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Blog post #3: “Is the cause of ADHD more effected by genetic or environmental factors?”

I’ve always wondered whether or not ADHD was a hereditary mental disorder, and after researching deeply through many articles and peer reviewed journals, I’ve came to the conclusion that ADHD is impacted by the genetics of a person, and that current research in the field suggests that certain genes does put some people in higher risk of having ADHD than others (Burton et al., 2019) (Faraone & Larsson, 2018) (Green et al. 2014) (Grimm, Kranz, and Reif, 2020) (Nhs, 2021) (Paloyelis et al. 2010) (Pettersson et al. 2015). However, despite most research proving that ADHD is very much hereditary (70-80% inharitability), there is still struggle to pinpoint the exact DNA/gene responsible (Burton et al., 2019) (Faraone & Larsson, 2018) (Green et al. 2014) (Grimm, Kranz, and Reif, 2020) (Nhs, 2021) (Paloyelis et al. 2010) (Pettersson et al. 2015).

                  Through detailed analysis of the study of birth weight and their child ADHD symptoms (using the autism- tics, ADHD, and other Comorbidities inventory) of 15,000 pairs of twins, where every 1 kg in weight difference between the twins, there will be an average increase in ADHD symptoms by 1 symptom and a half (Pettersson et al. 2015). This proves that despite having very similar genes, ADHD symptoms can still vary from person to person, in this case, ADHD seems to be caused by the overall development of the person before birth, suggesting that the development of ADHD may be more heavily influenced by the parent’s diet before and during pregnancy, instead of genetic reasons (Pettersson et al. 2015).

                  The genes that makes certain individuals more likely to be diagnosed with ADHD is likely more complex, and would not be a single genetic fault (Nhs, 2021). Many researchers have been trying to identify the single genetic reason for ADHD to be hereditary, it is very likely that the genetic cause for ADHD is a series of genetic faults/mutations that when it is on its own, does not cause someone to have ADHD, but only when they are all combined together makes people more likely to be diagnosed with ADHD (Nhs, 2021). Therefore, further understanding of ADHD are to come with the discovery of its complex genetic causes, and discovery of such genetic faults/mutations would also help us understand ADHD better and potentially create a cure.

                  People who are believed to be more at risk of having ADHD are people who are born with low birth-weight, born prematurely, born with epilepsy, or to suffer severe head injury at some point of their life (Nhs, 2021). Coincidentally, every group above except suffering severe head injury can be hereditary, where someone who is born with low birth-weight have a 81% chance to have a low birth-weight baby themselves, someone born pre-maturely have a 30-40% chance to give birth to a baby prematurely, and someone with epilepsy have a 30-40 chance to give birth to a baby with epilepsy (Demerath et al. 2007) (UChicagoMedicine). While those groups of individuals may seem unrelated, it is logical to assume that the genes which caused low birth-weight, prematurely born, and epilepsy may also be responsible for ADHD, or to create the faulty genes/mutations causing ADHD.

                  Through the study of consenting Children and their parents’ “ADHD-ness” with the SWAN scale, it is found the SWAN scale is capable of identifying differences between people with ADHD, people without ADHD, and people with different genetic variations but with ADHD (Burton et al. 2019). This is significant because it proves the genetic differences between people without ADHD, the people with ADHD, and people with different types of ADHD (Burton et al. 2019). With a large participant base and of different ethnic, gender, and of different life experience, the SWAN scale is able to always successfully identify those with and without ADHD, further enforcing the belief of certain complex genes that are responsible for ADHD (Burton et al. 2019).

During the research, they also tried using the SWAN scale to identify differences in genetic for other neurotypical disorders (anxiety, OCD, etc), yet it only proved to be sensitive to the genetic differences in ADHD, proving the importance of genetic factors in ADHD (Burton et al. 2019). This proves that ADHD does have a clear and identifiable genetic difference from other neurotypical disorders, which are suggested to have developed through environmental factors (Burton et al. 2019).

                  With a recent study conducted on 568 Dutch twins, it demonstrated the relation between ADHD and people’s cognitive measures, with kids ranging from 5-7 years old testing for elementary level Math and English abilities, and those diagnosed with ADHD performing slightly below average (Polderman et al. 2010). With difference already forming at a young age, it would be logical to assumed that ADHD was caused by genetic faults/mutations, that led to underdevelopments in some parts of the brain, causing people with ADHD to have a harder time learning in school (Polderman et al. 2010).

                  A study with 85 ADHD patients discovered that majority of their (44 out of 85 people) genes can be pieced onto a network consisting of several neuronal cell membrane proteins, furthermore, majority of the proteins identified are directly stimulated by ADHD medicines, proving the validity of the common proteins found (Polderman et al. 2010). This is important and proves the genetic effects of ADHD because it is an important discovery of common genes shared between ADHD patients, proving genetic relativity on the development of ADHD (Polderman et al. 2010). With further research about the protein network, it is highly likely that we might find the specific complex genes that are responsible for ADHD (Polderman et al. 2010).

                  Through studying the academic abilities between identical twins (shares 100% of their genes) and fraternal twins (share on average 50% of their genes), researchers found some identical twins with genetically lower attentiveness than others, which strongly links to hyperactivity or impulsivity, prominent symptoms of ADHD (Greven et al. 2014).  Moreover, it is found that fraternal twins are less likely to both have genetically lower attentiveness than others, further proving the prominence of genetic factors in ADHD (Greven et al. 2014). With the study of twins, who are raised in similar environments, with similar genes, it proves the validity of genetic effects on being diagnosed with ADHD or have ADHD symptoms (Greven et al. 2014).

                  Through another twin study conducted in UK, it is proven that although some identical twins may differ in IQ, but 83% of them would both struggle with their attention span and attention to detail, if one of them were to have ADHD (Paloyelis et al. 2010). This emphasizes the genetic presence of ADHD, proven through the same genes, different development regarding brain capability, yet they would both suffer with similar level of ADHD (Paloyelis et al. 2010).

                  Some identical twin may be smarter than the other twin, yet the smarter twin would struggle with the same inattentiveness when trying to achieve academic success, dispite some twins having better vocabulary or more advanced English ability, 55%-74% of them would score the same anyway, for they both struggle to extract useful information from the texts (Paloyelis et al. 2010). While ADHD is commonly associated with the hyperactivity and impulsivity of the individual, the study had shown that it is 2.5 times more likely for the identical twins to both have the same level of inattentiveness when compared to the genetic correlation of hyperactivity and impulsivity(Paloyelis et al. 2010).

                  A study of near 900 ADHD subjects and over 1100 of their siblings that are under the age of 17, above age of 5, their siblings have a nonuple chance of also having ADHD than the siblings of non-ADHD subjects (Faraone & Larsson, 2018). Although not conducted on twins with very identical genes, this still proves that ADHD is very heavily influenced by the genetic traits, where a sibling would have already have a greater chance of having ADHD, with the genes that they share (Faraone & Larsson, 2018).

                  Some studies may show a lower hereditary estimates of ADHD in children, for self-reported studies would associate with a lower hereditary estimate due to personal bias (average 30-40% hereditary estimates), whereas parent/teacher ratings of a child’s ADHD symptoms would often suggest an average 70-80% hereditary estimate (Faraone & Larsson, 2018). This is likely caused by personal bias from the child, not wanting to be diagnosed with a neurotypical disorder, while the parents and teachers knowing the child better, and wanting them to have an easier life if they found out about their ADHD diagnose sooner. However, it is also likely that both sides are biased, and the actual accurate hereditary estimate would end up in the middle, around 50%.

                  Most of the studies from before 2010 uses self-reported ADHD symptoms, while those conducted after 2010 would use subjects who are clinically diagnosed with ADHD, therefore, it is more likely that the studies after 2010 would be more accurate with the data, where it suggests a near 70-80% hereditary estimates on average (Faraone & Larsson, 2018). However, the rise of social media should also be taken into account, where more people are aware of ADHD, and are more likely to publicly appear as someone with ADHD.

                  Children with ADHD are more likely to have behavioral problems than other child, more likely to be antisocial, defiant, and even substance abuse problems, which often have little to no relation to one’s genes but their environment around them; however, some may argue that the behavioral problems are part of ADHD, and is therefore hereditary (Faraone & Larsson, 2018). The hereditariness of ADHD can be different depending on the definition of ADHD and what one considers a symptom of ADHD.

                  Neurological disorders can be all related to each other, with relatives of people with autism spectrum disorders being at a 50% more risk of having ADHD than others (Faraone & Larsson, 2018). Where a Swedish study discovered the strong genetic association, and the specific genetic factors that are known to cause both ADHD and ASD (Faraone & Larsson, 2018). With genetic correlation to other neurotypical disorders, it is increasingly likely that ADHD and other neurotypical disorders will be found to be caused by certain genetic faults/mutations (Faraone & Larsson, 2018).

                  Moreover, ADHD can also overlap with other internalizing disorders, overlapping with depression, and anxiety through shared genetic factors (Faraone & Larsson, 2018). The hereditariness of ADHD is not determined through the study of only ADHD, and true understanding of the genetic impact of ADHD can only be understood with the study of ones internal disorders, along with other neurotypical disorders, and only then we will be able to understand genes’ effect on ADHD better (Faraone & Larsson, 2018).

                  The genes causing ADHD is likely not something significant or something large enough to have effect on its own, instead it is very likely that ADHD’s hereditariness is caused by the combination of small families of genes, and when the small families are all gather together, one would have ADHD (Faraone & Larsson, 2018). This explains why no one have been able to find solid evidence of any gene causing ADHD yet, for the genes responsible for it would be small, complex group of genes.

                  The hereditary estimate of ADHD is like other neurotypical disorders, at 77-88%, with ASD at 80%, Bi-polar disorder at 75%, and Schizophrenia at 80% (Grimm, Kranz, and Reif, 2020). It is therefore reasonable for ADHD to be near the same hereditary estimate as other disorders within the same category, where the increase in hereditary estimate was a result of proper diagnosis, which is only reasonable to deduct that 77-88% hereditary chance is within reasonable range (Grimm, Kranz, and Reif, 2020).

                  With studies utilizing the Genome-Wide Association Studies (GWAS) growing in technical equipment advancement, and a bigger and more properly diagnosed subject base, a study have found the gene CHD13, which shows hyperactivity, learning deficits, and hyperlocomotion when tested on mices (Grimm, Kranz, and Reif, 2020). Moreover, it is then found to also be associated with many other neurotypical disorders (ASD, bi-polar, schizophrenia, depression), CHD13 could be the start of more understanding of neurotypical disorders (Grimm, Kranz, and Reif, 2020).

                  There are many types of ADHD, with 31.1% of the diagnosed ADHD patients only having the inattentive trait, 7.4% only having the hyperactive trait, and 14.8% having both inattentive and hyperactive traits, therefore, the genetic causes to ADHD may not be limited to one or one set of genes, but instead many combinations of complex little gene families that combine together to make ADHD symptoms (Grimm, Kranz, and Reif, 2020). With current research, the behavioral traits of ADHD is likely to be caused by the loss of function of the FMR1 gene, which is also found to cause tumors (Grimm, Kranz, and Reif, 2020).

For the next round of research, I plan to research about environmental factors that a person grows up in, and its effect on ADHD, it will help me understand how environmental factors can effect a person’s chance/likelihood, or if it impacts a person’s chance to get diagnosed with ADHD at all, and to help me form the conclusion of whether genetic factors or environmental factors are more influential to ADHD.

References:

Burton, C. L., Wright, L., Shan, J., Xiao, B., Dupuis, A., Goodale, T., Shaheen, S.-M., Corfield, E. C., Arnold, P. D., Schachar, R. J., & Crosbie, J. (2019). SWAN scale for ADHD trait-based genetic research: A validity and polygenic risk study. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 60(9), 988–997. https://doi.org/10.1111/jcpp.13032

Demerath, E. W., Choh, A. C., Czerwinski, S. A., Lee, M., Sun, S. S., Chumlea, W. C., Duren, D., Sherwood, R. J., Blangero, J., Towne, B., & Siervogel, R. M. (2007). Genetic and environmental influences on infant weight and weight change: The Fels Longitudinal Study. American Journal of Human Biology: The Official Journal of the Human Biology Council, 19(5), 692–702. https://doi.org/10.1002/ajhb.20660

Faraone, S. V., & Larsson, H. (2018). Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry, 24(4), 562–575. https://doi.org/10.1038/s41380-018-0070-0  

Greven, C. U., Kovas, Y., Willcutt, E. G., Petrill, S. A., & Plomin, R. (2014). Evidence for shared genetic risk between ADHD symptoms and reduced mathematics ability: A twin study. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 55(1), 39–48. https://doi.org/10.1111/jcpp.12090

Grimm, O., Kranz, T. M., & Reif, A. (2020). Genetics of ADHD: What should the clinician know? Current Psychiatry Reports, 22(4), 18. https://doi.org/10.1007/s11920-020-1141-x  

Nhs. (2021, December 24). Causes. Nhs.Uk. https://www.nhs.uk/conditions/attention-deficit-hyperactivity-disorder-adhd/causes/

Paloyelis, Y., Rijsdijk, F., Wood, A. C., Asherson, P., & Kuntsi, J. (2010). The genetic association between ADHD symptoms and reading difficulties: The role of inattentiveness and IQ. Journal of Abnormal Child Psychology, 38(8), 1083–1095. https://doi.org/10.1007/s10802-010-9429-7

Pettersson, E., Sjölander, A., Almqvist, C., Anckarsäter, H., D’Onofrio, B. M., Lichtenstein, P., & Larsson, H. (2015). Birth weight as an independent predictor of ADHD symptoms: A within-twin pair analysis. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 56(4), 453–459. https://doi.org/10.1111/jcpp.12299  

Polderman, T. J. C., Huizink, A. C., Boomsma, D. I., Verhulst, F. C., & Bartels, M. (2010). Genetic associations between ADHD symptoms and cognitive measures. European Child & Adolescent Psychiatry, 19, S47. https://doi-org.bc.idm.oclc.org/10.1007/s00787-010-0117-5

UChicagoMedicine. (n.d.). Causes of epilepsy. UChicago Medicine. Retrieved October 22, 2024, from https://www.uchicagomedicine.org/conditions-services/neurology-neurosurgery/epilepsy-seizures/causes

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