Dopamine and ADD/ADHD

Though there are many models that explain the symptoms of ADD/ADHD, one model that has stood the test of time is the neurobiological model. One class of neurotransmitters that gets brought up time and time again is catecholamines. Catecholamines include epinephrine, norepinephrine and dopamine. For this article we will be focusing on the impact dopamine has on brain function for kids and adults with ADD/ADHD.

Dopamine gets a lot of focus when the topic of ADD/ADHD comes up. This is because the it is often involved in brain functions that children or adults with ADD/ADHD have a hard time with. This includes motor coordination, motivation and reward, cognition, learning, attention and mood. It is thought to be the “pleasure system” of our brains meaning it promotes feelings of enjoyment and reinforcement to motivate performance (1). Dopamine affects our award centers. When we are deficient it makes learning very difficult. That feeling of accomplishment when we learn something new simply isn’t there. Medications such as Ritalin and Concerta try to stop the re-uptake of dopamine making the affects of dopamine last longer. There are many reasons why someone can be deficient in dopamine. It is important to understand what a dopamine deficiency can look like, how dopamine is made, the affects it has on the brain and what can be causing the deficiency.

A person diagnosed with ADD/ADHD does not automatically have a dopamine deficiency. According to the CDC more than half of children with ADHD have another disorder (2).  Because of this, children with ADHD may benefit from treatments beyond those specifically for ADHD (2).

Some classic signs of a dopamine deficiency include:

  • Feelings of worthlessness
  • Feelings of hopelessness
  • Self-destructive thoughts
  • Inability to handle stress
  • Anger and aggression while under stress
  • Feelings of tiredness, even after many hours of sleep
  • A desire to isolate yourself from others
  • Unexplained lack of concern for family and friends
  • Inability to finish tasks
  • Feelings of anger for minor reasons

Dopamine is just one of many neurotransmitters. Many of these symptoms look like deficiencies of other neurotransmitters such as serotonin, acetylcholine and norepinephrine. For example, a deficiency in serotonin may cause feelings of sadness for no reason, which can easily be mistaken as feelings of hopelessness or worthless. A serotonin deficiency also makes handling stress very difficult. It is important to understand that based on symptoms alone it is very common to miss which neurotransmitter you or your child is deficient in. This may be why a medication for a friend worked really well to help with his ADHD, but when you or your child tried it the results were not the same.

All neurotransmitters have three major mechanisms that need to take place in order to perform their functions:

  1. Synthesis and release
  2. Receptor binding and sensitivity
  3. Termination of the signal

Synthesis of Dopamine

In the central nervous system, dopamine is made in the substantia nigra pars compacta in the midbrain, the ventral mesencephalon and the hypothalamus. The production of dopamine in the brain begins with tyrosine. However, tyrosine is not made in the brain. Therefore, the real first step in making dopamine begins with the consumption of phenylalanine, an essential amino acid that is found in our food. Phenylalanine is converted in the liver to tyrosine. The enzyme that does this requires folate, iron and oxygen. Tyrosine is carried across the blood brain barrier by a transporter called LNAA. It is then converted to DOPA by another enzyme called tyrosine hydroxylatse, which requires oxygen, iron and tetrahydrobiopterin, which is derived from folate (1). DOPA is converted to dopamine by an enzyme called AAAD, which requires P-5-P to function properly.

As you can see, the production of dopamine requires a lot of nutrients. Making or synthesizing dopamine may be hindered if your diet is lacking in specific nutrients. A diet low in phenylalanine will prevent the production of dopamine right from the start. Phenylalanine is found in eggs, meat (including fish) and seeds. If blood sugar issues exist, also referred to as dysglycemia, then LNAA cannot carry tyrosine across the blood brain barrier. If tyrosine cannot be taken across the blood brain barrier then the one of the initial steps for dopamine production is prevented. What can cause dysglycemia? A diet high in carbohydrates and skipping meals. Breakfasts such as cereal, bagels, granola, oatmeal or doughnuts set the stage for dysglycemia. One study confirmed that higher carbohydrate meals tend to shift mechanisms in your body to produce more serotonin than dopamine, which is not good if you are dopamine deficient.

A lack of oxygen due to poor circulation, hypotension, hypertension or an anemia (iron or B-vitamin related) will prevent phenylalanine from becoming tyrosine, tyrosine from becoming DOPA and DOPA from becoming dopamine. Even an iron insufficiency rather than a full-blown iron anemia (a CBC that comes back low in iron, but not anemic) can cause problems in the production of dopamine.

Anything that prevents B-vitamins from being used in the body, whether that is a genetic defect such as the MTHFR gene or a lack of B-vitamins in the diet, will also cause a problem in the production of dopamine. The MTHFR genetic defect can cause the inability to use B-vitamins, specifically the active form of folate. The MTHFR gene is important in a process called methylation and was recently found to be associated in those with ADHD. Since we need methylation for many things (including proper brain development), it is not a surprise that lower methylation profiles in mothers have been associated with ADHD symptoms in their children. B-vitamins such as B12, folate and P-5-P are imperative for dopamine production. You can get a lack of B vitamins with a lack of protein and vegetables. Poor gut flora will also cause impaired folate production. Also, liver pathways must be working well to convert phenylalanine into tyrosine.  As you can see there are many underlying metabolic reasons for a dopamine deficiency.

Dopamine Receptor Binding and Sensitivity

Just like a specific key fits and unlocks certain doors, dopamine has to bind to receptors for function to happen. These receptors are ‘sensitive’ to dopamine. Hormones can cause a desensitization of receptors. Low testosterone and progesterone will affect how sensitive dopamine is to its receptors. Birth control pills change the levels of progesterone in females and will change how sensitive her dopamine receptors are. It is important to determine if other medications are causing a ‘desensitization’ reaction to occur.

The Termination of the Dopamine Signal

In order to have healthy neuronal firing, each neuron needs to have the appropriate levels of neurotransmitters. Like Goldilocks and the Three Bears, neurons can become unhealthy when they have too much or too little of a neurotransmitter. The levels need to be just right. In order for that to occur we need to make the neurotransmitter, use it and then get rid of it. When the need for dopamine is over, dopamine is absorbed by the presynaptic nerve endings. The reuptake or absorption of dopamine allows for dopamine to be recycled and then used again later when needed.. Enzymes COMT(catechol-o-methyltransferse)  or MAO catabolize (break down) those that aren’t recycled. In order for COMT to function it needs magnesium and methyl donors such as B12 and B9 (1). The end production is homovanillic acid, which can be measured in the urine to determine how well a person is producing dopamine.  When dopamine cannot be catabolized we see the effects of too much dopamine. This can manifest as anxiety, chronic pain, worry, insomnia, paranoia, excessive movement, tics or schizophrenia/psychosis.

Medications under the category of “methylphenidate” are CNS stimulants that work on the termination part of the dopamine mechanism. Examples of methylphenidates include Ritalin and Concerta. These medications block the dopamine transporter, which is the main mechanism for removal of extracellular dopamine. This causes an increase in extracellular dopamine in the brain (3). Dopamine is stopped from being absorbed back in the pre-synaptic cytosol and keeps it active longer. By allowing dopamine to stay active longer it counteracts the affects of low dopamine. This is why if the problem truly is a dopamine deficiency the medication works well. However, the medication is a temporary fix as it does ware off. Looking at the underlying mechanisms for why there is a dopamine or other neurotransmitter deficiency can be a permanent fix.

Understanding how dopamine is made is important in grasping the fact that nutrition has a huge impact on neurotransmitters. Deficiencies in nutrients can cause deficiencies in dopamine. Underlying metabolic conditions such as an anemia, a CBC that shows low iron levels, genetic defects, poor gut health and insufficient liver pathways all affect the production of dopamine. By addressing these there will be an enhancement of all neurotransmitters and a relief of ADD/ADHD symptoms.

References:

  1. Kharrazian, Datis. Mastering brain chemistry. 2014; 293-301.
  2. http://www.cdc.gov/ncbddd/adhd/features/adhd-keyfindings-psychiatric-comorbidity-school-children.html
  3. Volkow Nora D, et al. Therapeutic doses of oral methylphenidate significantly increases extracellular dopamine in the human brain. The Journal of Neuroscience. 2001;21:1-5.
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Dr. Brianne Holmes

Comments

  1. Nina Vepsä Says: May 4, 2018 at 4:54 pm

    If the problems isnt dopamine deficiency, but low serotonin or noradrenaline, and methylphenidates are taken, what will happen then?

    • Dr. Scott Beyer Says: May 27, 2018 at 8:43 am

      Nina,
      Drugs that fall under the methylphenidate class are thought to block the re-uptake of both dopamine and norepinepherine. This means that they are more readily available in the synaptic cleft for neurons to use. Dopamine and Norepinepherine are powerful activators of cortical activity which is why it can help in some cases of ADD/ADHD. Not everyone responds the same to it, so its important to look at some of the causative factors too!

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