Healthy Cognitive Function in Children

Childhood has both playful energies and a drive to learn and grow. It is a time when our brain plasticity rapidly expands, allowing for learning in behavioral, kinesthetic, and cognitive areas. That learning requires a healthy ability to focus. However, 9% of children in the US have trouble with this process.¹ It can be that an inability to attend and focus, or impulsivity and hyperactivity interrupt the learning process. This often results in impairment not only in academic but also in family and social settings.

Over the decades, studies have demonstrated a high degree of heritability for inattention, hyperactivity, or uncontrolled impulsivity in children.²  And, these conditions are increasing. Comparing data from the 2003 and 2007 National Survey of Children’s Health, the percentage of children aged 4-17 years with such impairment increased from 7.8% to 9.5% during 2003-2007, representing a 21.8% increase in just four years!³

What Could Be Contributing to Childhood Cognitive Impairment?

In David Rakel’s text: Integrative Medicine, 2nd ed., doctors McDonough-Means and Cohen report that cause is equally shared by genetic factors and environmental causes. Genetic factors include genetic vulnerability and a sensitive period of development.² Examples of environmental influencers include toxins, infectious agents, social and cultural factors, and general health status, including nutrition.² Here in this article, we examine the impact of genetic and environmental factors on neurotransmission in children with hyperactivity, impulsivity, or inattention.

The Contribution of Genetics

Genetic polymorphisms (SNPs) in both the dopamine (DA) and norepinephrine (NE) pathways have been widely investigated. In research on DA, for example, levels of hyperactive-impulsive symptoms (but not inattentive symptoms) were found to be related to the number of DAT1 (dopamine transporter) high-risk alleles in two genetic studies.^4,5 Two other studies found associations between an increase in inattentive symptoms and the DRD4 4-repeat allele.^5,6 Gold et al. suggest that by genotyping patients for a number of known associated dopaminergic SNPs, especially at an early age, misdiagnosis and/or over-diagnosis can be reduced.⁷

NE has also been a focus of this research. Norepinephrine transporter (NET) SNPs have been linked to focus issues. For example, Hohmann, et al. report associations for several variants of NET in a longitudinal German community sample.⁸ In a meta-analysis, Myer, et al. found multiple associated DNA variants, including SLC6A2 which encodes for NET, and ADRA2A, coding for the alpha-2-adrenergic receptor.⁹

Methylation Issues

We know that methylation can affect gene expression. Since both genetic variants and environmental factors appear to play a role in inattention, impulsivity, and hyperactivity, researchers have studied epigenetic changes, such as DNA methylation, as a possible link for their interplay.¹⁰ In one study the degree of methylation in the promoter region of DAT1 was found to correlate negatively with DAT availability, and DAT availability in the striatum correlated positively with inattention scores.¹¹ In plain English, the better the methylation, the lower the dopamine transporter activity and therefore, the better the attention scores. A similar study looking at the methylation of NET sites showed a negative correlation between NET gene methylation and severity of hyperactivity-impulsivity symptoms.¹² Preliminary data also imply a possible relationship between A1298C MTHFR polymorphisms and these lack-of-focus conditions.^13,14

Monitoring the ability to methylate by observing the norepinephrine-epinephrine (NE:EPI) ratio reported on the tests might help identify underlying methylation influences in individuals.

Neurotransmission and the Prefrontal Cortex

The prefrontal cortex (PFC) of the brain is implicated in impaired executive functions.¹⁵ Current research indicates that DA and NE are the primary neurotransmitters associated with the task of attending.² Additionally, behavioral disturbances are thought to result from an imbalance between these two systems in the PFC. In this instance, inhibitory dopamine activity is decreased while excitatory is increased.¹⁶ However, in other areas, such as the orbitofrontal cortex, NE levels were found to be in individuals with behavioral issues.¹⁷

We know that methylphenidate remediates these conditions, in part, by inhibiting NET and DAT.¹⁸ Based on the drug’s mechanism of action, it is proposed that inattention and hyperactivity are associated with excess transporter activity and therefore low catecholamine function. However, that hypothesis upon which areas of the brain are being studied. Measuring urinary NE and DA might be useful when analyzing individuals with focus issues.

Environmental Factor: Stress

Even in the non-stressed state, the HPA axis may be dysfunctional in children with focus issues, where the axis often appears to be under-reactive. The disturbance in the circadian rhythm of cortisol and the lack of its inhibition by dexamethasone have been documented in these populations.¹⁹ Many clinical data indicate that psychological stress evokes a weaker activation of the HPA axis in children with focus issues. In particular, the combined inattentive and hyperactive/impulsive type have a blunted cortisol response to stress and lower salivary cortisol than healthy individuals.^19-24 However, findings are inconsistent across studies, with some findings showing no association.²⁵

 Environmental Factor: Nutrition

Iron deficiency is a well-known factor contributing to focus issues. Studies in both rodents and human subjects show low iron and low ferritin.^26-28 Measuring ferritin in these children is recommended.

According to Dr. Rakel, the following biochemical risk factors are present in the population with focus issues:

• food and additive allergies/sensitivities
• heavy metal and other environmental toxicity
• low-protein, high-carbohydrate diets
• mineral imbalances
• essential fatty acid and phospholipid deficiencies
• amino acid deficiencies
• thyroid disorders
• B vitamin and phytonutrient deficiencies

“Nutritional management is the foundation in eliminating ‘obstacles to cure’ or healing and in some cases may be the primary therapeutic modality.”²

Environmental Factor: Screen Time

Numerous studies have examined the impact of screen time on infants through adolescence for everything from learning to social development to sleep among others. In school age children and older children, screen time did not seem to be a problem.²⁹ In fact, in older adults, internet use can increase brain activity.³⁰ However, in preschool age children, the results are very different. Researchers found that children who had increased screen time before the age of 3 performed poorly on developmental screens at age 3 and 5.³¹ Another study using longitudinal data found that increased screen time for children under the age of 5 had significantly more difficulty with attention.³² In general, researchers recommend no more than 1-2 hrs/day of screen time for children under the age of 5.^31,32

Supporting Healthy Cognitive Function in Children

The complexity of lack of focus and inattentiveness requires a carefully designed approach. Balancing neurotransmission, correcting nutritional deficiencies, addressing genetic influences, removing toxicities, and balancing the HPA axis can go far toward achieving a more normal life for the child with focus issues.

Neurotransmitter and HPA axis assessments are available through Sanesco healthcare providers. Find a provider near you or become a provider.

References

1. Attention-Deficit/Hyperactivity Disorder (ADHD). 2020 Nov. 16. Accessed on Sept. 16, 2021 at https://www.cdc.gov/ncbddd/adhd/data.html.
2. McDonough-Means SI and Cohen MW. Integrative Medicine. Rakel D. Elsevier. 2007:94-111.
3. Morbidity and Mortality Weekly Report. November 12, 2010 / 59(44);1439-1443.
4. Waldman ID, et al. Am J Hum Genet. 1998 Dec; 63(6): 1767–1776.
5. Gizer IR and Waldman ID. J Abnorm Psychol. 2012 Nov;121(4):1011-23.
6. Stevens EE, et al. J Abnorm Psychol. 2012 Nov;121(4):1011-23.
7. Gold MS, et al. Postgrad Med. 2014 Jan;126(1):153-177.
8. Hohmann S, et al. J Abnorm Psychol. 2012 Nov;121(4):1011-23.
9. Myer NM, et al. Mol Psychiatry. 2018 Sp;12(9):1929-1936.
10. Weig AL, et al. Neuropharmacology. 2021 Feb 15;184:108370.
11. Wiers CE, et al. Eur J Neurosci. 2018 Aug;48(3):1884-1895.
12. Sigurdardottir HL, et al. Mol Psychiatry. 2021; 26(3): 1009–1018.
13. Gokcen C, et al. Int J Med Sci. 2011; 8(7): 523–528.
14. Krull KR, et al. The Journal of Pediatrics 2008 Jan 1;152(1):101-105.
15. Littman EB. Toward an Understanding of the ADHD-Trauma Connection. 2009.
16. Russell V, et al. Behav Brain Res. 2000 Dec 20;117(1-2):69-74.
17. Somkuwar SS, et al. J Neurosci Methods. 2015 Aug 30;252:55-63.
18. Faraone SV, et al. Am J Psychiatry. 2001 Jul;158(7):1052-7.
19. Budziszewska B, et al. Przegl Lek. 2010;67(11):1200-4.
20. van West D, et al. European Child & Adolescent Psychiatry. 2009 Mar 18;18:543-553.
21. Moldonado EF, et al. Span J Psychol. 2009 Nov;12(2):707-14.
22. Chen Y, et al. Zhongguo Dang Dai Er Ke Za Zhi. 2009 Dec;11(12):992-5.
23. Kariyawasam SH, et al. Neuro Endocrinol Lett. 2002 Feb;23(1):45-8.
24. King JA, et al. Biol Psychiatry. 1998 Jul 1;44(1):72-4.
25. Kamradt J, et al. Attn Defic Hyperact Disord. 2018 Jun;10(2):99-111.
26. Li Y, et al. J Nutr. 2011 Dec; 141(12): 2133–2138.
27. Lahat E, et al. IMAJ Home Page. 2011 Sep;13(9):530-533.
28. Bianco LE, et al. Chronobiol Int. 2009 Apr;26(3):447-63.
29. Paulich KN, et al. PLoS One. 2021 Sep 8;16(9):e0256591.
30. Small GW, et al. Dialogues Clin Neurosci. 2020 Jun;22(2):179-187.
31. Madigan S, et al. JAMA Pediatr. 2019 Mar 1;173(3):244-250.
32. Tamana SK, et al. PLoS One. 2019; 14(4): e0213995.