Let’s continue our exploration of the biology of ADHD by now turning to ADHD neurotransmitters (NT).
ADHD Neurotransmitter regulation is very complex
The general impression with ADHD is that the dopamine systems are not working right, especially when needed during concentration. Additionally, the neurotransmitter norepinephrine is also suspected by some to be involved as well. This is not a single problem in the biology of ADHD, but rather the end result of a number of things that can go awry at multiple levels of NT regulation:
- not enough substrate to make the NT
- abnormalities of the enzymes needed to make the NT
- lack of co-factors needed to support the enzymes (ie. iron, magnesium, zinc)
- problems with the transport systems involved (for both release and re-uptake)
- problems with the nerve endings cell membranes (ie. OM-3 deficiency)
- toxins that can affect any of these systems
It is important to say that ADHD symptoms do not correlate with blood levels of dopamine and norepinephrine, but rather reflect local dysregulation of these neurotransmitter (NT) systems in specific regions of the brain. The different constellation of symptoms we see probably reflect the fact that different regions are affected differently in different kids.
Different dopamine-using brain regions
For example, attention is usually more open in children like “Ryan” (read more about him here). These children are less able to filter out distracting stimuli. But other children become overly focused, and are instead unable to task switch easily without becoming very frustrated. And yet others seem to be “tuned inwardly,” seeming more dreamy and less participatory in the world outside. These differences likely involve systems such as the reticular activating system (norepiniphrine probably plays a more prominent role), the anterior cingulate cortex, and the prefrontal cortex.
Another example involves the levels of stimulation one seeks in order to feel comfortable. Classic ADHD children with hyperactivity seem to keep moving their bodies in order to produce the “right level of stimulation” for them. These children also seem to need more intense interactions and visuals to stay interested and focused. And some are much more prone to becoming addicted to all sorts of things: video games, smoking, drugs and alcohol, sexual encounters, and gambling to name a few of the big ones. These tendencies seem to mostly involve different parts of the basal ganglia system (striatum, substantia nigra) and the reward system (Nucleus accumbens (NA) and ventral tegmental area (VTA)).
And most people with ADHD struggle with executive functions like creating plans to reach a long-term goal, remaining focused and persistent towards that goal, monitoring progress and making the necessary adjustments to succeed. These processes are carried out mostly by the prefrontal cortex.
Abnormal levels of ADHD Neurotransmitters
There are a number of ways that normal neurotransmitter levels can become disrupted. Sometimes the substrate needed to make the neurotransmitter is present in sub-optimal quantities. For example, some people seem to benefit from taking supplements such as L-tyrosine. Sometimes the enzyme needed to convert the substrate into the NT is not working efficiently because of a relative lack of a necessary co-factor(s). Some of the necessary co-factors can be seen below. Iron, Zinc, and Magnesium have all been shown to benefit some patients with ADHD symptoms.
ADHD neurotransmitters and necessary co-factors
Additionally, there are sometimes differences in the efficiency of the transport systems or the enzymes that breakdown the neurotransmitters after they have been released into the synaptic space. For example, it has been shown that people with a faster COMT enzyme[degrades dopamine] in the prefrontal cortex correlates with functioning well in high stress/stimulating situations. But these same people have more trouble focusing and functioning at normal levels of stimulation.
Some of the most fascinating findings have to do with different versions of dopamine receptors and how they correlate with symptoms we call ADHD. We will talk more about some of the genetic contributions to these in the next post, and explore if there may even be an evolutionary advantage to this genetic variance.
If the neuronal cell membrane is not healthy, as in the example of a relative omega-3 fatty acid deficiency, it will not function efficiently and may cause ADHD symptoms. And lastly, toxins can disrupt these neurotransmitters systems at many different levels.
Take home: There are many different ways our biology can go awry when it comes to neurotransmitter systems. Some of these “aberrancies” result in challenges of attention, self-regulation, and executive function. In order to address the full range of possible disruptions to attention, self-regulation, and executive function, a holistic approach to ADHD is required.