In-depth look at what causes ADHD including: deficiency in neurotransmitters, genetics, brain abnormalities, environmental agents plus food additives and sugar.
Although the exact causes of ADHD are unknown, it is most likely caused by an interaction of genetic, environmental, and nutritional factors, with a strong focus on the interaction of multiple genes (genetic loading) that together cause ADHD.
The Role of Neurotransmitters in Attention Deficit Disorder
There is some evidence that people with ADHD do not produce adequate quantities of certain neurotransmitters, among them dopamine, norepinephrine, and serotonin. Some experts theorize that such deficiencies lead to self-stimulatory behaviors that can increase brain levels of these chemicals (Comings DE et al 2000; Mitsis EM et al 2000; Sunohara GA et al 2000).
Epinephrine activation of receptors on the cranial vagus nerve increases the release of central norepinephrine and has been shown to enhance memory formation. Patients with ADHD have been shown to have a reduced urinary epinephrine level. Contrary findings are seen in patients with anxiety or PTSD. Given the high incidence of anxiety within ADHD patients as well as the increased risk of accident and injury, testing of epinephrine in ADHD patients should consider these other factors in order to have a better understanding of the role of epinephrine in ADHD.
ADHD is believed to be in part the result of a reduced or hypodopaminergic state. In conjunction with this assumption are the needs for stronger and less delayed behavioral reinforcement. Dopamine is involved in the reward cascade and the increased reinforcement threshold may be a manifestation of the hypodopaminergic state. Children with ADHD have displayed normal task performance under conditions of high incentive, but deficient performance under conditions of low incentive. Methylphenidate is believed to be beneficial in ADHD in part due to its ability to enhance dopamine signaling and therefore may enhance a deficient reward system in ADHD patients. Like many parameters that affect cognitive performance, dopamine levels also display an inverted U-shaped curve when plotted against factors like impulsivity.
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The development of the dopamine system prior to and during early adolescence is quite rapid, while the development of the serotonin system during this same time remains steady. A relative deficit in dopamine maturity would be concordant with an increased impulsivity and increased reward threshold seen in ADHD.
A delayed rate of brain development in ADHD is also supported by studies that find patients have increased level of delta and theta brain wave activity compared to controls. Delta and theta brain wave activity normally decreases until adulthood. As such, increased delta and theta wave brain activity can be an indicator of slowed brain maturity. Differences in the rate of serotonin and dopamine system development also may explain why significant numbers of children outgrow their ADHD symptoms.
Norepinephrine is an excitatory neurotransmitter that is important for attention and focus. Norepinephrine is synthesized from dopamine by means of the enzyme dopamine beta-hydroxylase, with oxygen, copper, and vitamin C as co-factors. Dopamine is synthesized in the cytoplasm, but norepinephrine is synthesized in the neurotransmitter storage vesicles.; Cells that use norepinephrine for formation of epinephrine use SAMe as a methyl group donor. Levels of epinephrine in the CNS are only about 10% of the levels of norepinephrine.
The noradrenergic system is most active when an individual is awake, which is important for focused attention. Elevated norepinephrine activity seems to be a contributor to anxiousness. Also, brain norepinephrine turnover is increased in conditions of stress. Interestingly, benzodiazepines, the primary anxiolytic drugs, decrease firing of norepinephrine neurons.
PEA (phenylethylamine) is an excitatory neurotransmitter that tends to be lower in patients with ADHD. Studies that tested urine levels of PEA in subjects with ADHD during treatment with stimulants (methylphenidate or dextroamphetamine), found that the levels of PEA were increased. Additionally, studies report that the efficacy of the treatment correlated positively with the degree to which urinary PEA increased.
Many of the effects of serotonin occur due to its ability to modify the actions of other neurotransmitters. Specifically, serotonin regulates dopamine release. This is evident in the observation that antagonists of either the 5-HT2a or the 5-HT2c serotonin receptor will stimulate dopamine outflow while agonists inhibit dopamine outflow. Similarly, dopamine has a regulatory effect on serotonin and neonatal damage to the dopamine system has been shown to cause large increases in serotonin.
Aspects of the interaction between serotonin and dopamine are believed to affect attention. Evidence of this interaction is present in the observation that reduced serotonin synthesis impairs the positive effects of methylphenidate on learning. Meaning some aspects of methylphenidate's therapeutic effects require serotonin. Serotonin levels are significantly affected by stress and coping abilities combined with other environmental factors and the person's genetic make-up to determine serotonin activity.
Brain Structural Differences in Attention Deficit Hyperactivity Disorder
There may also be some structural and functional abnormalities in the brain itself in children who have ADHD (Pliszka SR 2002; Mercugliano M 1999). Evidence suggests that there may be fewer connections between nerve cells. This would further impair neural communication already impeded by decreased neurotransmitter levels (Barkley R 1997). Evidence from functional studies in patients with ADHD demonstrates decreased blood flow to those areas of the brain in which "executive function," including impulse control, is based (Paule MG et al 2000). There may also be a deficit in the amount of myelin (insulating material) produced by brain cells in children with ADHD (Overmeyer S et al 2001).
- Created: 21 December 2008
- Last Updated: 10 July 2014