodes the DRD2 receptor. DRDs are highly expressed in the prefrontal cortex, which is responsible for movement, reward, reinforcement, memory, and learning. The aim of this study is to investigate the contribution of these biomolecules to the pathophysiology of the disease by examining the expression levels of the DRD1 and DRD2 genes, which belong to the dopamine gene family and play a significant role in sensory and motor skills, in individuals with SLD. This study involved blood samples from 38 children and adolescents aged 6-16 years diagnosed with SLD and a control group of 35 children and adolescents without any psychiatric disorders. RNA was isolated from these samples, and gene expression levels were analyzed using qPCR. The data were analyzed using the online analysis program Qiagen Gene Globe Data Analysis Center, and p-values and fold changes were determined. Comparison of the target genes with the reference gene (ACTB) revealed that while the DRD1 gene showed a 7.15-fold increase in the patient group, this result was not statistically significant (P=0.288). In contrast, the DRD2 gene exhibited a statistically significant 7.27-fold upregulation in individuals with SLD (P=0.001). In conclusion, these two genes, known to play a role in epigenetic processes, are considered potential therapeutic targets in SLD; however, further studies are needed to confirm this relationship.

🔖

Bu Makaleye Atıf Yap

Şahin, N. Ö., Derin, S., Işık, C. M., Bayyurt, B. (2026). Possible Effect of Dysregulations in Dopamine Receptor Expression on Specific Learning Disorder: DRD1 and DRD2 Gene Expressions. Black Sea Journal of Engineering and Science, Cilt: 9 Sayı: 3, 1321–1328. https://doi.org/10.34248/bsengineering.1896616

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (34)

  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5. bs.). American Psychiatric Publishing.
  2. Andreska, T., Lüningschrör, P., Wolf, D., McFleder, R. L., Ayon-Olivas, M., Rattka, M., Drechsler, C., Perschin, V., Blum, R., Aufmkolk, S., Granado, N., Moratalla, R., Sauer, M., Monoranu, C., Volkmann, J., Ip, C. W., Stigloher, C., & Sendtner, M. (2023). DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons. Cell Reports, 42(6), Article 112575. https://doi.org/10.1016/j.celrep.2023.112575
  3. Arnsten, A. F. T. (2011). Catecholamine influences on dorsolateral prefrontal cortical networks. Biological Psychiatry, 69(12), e89–e99. https://doi.org/10.1016/j.biopsych.2011.01.027
  4. Atasever, F., Şahin, N. Ö., & Işık, C. M. (2025). Altered expression of MeCP2 and PTEN genes in the molecular basis of specific learning disorder. Journal of Molecular Neuroscience, 75(2), Article 74. https://doi.org/10.1007/s12031-025-02370-3
  5. Bayyurt, B., Şahin, N. Ö., & Işık, C. M. (2024). Investigation of association between expression of DYX1C1, KIAA0319, and ROBO1 genes and specific learning disorder in children and adolescents. Journal of Molecular Neuroscience, 74(4), Article 109. https://doi.org/10.1007/s12031-024-02288-2
  6. Beaulieu, J.-M., & Gainetdinov, R. R. (2011). The physiology, signaling, and pharmacology of dopamine receptors. Pharmacological Reviews, 63(1), 182–217. https://doi.org/10.1124/pr.110.002642
  7. Chieffo, D. P. R., Arcangeli, V., Moriconi, F., Marfoli, A., Lino, F., Vannuccini, S., Marconi, E., Turrini, I., Brogna, C., Veredice, C., Antonietti, A., Sani, G., & Mercuri, E. M. (2023). Specific learning disorders (SLD) and behavior impairment: Comorbidity or specific profile? Children, 10(8), Article 1356. https://doi.org/10.3390/children10081356
  8. Cools, R., & D’Esposito, M. (2011). Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biological Psychiatry, 69(12), e113–e125. https://doi.org/10.1016/j.biopsych.2011.03.028
  9. Cui, Y., Prabhu, V., Nguyen, T. B., Yadav, B. K., & Chung, Y.-C. (2015). The mRNA expression status of dopamine receptor D2, dopamine receptor D3 and DARPP-32 in T lymphocytes of patients with early psychosis. International Journal of Molecular Sciences, 16(11), 26677–26686. https://doi.org/10.3390/ijms161125983
  10. Durstewitz, D., & Seamans, J. K. (2008a). The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia. Biological Psychiatry, 64(9), 739–749. https://doi.org/10.1016/j.biopsych.2008.05.015
  11. Durstewitz, D., & Seamans, J. K. (2008b). The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia. Biological Psychiatry, 64(9), 739–749. https://doi.org/10.1016/j.biopsych.2008.05.015
  12. Goldman-Rakic, P. S., Castner, S. A., Svensson, T. H., Siever, L. J., & Williams, G. V. (2004). Targeting the dopamine D1 receptor in schizophrenia: Insights for cognitive dysfunction. Psychopharmacology, 174(1), 3–16. https://doi.org/10.1007/s00213-004-1793-y
  13. Grigorenko, E. L., Compton, D. L., Fuchs, L. S., Wagner, R. K., Willcutt, E. G., & Fletcher, J. M. (2020). Understanding, educating, and supporting children with specific learning disabilities: 50 years of science and practice. The American Psychologist, 75(1), 37–51. https://doi.org/10.1037/amp0000452
  14. Grizzle, R. (2011). Wechsler Intelligence Scale for Children, Fourth Edition. In S. Goldstein & J. A. Naglieri (Eds.), Encyclopedia of child behavior and development (pp. 1553–1555). Springer. https://doi.org/10.1007/978-0-387-79061-9_3066
  15. Isik, C. M., Bayyurt, E. B. T., & Sahin, N. O. (2025). The MNK-SYNGAP1 axis in specific learning disorder: Gene expression pattern and new perspectives. European Journal of Pediatrics, 184(4), Article 260. https://doi.org/10.1007/s00431-025-06089-6
  16. Jasinska, A. J., Service, S., Choi, O., DeYoung, J., Grujic, O., Kong, S., Jorgensen, M. J., Bailey, J., Breidenthal, S., Fairbanks, L. A., Woods, R. P., Jentsch, J. D., & Freimer, N. B. (2009). Identification of brain transcriptional variation reproduced in peripheral blood: An approach for mapping brain expression traits. Human Molecular Genetics, 18(22), 4415–4427. https://doi.org/10.1093/hmg/ddp397
  17. Kaalund, S. S., Newburn, E. N., Ye, T., Tao, R., Li, C., Deep-Soboslay, A., Herman, M. M., Hyde, T. M., Weinberger, D. R., Lipska, B. K., & Kleinman, J. E. (2014). Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia and affective disorders, and associations with SNPs in postmortem brain. Molecular Psychiatry, 19(12), 1258–1266. https://doi.org/10.1038/mp.2013.165
  18. Kos, M. Z., Puppala, S., Cruz, D., Neary, J. L., Kumar, A., Dalan, E., Li, C., Nathanielsz, P., & Carless, M. A. (2022). Blood-based miRNA biomarkers as correlates of brain-based miRNA expression. Frontiers in Molecular Neuroscience, 15, Article 817290. https://doi.org/10.3389/fnmol.2022.817290
  19. Lawford, B. R., Young, R., Noble, E. P., Kann, B., & Ritchie, T. (2006). The D2 dopamine receptor (DRD2) gene is associated with co-morbid depression, anxiety and social dysfunction in untreated veterans with post-traumatic stress disorder. European Psychiatry, 21(3), 180–185. https://doi.org/10.1016/j.eurpsy.2005.01.006
  20. Lisman, J., Grace, A. A., & Duzel, E. (2011). A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP. Trends in Neurosciences, 34(10), 536–547. https://doi.org/10.1016/j.tins.2011.07.006
  21. Liu, L., Luo, Y., Zhang, G., Jin, C., Zhou, Z., Cheng, Z., & Yuan, G. (2016). The mRNA expression of DRD2, PI3KCB, and AKT1 in the blood of acute schizophrenia patients. Psychiatry Research, 243, 397–402. https://doi.org/10.1016/j.psychres.2016.07.010
  22. Liu, L., Luo, Y., Zhang, G., Jin, C., Zhou, Z., Cheng, Z., & Yuan, G. (2017). Correlation of DRD2 mRNA expression levels with deficit syndrome severity in chronic schizophrenia patients receiving clozapine treatment. Oncotarget, 8(49), 86515–86526. https://doi.org/10.18632/oncotarget.21230
  23. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
  24. Mascheretti, S., De Luca, A., Trezzi, V., Peruzzo, D., Nordio, A., Marino, C., & Arrigoni, F. (2017). Neurogenetics of developmental dyslexia: From genes to behavior through brain neuroimaging and cognitive and sensorial mechanisms. Translational Psychiatry, 7(1), e987. https://doi.org/10.1038/tp.2016.240
  25. Missale, C., Nash, S. R., Robinson, S. W., Jaber, M., & Caron, M. G. (1998). Dopamine receptors: From structure to function. Physiological Reviews, 78(1), 189–225. https://doi.org/10.1152/physrev.1998.78.1.189
  26. Özbilüm Şahin, N., Mercan Işık, C., & Bayyurt, B. (2025). Epigenetic signature of GOMAFU, MALAT1, NEAT1 lncRNAs in children with specific learning disorders: Expression differences. Journal of Psychiatric Research, 191, 482–490. https://doi.org/10.1016/j.jpsychires.2025.09.082
  27. Pedersen, R., Johansson, J., Nordin, K., Rieckmann, A., Wåhlin, A., Nyberg, L., Bäckman, L., & Salami, A. (2024). Dopamine D1-receptor organization contributes to functional brain architecture. The Journal of Neuroscience, 44(11), e0621232024. https://doi.org/10.1523/JNEUROSCI.0621-23.2024
  28. Pergola, G., Di Carlo, P., D’Ambrosio, E., Gelao, B., Fazio, L., Papalino, M., Monda, A., Scozia, G., Pietrangelo, B., Attrotto, M., Apud, J. A., Chen, Q., Mattay, V. S., Rampino, A., Caforio, G., Weinberger, D. R., Blasi, G., & Bertolino, A. (2017). DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia. Translational Psychiatry, 7(1), e1006. https://doi.org/10.1038/tp.2016.253
  29. Porteus, S. D. (1965). Porteus maze tests: Fifty years’ application. Pacific Books.
  30. Purves-Tyson, T. D., Owens, S. J., Rothmond, D. A., Halliday, G. M., Double, K. L., Stevens, J., McCrossin, T., & Shannon Weickert, C. (2017). Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain. Translational Psychiatry, 7(1), e1003. https://doi.org/10.1038/tp.2016.257
  31. Schultz, W. (2016). Dopamine reward prediction-error signalling: A two-component response. Nature Reviews Neuroscience, 17(3), 183–195. https://doi.org/10.1038/nrn.2015.26
  32. Shaywitz, S. E., & Shaywitz, B. A. (2005). Dyslexia (specific reading disability). Biological Psychiatry, 57(11), 1301–1309. https://doi.org/10.1016/j.biopsych.2005.01.043
  33. Wysokiński, A., Kozłowska, E., Szczepocka, E., Łucka, A., Agier, J., Brzezińska-Błaszczyk, E., & Sobierajska, K. (2021). Expression of dopamine D1−4 and serotonin 5-HT1A-3A receptors in blood mononuclear cells in schizophrenia. Frontiers in Psychiatry, 12, Article 645081. https://doi.org/10.3389/fpsyt.2021.645081
  34. Zhang, X., Han, Y., Liu, X., Chen, J., Yuan, Z., & Wang, Y. (2023). Assessment of genetic variants in D2 dopamine receptor (DRD2) gene as risk factors for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD): A systematic review and meta-analysis. Journal of Affective Disorders, 328, 312–323. https://doi.org/10.1016/j.jad.2023.02.001