Attention-Deficit/Hyperactivity Disorder: A Comparative Analysis of Genetic and Psychosocial Origins in Recent Research

Öz

Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition that affects approximately 5–10% of children and 2.5% of adults worldwide. This comprehensive review examines the relative contributions of genetic and psychosocial factors to the etiology of ADHD through the analysis of twin studies, genome-wide association studies (GWAS), environmental research, and gene–environment interaction studies. Current evidence indicates that ADHD is highly heritable, with heritability estimates consistently ranging from 70% to 80% in twin studies. Recent GWAS have identified 27 genome-wide significant loci explaining approximately 22% of the phenotypic variance. However, environmental factors such as prenatal exposures, psychosocial adversities, and toxin exposure also significantly contribute to the development of the disorder and the severity of its symptoms. Emerging epigenetic research suggests that gene–environment interactions through DNA methylation and histone modifications may provide a mechanistic link between genetic predisposition and environmental triggers. This study concludes that ADHD represents a complex interplay between significant genetic susceptibility and modifiable environmental influences, supporting a multifactorial model rather than a purely genetic or environmental explanation.

Anahtar Kelimeler

• ADHD
• genetics
• environment
• heritability
• twin studies
• GWAS
• gene-environmental interaction
• epigenetics

Dikkat Eksikliği ve Hiperaktivite Bozukluğu: Genetik ve Psikososyal Kökenler Güncel Araştırmaların Karşılaştırmalı Analizi

Öz

Dikkat Eksikliği/Hiperaktivite Bozukluğu (DEHB), dünya çapında çocukların yaklaşık %5-10'unu ve yetişkinlerin %2,5'ini etkileyen yaygın bir nörogelişimsel durumdur. Bu kapsamlı derleme, ikiz çalışmaları, genom çapında ilişki çalışmaları (GWAS), çevresel araştırmalar ve gen-çevre etkileşimi çalışmalarının analizi yoluyla genetik ve psikososyal faktörlerin DEHB etiyolojisine göreceli katkılarını incelemektedir. Güncel kanıtlar, DEHB'nin oldukça kalıtımsal olduğunu ve ikiz çalışmalarında kalıtım tahminlerinin sürekli olarak %70-80 olduğunu göstermektedir. Son GWAS çalışmaları, fenotipik varyansın yaklaşık %22'sini açıklayan 27 genom çapında önemli lokus belirlemiştir. Bununla birlikte, doğum öncesi maruziyetler, psikososyal olumsuzluklar ve toksin maruziyeti gibi çevresel faktörler de bozukluk gelişimine ve semptom şiddetine önemli ölçüde katkıda bulunmaktadır. Yeni ortaya çıkan epigenetik araştırmalar, DNA metilasyonu ve histon modifikasyonları yoluyla gen-çevre etkileşimlerinin, genetik yatkınlık ile çevresel tetikleyiciler arasındaki mekanik bağlantıyı sağlayabileceğini öne sürmektedir. Bu çalışmamda, DEHB'nin önemli genetik yatkınlık ile değiştirilebilir çevresel etkiler arasında karmaşık bir etkileşimi temsil ettiği ve salt genetik veya çevresel bir açıklamadan ziyade çok faktörlü bir modeli desteklediği sonucuna ulaşılmıştır.

Anahtar Kelimeler

• DEHB
• genetik
• çevre
• kalıtım
• ikiz çalışmaları
• GWAS
• gen-çevre etkileşimi
• epigenetik

Destekleyen Kurum

İstanbul Aydın Üniversitesi

Etik Beyan

bu çalışma literatür taramasına dayalı olup herhangi bir deneysel uygulama içermediğinden etik kurul onayı gerektirmemektedir.

Kaynakça

1. Aarnoudse-Moens, C. S., Weisglas-Kuperus, N., van Goudoever, J. B., & Oosterlaan, J. (2009). Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics, 124(2), 717- 728.
2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Publishing.
3. Boomsma, D., Busjahn, A., & Peltonen, L. (2002). Classical twin studies and beyond. Nature Reviews Genetics, 3(11), 872-882.
4. Bouchard, M. F., Bellinger, D. C., Wright, R. O., & Weisskopf, M. G. (2010). Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics, 125(6), e1270-e1277.
5. Brennan, P. A., Hammen, C., Sylvers, P., Bor, W., Najman, J., Lind, P., ... & Williams, G. M. (2011). Interactions between the COMT Val108/158Met polymorphism and maternal prenatal smoking predict aggressive behavior outcomes. Biological Psychiatry, 69(8), 748-755.
6. Brikell, I., Kuja-Halkola, R., & Larsson, H. (2015). Heritability of attentiondeficit hyperactivity disorder in adults. American Journal of Medical Genetics Part B, 168(6), 406-413.
7. Burt, S. A. (2009). Rethinking environmental contributions to child and adolescent psychopathology: A meta-analysis of shared environmental influences. Psychological Bulletin, 135(4), 608-637.
8. Burt, S. A., Klump, K. L., Gorman-Smith, D., & Neiderhiser, J. M. (2016). Neighborhood disadvantage alters the origins of children's nonaggressive conduct problems. Clinical Psychological Science, 4(3), 511-526.

9. Burt, S. A., Pearson, A. L., Carroll, S., Klump, K. L., & Neiderhiser, J. M. (2016). Child antisocial behavior is more environmental in the context of child callous-unemotional traits. Child Development, 87(2), 556-571.
10. Choi, G., Polcher, A., Joas, E., & Landén, M. (2023). Prenatal air pollution exposure and DNA methylation alterations in cord blood associated with childhood ADHD. Environmental Research, 221, 115256.
11. Choi, Y. J., Cho, J., Hong, Y. C., Lee, D. W., Moon, S., Park, S. J., & Lim, Y. H. (2023). DNA methylation is associated with prenatal exposure to sulfur dioxide and childhood attention-deficit hyperactivity disorder symptoms. Scientific Reports, 13(1), 3501.
12. Creswell, J. W., & Creswell, J. D. (2017). Research design: Qualitative, quantitative, and mixed methods approaches (5th ed.). Sage Publications.
13. Deault, L. C. (2010). A systematic review of parenting in relation to the development of comorbidities and functional impairments in children with attention-deficit/hyperactivity disorder (ADHD). Child Psychiatry & Human Development, 41(2), 168-192.
14. Demontis, D., Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., & Neale, B. M. (2019). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics, 51(1), 63- 75.
15. Demontis, D., Walters, G. B., Athanasiadis, G., Walters, R., Therrien, K., Nielsen, T. T., & Børglum, A. D. (2023). Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Nature Genetics, 55(2), 198-208.
16. Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry, 24(4), 562-575.
17. Faraone, S. V., Asherson, P., Banaschewski, T., Biederman, J., Buitelaar, J. K., Ramos-Quiroga, J. A., ... & Franke, B. (2015). Attention-deficit/hyperactivity disorder. Nature Reviews Disease Primers, 1(1), 15020.
18. Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Sklar, P. (2005). Molecular genetics of attentiondeficit/ hyperactivity disorder. Biological Psychiatry, 57(11), 1313-1323.
19. Gizer, I. R., Ficks, C., & Waldman, I. D. (2009). Candidate gene studies of ADHD: A meta-analytic review. Human Genetics, 126(1), 51-90.
20. Goodlad, J. K., Marcus, D. K., & Fulton, J. J. (2013). Lead and attention-deficit/ hyperactivity disorder (ADHD) symptoms: A meta-analysis. Clinical Psychology Review, 33(3), 417-425.
21. Hinshaw, S. P., & Scheffler, R. M. (2014). The ADHD explosion: Myths, medication, money, and today's push for performance. Oxford University Press.
22. Huang, L., Wang, Y., Zhang, L., Zheng, Z., Zhu, T., Qu, Y., & Mu, D. (2018). Maternal smoking and attention-deficit/hyperactivity disorder in offspring: A meta-analysis. Pediatrics, 141(1), e20172465.
23. Kreppner, J. M., O'Connor, T. G., & Rutter, M. (2001). Can inattention/overactivity be an institutional deprivation syndrome? Journal of Abnormal Child Psychology, 29(6), 513-528.
24. Kreppner, J. M., O'Connor, T. G., Rutter, M., & English and Romanian Adoptees Study Team. (2007). Can inattention/overactivity be an institutional deprivation syndrome? Journal of Abnormal Child Psychology, 29(6), 513-528.
25. Larsson, H., Chang, Z., D'Onofrio, B. M., & Lichtenstein, P. (2014). The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychological Medicine, 44(10), 2223-2229.
26. Martin, J., Hamshere, M. L., Stergiakouli, E., O'Donovan, M. C., & Thapar, A. (2018). Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population. Biological Psychiatry, 76(8), 664-671.
27. Mills, J., Bonner, A., & Francis, K. (2006). The development of constructivist grounded theory. International Journal of Qualitative Methods, 5(1), 25- 35.
28. Neale, B. M., Medland, S. E., Ripke, S., Asherson, P., Franke, B., Lesch, K. P., ... & Nelson, S. (2010). Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 49(9), 884-897.
29. Nigg, J. T. (2006). What causes ADHD? Understanding what goes wrong and why. Guilford Press.
30. Nigg, J. T. (2012). Future directions in ADHD etiology research. Journal of Clinical Child & Adolescent Psychology, 41(4), 524-533.
31. Nigg, J. T. (2013). Attention-deficit/hyperactivity disorder and adverse health outcomes. Clinical Psychology Review, 33(2), 215-228.
32. Nigg, J. T., Nikolas, M., Knottnerus, G. M., Cavanagh, K., & Friderici, K. (2010). Confirmation and extension of association of blood lead with attentiondeficit/ hyperactivity disorder (ADHD) and ADHD symptom domains at population-typical exposure levels. Journal of Child Psychology and Psychiatry, 51(1), 58-65.
33. Nigg, J. T., Sibley, M. H., Thapar, A., & Karalunas, S. L. (2020). Development of ADHD: Etiology, heterogeneity, and early life course. Annual Review of Developmental Psychology, 2, 559-583.
34. Nigg, J., Nikolas, M., & Burt, S. A. (2010). Measured gene-by-environment interactions in relation to attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 49(9), 863-873.
35. Nikolas, M. A., & Burt, S. A. (2010). Genetic and environmental influences on ADHD symptom dimensions of inattention and hyperactivity: A metaanalysis. Journal of Abnormal Psychology, 119(1), 1-17.
36. Pingault, J. B., Viding, E., Galéra, C., Greven, C. U., Zheng, Y., Plomin, R., & Rijsdijk, F. (2015). Genetic and environmental influences on the developmental course of attention-deficit/hyperactivity disorder symptoms from childhood to adolescence. JAMA Psychiatry, 72(7), 651-658.
37. Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007). The worldwide prevalence of ADHD: A systematic review and metaregression analysis. American Journal of Psychiatry, 164(6), 942-948.
38. Rea-Sandin, G., Del Toro, J., & Wilson, S. (2024). Gene-environment interactions in ADHD: The roles of SES and chaos. Behavior Genetics, 54(1), 119-136.
39. Russell, A. E., Ford, T., Williams, R., & Russell, G. (2014). The association between socioeconomic disadvantage and attention deficit/hyperactivity disorder (ADHD): A systematic review. Child Psychiatry & Human Development, 47(3), 440-458.
40. Russell, G., Ford, T., Rosenberg, R., & Kelly, S. (2014). The association of attention deficit hyperactivity disorder with socioeconomic disadvantage: Alternative explanations and evidence. Journal of Child Psychology and Psychiatry, 55(5), 436-445.
41. Sagiv, S. K., Epstein, J. N., Bellinger, D. C., & Korrick, S. A. (2013). Pre- and postnatal risk factors for ADHD in a nonclinical pediatric population. Journal of Attention Disorders, 17(1), 47-57.
42. Sandman, C. A., Buss, C., Head, K., & Davis, E. P. (2015). Fetal exposure to maternal depressive symptoms is associated with cortical thickness in late childhood. Biological Psychiatry, 77(4), 324-334.
43. Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012). Genetic architectures of psychiatric disorders: The emerging picture and its implications. Nature Reviews Genetics, 13(8), 537-551.
44. Taylor, M. J., Lichtenstein, P., Larsson, H., Anckarsäter, H., Greven, C. U., & Ronald, A. (2016). Is there a female protective effect against attentiondeficit/ hyperactivity disorder? Evidence from two representative twin samples. Journal of the American Academy of Child & Adolescent Psychiatry, 55(6), 504-512.
45. Taylor, M. J., Martin, J., Lu, Y., Brikell, I., Lundström, S., Larsson, H., & Lichtenstein, P. (2019). Association of genetic risk factors for psychiatric disorders and traits of these disorders in a Swedish population twin sample. JAMA Psychiatry, 76(3), 280-289.
46. Taylor, M. J., Martin, J., Lu, Y., Brikell, I., Lundström, S., Larsson, H., & Lichtenstein, P. (2023). A twin study of genetic and environmental contributions to attention-deficit/hyperactivity disorder over time. Journal of Child Psychology and Psychiatry, 64(10), 1453-1463.
47. Thapar, A., Cooper, M., Eyre, O., & Langley, K. (2013). What have we learnt about the causes of ADHD? Journal of Child Psychology and Psychiatry, 54(1), 3-16.
48. Thapar, A., Fowler, T., Rice, F., Scourfield, J., van den Bree, M., Thomas, H. & Hay, D. (2003). Maternal smoking during pregnancy and attention deficit hyperactivity disorder symptoms in offspring. American Journal of Psychiatry, 160(11), 1985-1989.
49. Thapar, A., Martin, J., Mick, E., Arias Vásquez, A., Langley, K., Scherer, S. W., & Holmans, P. (2016). Psychiatric gene discoveries shape evidence on ADHD's biology. Molecular Psychiatry, 21(9), 1202-1207.
50. Thapar, A., & Rutter, M. (2019). Do natural experiments have an important future in the study of mental disorders? Psychological Medicine, 49(7), 1079- 1088.
51. Thapar, A., & Rutter, M. (2021). Do natural experiments have an important future in the study of mental disorders? Psychological Medicine, 51(7), 1079- 1088.
52. Thomas, R., Sanders, S., Doust, J., Beller, E., & Glasziou, P. (2015). Prevalence of attention-deficit/hyperactivity disorder: A systematic review and metaanalysis. Pediatrics, 135(4), e994-e1001.
53. Van den Bergh, B. R., Mulder, E. J., Mennes, M., & Glover, V. (2008). Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: Links and possible mechanisms. A review. Neuroscience & Biobehavioral Reviews, 32(3), 425-447.
54. Walton, E., Pingault, J. B., Cecil, C. A., Gaunt, T. R., Relton, C. L., Mill, J., & Barker, E. D. (2017). Epigenetic profiling of ADHD symptoms trajectories: A prospective, methylome-wide study. Molecular Psychiatry, 22(2), 250-256.
55. Williams, N. M., Zaharieva, I., Martin, A., Langley, K., Mantripragada, K., Fossdal, R., ... & Thapar, A. (2010). Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: A genome-wide analysis. The Lancet, 376(9750), 1401-1408.
56. Young, S., Bramham, J., Gray, K., & Rose, E. (2018). The experience of receiving a diagnosis and treatment of ADHD in adulthood: A qualitative study of clinically referred patients using interpretative phenomenological analysis. Journal of Attention Disorders, 22(11), 1031-1041.