ADHD Neurology

ADHD is a neurological condition that affects roughly 1 in 10 humans. In some areas of the world, this can be as high as 4 in 10. In Australia, the prevelance reported by the ABS is 1 in 20, mostly because getting a diagnosis is problematic. Here we are going to take a look at ADHD Neurology, to understand how the two dominant forms work. Neurology is very complex, so this is going to be necesarrily simiplified. Even so, to get a full picture around this will take some time.

Brain and confused man

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Our goal here is to help you to understand:

  1. The most common mechanism behind why people who feel anxious, for 24+ months, feel anxious
    • Mostly too little Noradrenaline, sometimes too much
  2. How Tier 1 ADHD stimulants work
    • Improve Dopamine and Noradrenaline
  3. Where Bipolar can often get misdiagnosed and poorly treated
  4. Why SSRIs are generally ineffective for ADHD and ASD
    • Unless you are compatible with Fluoxetine or Sertraline
    • Why SNRI and NRI medication (Tier 3 and 2) is often helpful
    • Why some people need Beta Blockers (effectively the opposite of NRI)
  5. Why people get clumsy at the end of their Tier 1 medication
    • Why you may experience general gross movement problems (Dyspraxia, Restless Leg Syndrom)

Understanding Neurotypical Neurology

We are first going to look at an ideal brain, aka both Neurotypical and un-traumatised.

The Prefrontal Cortex

Here we will cover the basics of how Dopamine and Noradrenaline work in an ideal brain.

The front of our brain, just behind our forehead, is our PreFrontal Cortex (PFC). The PFC is what makes humans able to do the amazing thinking stuff that we do. It is our cognition – Cognitive Function (aka knowing and solving), and our Executive Function (doing advanced thought related skills). It’s primary neurotransmitter to do what it does is Dopamine.

The Mysterious Executive Function – human, not apes

Everyone talks about executive function, but almost every research article on Executive Function defines EF differently. That tells us they don’t actually have any idea what they mean when they say EF, but they think everyone does. In science, when you don’t find a good and consistent definition of a thing, that means they don’t really understand it. It’s not a good sign. Which is hilarious how often I read people speaking lyrically about all things EF.

The Amygdala, ‘Safe’ or ‘not Safe’

In the middle of our brain is a section called the Amygdala. Its job is to note what we are sensing and do a pattern match for “safe”. If what we sense matches to “safe”, our Amygdala reports feeling “happy” or “content” and we then look to see if we have any opportunities available to us. If what we sense does not match “safe”, our Amygdala reports the feeling “fear” if the pattern matches ‘about to hurt’, “anger” if the pattern matches ‘wrong and needs to be fixed’ (sense of justice, there’s a right way that things should happen), or “disgust” if the pattern matches ‘sickening’ (off food, faeces, someone does a disgusting behaviour). The feelings of fear, anger and disgust tell our PFC what to look for that would trigger that feeling. Once we locate it, we then enact our rehearsed action for that problem, or we default to Freeze, Fawn, Flight and Fight generally in that order of action (that’s the biological default, but some of us have different reflexes).

Below our Amygdala are four glands that convert Levodopa (L-dopa) from the blood that has gone through your Blood Brain Barrier into Dopamine (because Dopamine doesn’t go through that barrier) with the help of Ferritin (an iron serum in our blood) with the help of Vitamin C, Vitamin B6 and the hormone Oestradiol. Two of these glands feed two pathways that go to the front and back of the PFC. One of these glands feeds a pathway that goes to your Cerebellum, which controls our gross motor movements, like standing, walking and balance – low Dopamine here causes movement disorders, ranging from clumsy, through dyspraxia, up to restless leg syndrome and finally to Parkinson’s disease (depending on cause and severity). The last gland mostly feeds Dopamine to the middle brain sections, which diffuse to the rest of the brain.

The Synaptic Gap

Each neuron has a tendril branch that goes to a destination neuron, called an Axon. Just before the Axon gets to the destination neuron, there is a small gap called a Synapse (Synaptic Gap), on the other side of the gap is another short tendril called a Dendrite (more like a spike) that leads to the receiving neuron. A neurotransmitter gets stored in a tiny chamber at the end of the Axon at the Synaptic Gap.

The source Neuron sends a signal down the Axon via a cascade of ionic forms of four elements: sodium, chlorine, calcium and potassium. As this gets to the Synaptic gap, the build up of charge squirts some neurotransmitter into the gap, which allows the built up charge to cross the tiny gap and trigger some receptors on the other side, on the dendrite, which goes straight into the receiving neuron. The remainder of the Neurotransmitter is then flushed – some of it can be recycled. Think of it as a switch that is normally off, and then it turns on briefly, then goes off again.

Neurotransmitters

What is a neurotransmitter? A Neruostransmitter is a chemical, often made from hormones, that fills the Synaptic Gap, allowing the signal to bridge the gap from a source Neuron to a destination Neuron.

We have a bunch of them:

  • Dopaminergic Family (Dopamine, Noradrenaline and Adrenaline)
  • Seratonergic Family (Serotonin and Melatonin)
  • Endorphins (endogenous morphines)
  • Oxytocin
  • Endocannabinoids (named after cannabis)
  • Neonicotinoids (named after nicotine)
  • and far more that aren’t currently considered to be strongly connected to how we think, feel and behaviour (aka Mental Health)

We cover these in more detail here.

The Dopaminergic Family

Dopamine that isn’t used as a neurotransmitter is converted into Noradrenaline, which can be used to run other functions. Noradrenaline that isn’t used as a neurotransmitter is converted into Adrenaline.

I’m not going to cover the other neurotransmitters here as that is beyond the scope of this article. We have covered that in our Neurotransmitter section.

ADHD Neurology

I have described how the ideal brain works so that we can compared how the ADHD brain struggles.

ADHD, The 2 major types, 2 subtypes

ADHDers have a problem getting enough Dopamine into the Synaptic Gap for the neurological circuit to be completed. There are two primary reasons for this. The first is that the glands that make the Dopamine aren’t making enough. The second is that the Dopamine is being used poorly, often being quick converted to Noradrenaline or flushed as waste.

This can cause a secondary domino problem.

If you don’t make enough Dopamine, you probably don’t make enough Noradrenaline. If your brain flushes too much Dopamine after using it, then unused Dopamine isn’t being converted to Noradrenaline. Regardless of which path, this person will feel Anxious and Depressed.

The other variant is that your Dopamine is being converted too quickly to Noradrenaline, robbing your PFC of needed Dopamine and driving your Noradrenaline too high. This leads a person to always be on the edge of their seat ready for something bad, can lead to paranoia and psychosis, and at some point, exhausted because there is nothing left – too little Dopamine and too little Noradrenaline to function.

Remember that the Amygdala runs mostly on Noradrenaline. When it has the right amount of Noradrenaline, it can tell you when you are safe, and it can tell you when you aren’t. When it has the wrong amount, your Amygdala can’t confirm you are safe, so it constantly tells you that you are ‘not safe’. That feels like constant anxiety for no good reason. If you have a history of interacting with awful humans, or are Autistic too, this usually represents as social phobia / social anxiety.

High Noradrenaline, how it feels

High Noradrenaline feels like anxiety, aggression and paranoia. Very high levels look like paranoid psychosis. You are making connections to things that you would normally dismiss, but they seem really legit, you feel super alert, and the world seems super real. For people with ovaries, if your Oestradiol goes too high, you’ll flood your Amygdala with Noradrenaline, you’ll get very grandiose, energetic and make very poor decisions, but think they are brilliant. This is one of the common forms of Bipolar Affective Disorder (BPAD), and Clonidine is your friend for this part of your menstrual cycle. Technically, this is actually PMDD, but the powers that be are a bit slow to catch on to this.

Low Noradrenaline, how it feels

If you had low Noradrenaline, it feels like anxiety first – your Amygdala can’t determine that you are safe, so like above for High Noradrenaline, it reports ‘not safe’. So far, very similar. As that Noradrenaline drops lower, Depression sets in. At lower levels, you can start catastrophising, feeling doom and starting to look for ‘ultimate solutions’ to escape this. That can look like suicidal ideation and self harm. At lower levels, you will either be stuck in bed, or trying to delete your life.

BPAD, BPD, PMDD and ADHD

BPAD (BiPolar Affective Disorder) is a cyclic mood disorder. Theoretically speaking, BPAD should affect “males” and “females” the same. However, 80% of people diagnosed with BPAD have ovaries. That suggests to me that BPAD is often misdiagnosed.

In my opinion, if Lithium medication works for you, then it is real BPAD.

If Sodium Valproate works for you, it might be BPAD, but could just as easily be ADHD.

If Beta Blockers (like Clonidine) work, it’s ADHD.

If you’re Antipsychotics are what you have been prescribed, and they kind of work, find a better psychiatrist – ideally a private ADHD psychiatrist, and talk to them about ADHD and PMDD. More on PMDD just below.

You’ll also want to get in contact with an endocrinologist to get your hormones sorted out. This can be due to Oestradiol going too high, or because your Thryoid is sutbly out, making everything a mess.

PMDD (PreMenstrual Dysphoric Disorder) is often mistaken for BPAD, psychosis, drug addiction, BPD (Borderline Personality Disorder), and a host of other things. Effectively, things get really, really bad just prior to and sometimes during your menstrual cycle (menses). In a fairly large study, over two thirds of people diagnosed with PMDD took ADHD medication. If you recall that ADHD prevelance is supposed to be around 10%, 66% seems like there is an important link. We cover PMDD quite extensively here.

The vast majority of people diagnosed with BPD are misdiagnosed. Most commonly the person was diagnosed with BPD by a psychiatrist or GP that had no qualifications in ADHD. If this is you, get yourself checked out for ADHD. If you have active ovaries, also get checked for PMDD.

Medication, Biological problems need biological solutions

Two ways to tackle this directly (Tier 1).

  1. Methylphenidate (Ritalin and Concerta) or
  2. Amphetamine (Dextroamphetamine or Lis-dexamphetamine).
Medications

Methylphenidate

The Dopamine not being used well, or too quickly processed, is tackled by Methylphenidate, aka Ritalin or Concerta (the slow release and slightly different pathway version). This slows down the conversion of Dopamine to Noradrenaline for most people, and makes the receptors more sensitive on the Dendrite end of the Synaptic Gap so you need less Dopamine release to get the trigger working. This keeps more Dopamine at that gap ready to be used, so the circuit can work faster and for longer. This is like doing some fancy trick to your car so that the same fuel gets you further.

Methylphenidate has a secondary effect where it does the same thing to Noradrenaline, but not quite as strongly as it does for Dopamine.

Amphetamines

The second method is Amphetamines. Amphetamines come in three major forms, two of which are available in Australia. Dextroamphetamine (dexies), Lis-dexamphetamine (Vyvanse) and Methamphetamine (Meth, not available in Australia for ADHD). Some countries outside of Australia have a dex meth combo called Adderall. Each of these do effectively the same thing, but through different paths, so the exact biological effect can vary a bit. For example, Vyvanse makes some people angry, while may not; or the other way around.

Amphetamines will do everything that Methylphenidate does, plus while the medication is active, it prompts your glands to make a bit more Dopamine than they normally would. Technically, there are some really funky things going on in your brain to achieve this, but understanding that is outside the scope of this write up.

Importantly, neither Methylphenidate nor Amphetamines provide Dopamine, Noradrenaline or Adrenaline, or any of the base ingredients to make these.

Stimulant Myth 1, Stimulants are addictive

Many people consider stimulants to be addictive. In some contexts, this is accurate. There are medical texts that stated that if a person doesn’t need stimulant medication and it is taken at a high dose for a long time, they can become acclimitised to them and reliant on their effects. In my experience, this is mostly false. What is really happening here is that this person is self medicating with the wrong medications. When I have assisted the “addict” to get diagosed and properly medicated (at 1/100th the dose or less), they no longer use the illicit high dose street drugs.

Most ADHDers are on some kind of stimulant medication to compensate for the Dopamine problem they have. Most ADHDers often can’t remember if they took their medication and wait for a few errors or a mood drop to confirm that they did not take their medication before taking their forgotten meds. Most ADHDers don’t double dip their medications, because they don’t need to and it feels weird.

Stimulant Myth 2, Isn’t everyone improved by taking stims?

No.

First of all, we know that medicating ADHD helps ADHDers to focus, concentrate and perform better. This performance difference can be detected with very low amounts of medication, eg amphetamine. When non ADHDers were tested with this very low dose, neither they nor the tests they took could tell the difference between the amphetamine medication and a placebo sugar pill.

The Base Ingredients for the Dopaminergic Family

We are what we eat…

To make a biological chemical, you need to have consumed the basic source ingredients to make that chemical out of. To make the Dopamine family we need:

  • Tyrosine amine
    • Sourced mostly from meat
    • Tyrosine can be supplemented – you can get it in a protein powder (beware added caffeine)
  • Vitamins B6
    • Sourced commonly from meat, but there are many plant sources
    • Vitamine B6 can be supplemented
  • Vitamin C
    • Warning: Concentrated Vitamin C can block your metabolism of many medications, including ADHD medications, so take at least 1 hour away from a meal
    • Vitamine C can be supplemented
  • Ferritin [Iron]
    • Easily sourced via meat
    • Vegans and vegetarians may struggle to absorb enough
    • Iron can be supplemented
  • Oestradiol (estradiol in USA)
    • Sourced from saturated fats, which provide LDL cholesterol
    • LDL cholesterol is what you turn into your primary sex hormones (all sexes), which make Oestradiol
    • Oestradiol regulates and assists you extract Tyrosine (at the top), converting it to a chemical that can pass the Blood Brain Barrier, and regulates how much Dopamine you make – the more Oestradiol, the more Dopamine.
    • Progesterone at high levels can counter the Oestradiol regulation, decreasing how much you can make
    • Hormones can be supplemented
    • More on this in our section on PMDD here

If you are low in any of these, the meds can’t work. Also note, concentrated Vitamin C taken at the same time as your amphetamine or methylphenidate medication will interfere with metabolising those medications, so if you need to add Vitamin C to your diet, take it at least 1 hour away from your meds!

Why SSRI’s Generally Fail for ADHD

GP’s will generally try to help your anxiety and depression with a class of medication called SSRI. That stands for Select Serotonin Reuptake Inhibitor. Recall the bit where I talked about how Methylphenidate slowed down the conversion of Dopamine to Noradrenaline and improved its efficiency? That is essentially what “reuptake inhibitor” does, but for Dopamine. An SSRI does this same thing, but slowing down the conversion of Serotonin to Melatonin (when the light you see is dim) or it just being discarded (when it is bright). No one really knows what the Select means anymore. This is a good medication to give to a generally healthy neurotypical person who is going through a bit of life struggles. In about 6 weeks, it can help boost the Serotonin a bit.

What is the primary function of Serotonin? Two things. One, it helps give you a bit of thinking space between a stimuli occurring (like a bang, or someone’s bad behaviour) and you carrying out an action. If you don’t have enough time to think, you do the default. If you have a moment, you can pick a good option (if it exists). This effectively calms you down just a bit. The other big thing it does is helps manage the part of your brain that helps manage your other brain process resources (Resource Manager), so if for some reason your were not making enough of something, it gets a bit of a boost to do so. Low Serotonin DOES NOT cause ADHD, so this is minimally effective.

As an aside: coincidentally, the kind of stress that discombobulates healthy neurotypicals, which GP’s are eager to script SSRI medication for, resolves itself in about 6 weeks 9 out of 10 times… so is it the medication that helped?

Anyway, there are a few SSRI medications that have some interesting side effects that are useful for ADHDers. Fluoxetine at 60 mg and higher dose per average adult, will act as a weak NRI and DRI (Noradrenaline Reuptake Inhibitor and Dopamine Reuptake Inhibitor), but are also frequently incompatible for other reasons. That is, when it works, its great. When it doesn’t, its awful. Sertraline has a secondary effect where it indirectly acts as a Dopamine agitate, effectively equivalent to increasing how much Dopamine you make (synthesise) in your brain, but through a different pathway than the ADHD medications do. That means you can take both if you find that running out of Dopamine in the evenings is a problem.

SNRI and NRI, raising Noradrenaline

There is a class of medications called SNRI, which stands for Serotonin Noradrenaline Reuptake Inhibitor. This can help you if you’ve kind of got enough Dopamine to manage, but your Amygdala is low on Noradrenaline. The best one of this class is Desvenlafaxine (Pristiq). It acts as an indirect weak DRI, which does help ADHDers a bit, often good to use in tandem if your Noradrenaline is still low after taking the ADHD Tier 1 medications.

Clonidine and Guanfacine, decreasing Noradrenaline

Some of my clients have naturally high Noradrenaline, or find that the Tier 1 ADHD medications (Methylphenidate and Amphetamine) boost their average Noradrenaline too high, but they really do need the extra Dopamine support of Tier 1 medications. Two major methods to manage this, Clonidine and Guanfacine. There are a few ways to take these, and that is beyond the scope of this atricle.

Autism and ADHD

Finally, there are a large number of Autistic people who experience Cognitive Impairment and Executive Function Impairment that would benefit from these medications, because they are ADHDers too, but didn’t get diagnosed properly.

There is a very large overlap between Autistic Peeps and ADHDers. Some overly conservative publications suggest 35% plus, while more accurate (in my opinion) estimates have a much higher rate of around 80% plus.

We have talked about this in more detail here.