Attention-deficit hyperactivity disorder: Encyclopedia II - Attention-deficit hyperactivity disorder - Possible causes

Attention-deficit hyperactivity disorder - Possible causes

ADHD is broadly defined and pervasive, and it is likely that the symptoms attributed to ADHD have a variety of different causes. The initial triggers could include genetic vulnerabilities, viral or bacterial infections, brain injury, or nutritional deficits. A 1990 study at the U.S. National Institute of Mental Health correlated ADHD with a series of metabolic abnormalities in the brain, providing further evidence that ADHD is a neurological disorder. While heredity is often indicated, some cases may arise from problems in prenatal development, birth complications, or later neurological damage may contribute to ADHD. The most compelling evidence at the moment suggests some role for maternal smoking and alcohol use to contribute to risk for the disorder (2.5 times increased risk for each). the total number of pregnancy complications may also increase risk for disorder. Prematurity has been repeatedly established as being associated with markedly elevated risk for disorder (30-50%), apparently due to the traumatic effects of birth on the premature brain resulting in minor bleeding and brain immaturity itself. The burgeoning field of epigenetics -- the study of what causes genes to express or not express -- is examining the questions concerning the interaction of these and other risk factors with genes that also contribute to risk for the disorder. There has been a surge in alternative approaches to causation ADHD, such as excess sugar, TV-viewing, video-game use, etc. but these have little research in support of them and have been vigorously disputed.

Attention-deficit hyperactivity disorder - Genetic vulnerabilities

It has been demonstrated that children who have at least one parent diagnosed with ADHD are more likely to be diagnosed with ADHD. Scientific evidence suggests most strongly that, in many cases, the disorder is genetically transmitted. If a parent has ADHD, their child is 8 times more likely to have ADHD, and a sibling is 5-7 times more likely to also have the same disorder. The concordance between identical twins if one has the disorder is 78-92%. Candidate genes have been identified as having some association with the disorder, as noted above. These genes imply that ADHD may result from an imbalance or deficiency in certain chemicals that regulate the efficiency with which the brain controls behavior. Current research is examining which genes may be involved. A team at the University of California suggest that genes contributing to (ADHD) overlap an area of chromosome 16p13, a marker that has repeatedly come up in genome-wide scans for autism genes. The two conditions appear related, with both (ADHD) and autism frequently involving inattentiveness and/or hyperactivity. Other studies have associated ADHD with the 10-repeat allele of the DAT1 gene and the 7-repeat allele of the DRD4 gene, both dopamine genes [1]. Several studies have now documented an association with the dopamine beta hydrozylase gene (DBH TaqI). Such research suggests that ADHD likely arises from a combination of these various risk genes rather than from a single gene. In the future it is likely that ADHD will be subtyped according to which risk genes individuals possess as these subtypes are likely to have different risks, life courses, and responses to treatment, particularly to medications.

There is no compelling evidence that social factors, alone, can create ADHD. What environmental factors have been identified to date fall in the realm of bio-hazards such as alcohol, tobacco smoke, lead poisoning, premature birth, excessively complicated pregnancy, etc.

Attention-deficit hyperactivity disorder - Neuro-chemical imbalance

There is increasing evidence that variants in the gene for the dopamine transporter are related to the development of ADHD (Roman et al., 2004, American Journal of Pharmacogenomics 4:83-92). This evidence is consonant with the theory of inefficacy of dopamine in people with ADD/ADHD; according to other recent studies, some people with ADHD usually have relatively high dopamine transporter levels, which clears dopamine from between neurons before the full effect is gained from dopamine. Stimulant medications used to treat ADHD are all capable of either inhibiting the action of dopamine transporter (as methylphenidate does) or promoting the release of dopamine itself (as the amphetamine-class medications do). Therefore, it is theorized that stimulant medication allows the brain to enhance the effect of dopamine by blocking dopamine transporters or increasing the release of dopamine. Currently this is the most widely accepted model of ADD/ADHD etiology in the scientific and medical community.

New studies consider the possibility that norepinephrine also plays a role. (see Krause, Dresel, Krause in Psycho 26/2000 p.199ff). Drugs that manipulate norepinephrine levels in certain brain regions, such as atomoxetine, have shown effectiveness for managing the disorder.

Attention-deficit hyperactivity disorder - Smoking during pregnancy

The finding of another possible cause stemmed from the observation that children of women who smoked during pregnancy are more likely to be diagnosed with ADHD (Kotimaa et al., 2003, J Am Acad Child Adol Psychiatry 42, 826-833). Given that nicotine is known to cause hypoxia (too little oxygen) in the uterus, and that hypoxia causes brain damage, smoking during pregnancy could be an important contributing factor leading to ADHD (or a phenocopy). It may even help explain in part the increase in ADHD diagnoses, as the number of women smokers has increased. However, there are not nearly enough women smoking during pregnancy to account for all the ADHD diagnoses, and the mothers of many of those diagnosed with ADHD did not smoke during or before pregnacy. It is also possible that cause and effect could be confounded in this study, since many mothers who smoke during pregnancy may be ADHD suffers themselves; therefore the cause may simply be the shared genetic material of mother and child, rather than the mother's smoking.

Brain development in the uterus and during the first year of life may be compromised by drug use during pregnancy or environmental toxins.

Attention-deficit hyperactivity disorder - Nutrition

It has also been suggested that ADHD may be the result of a poor diet and other external factors, rather than from any physiological source. Recent studies have begun to find metabolic differences in these children, indicating that it is not so much a poor diet, as it may be an inability to handle certain elements of the diet. For example, in 1990 the English chemist N.I. Ward showed that children with ADHD lose zinc when exposed to a food dye. Waring, McFadden, and others have shown that children with autism or ADHD are low in sulfation metabolism, in particular the enzyme Phenol Sulfotransferase-P.

Some children with ADHD seem to be addicted to milk. It has been proposed by Norwegian and British scientists that this is due to the casomorphins, peptides formed by incomplete digestion of the casein protein. While interesting, there is no compelling evidence that this in fact contributes to risk for the disorder.

It has, however, been established conclusively that some children are sensitive to dyes and other food additives, while a few may be sensitive to sugar, caffeine, etc. (Jacobson and Schardt, 1999, Diet, ADHD & Behavior, Center for Science in the Public Interest, Washington, DC). More studies supporting the connection between diet and behavior, including more than 30 double-blind studies, can be found at diet-studies.com.

Critics of dietary intervention for ADHD continue to claim that fewer than 5% of ADHD children appear to be diet sensitive. They say that the available evidence is insufficient to either prove or disprove a dietary connection.

Nutritional data has been well summarized in a review article (Burgess et al., 2000, Am J Clin Nutr 71:327-330). A few studies suggest that children with ADHD may have lower levels of key fatty acids but this remains to be replicated convincingly. In fact, one study found that the lower the levels, the worse the symptoms. The possibility that fatty acid deficiency is a trigger for ADHD may be plausible as nutrition scientists have recently demonstrated that the American diet is extremely deficient in omega-3 fatty acids. At the same time, ADHD diagnoses are rapidly increasing. More support for this idea comes from findings that breast-fed children have much lower levels of ADHD, and that until quite recently, infant formula contained NO omega-3 fatty acids. These remain purely correlational findings, however, that cannot be used to infer cause or the exact direction of the effects between these agents and ADHD symptoms. At present, experts do not accept the involvement of fatty acids as significant to the disorder or to its treatment.

A recent randomized double-blind experiment compared a fatty acid supplement with placebo in children with developmental coordination disorder (which exhibits a high degree of overlap with ADHD diagnoses). Fatty acid supplements improved spelling, reading, and behaviour after three months (Richardson and Montgomery, Pediatrics, 2005, 115:1360-1366). Numerous studies have shown an improvement in cognitive function, in mood, and in vision when omega 3 fatty acid supplements are given. While not directly showing a causal link between ADHD and fatty acids, increased levels of fatty acids has a beneficial effect on related behaviour.

Furthermore, creating a deficiency of omega-3 fatty acids in pregnant rats produces pups that are hyperactive and that have altered brain levels of dopamine in the same brain regions as seen in humans and other rat models of hyperactivity. More research, however, is clearly needed before dietary supplements, such as those involving fatty acids can be recommended for clinical use.

Attention-deficit hyperactivity disorder - Sleep apnea

There is also new evidence that brief pauses in breathing (apnea) during infancy may be a cause of ADHD. Dr. Glenda Keating of Emory University presented data at the Society for Neuroscience annual meeting in October 2004, showing that repetitive drops in blood oxygen levels in newborn rats similar to that caused by apnea in some human infants is followed by a long-lasting reduction in dopamine levels, associated with ADHD. Apnea occurs in up to 85% of prematurely born human infants. ^[2] Though intriguing, these findings with rats must be replicated in humans.

Attention-deficit hyperactivity disorder - Head injuries

It has been known for some decades that head injuries can cause a person to experience and display ADHD-like symptoms.

Brain scan technology has revealed differences in the size, symmetry, metabolism, and chemistry of the brain in those who have ADHD. However, it should be noted that there is yet no clear determination of the source of these differences. Some recent studies, such as that by Loo and colleagues at UCLA Medical School (Journal of the American Academy of Child and Adolescent Psychiatry, 2005) suggest that they are likely to be associated with the differences in genes discussed above. For instances, differences in the length of the DAT1 gene have been found to be linked to both differences in EEG patterns and to likelihood of responding to methylphenidate.

Adapted from the Wikipedia article "Possible causes", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki