Dopamine, norepinephrine and glutamate go too high in manic phases, dopamine and norepinephrine go to low in bipolar depression, serotonin can be too low in a depression phase or in the manic phase causing aggression and low impulse control. This is a bit of an oversimplification but it’s a useful practical model that I use in my practice and have applied to my own bipolar disorder to keep it under control.
Understanding bipolar neurotransmitters imbalances can help us to keep our condition under controlBipolar is a lot more than just out of balance neurotransmitters, there’s over-activation of the stress pathway called the HPA axis resulting in increased neuro-inflammation, there’s deficient levels of the brain's growth hormone-like protein BDNF and the combination of these two can result in loss of neuroplasticity and function key structures that regulate mood and the biological clock that runs our circadian rhythm and sleep cycles, there’s also evidence of mitochondrial dysfunction and excessive oxidative stress in the bipolar brain. I discuss how to combat each of these elsewhere. In this section however we’ll look at imbalances in bipolar neurotransmitters and how learning to take control of them gives us an effective and practical way to take control of our condition.
Dopamine and NorepinephrineAlterations in dopamine and norepinephrine have profound effects on the functioning of our brain and therefore our mind and behaviors, and there’s robust scientific evidence that the bipolar brain does not keep the levels of these neurotransmitters in balance in the same way that non-bipolar brains do. One of the most useful strategies I learned to live well with my own bipolar syndrome that I now teach to my patients is to learn to recognise when your levels of dopamine and norepinephrine are going out of balance and to control the level of these neurotransmitters yourself rather like a diabetic has to take control of their blood sugar and insulin levels because their body doesn’t do it naturally for them.
For more details on how to adjust your neurotransmitters see:
See How to Treat Bipolar Mania
and How to Treat Bipolar Depression
Dopamine the driver of hedonistic and addictive behavioursDopamine gives the brain energy, drive, excitement about life, quick switched-on thinking, curiosity and interest in pursuing new experiences, the pleasure and reward we experience in pursuing in exciting/thrill-seeking behaviors. Dopamine is sometimes called the hedonistic molecule, it’s powerful stuff imbalances in dopamine drives us towards everything that feels good from chocolate ice cream to cocaine, from a fun rollercoaster ride to good sex, from high stress business deals to gambling. I’ve talked extensively about the nature and characteristics of dopamine elsewhere (see dopamine deficient depression), the important point to understand with regard to bipolar is that imbalances in dopamine explain a lot of bipolar behaviour. It’s interesting to note that a person in a manic state behaves very similarly to a person high on cocaine and we know cocaine floods the brain with dopamine.
The embarrassing darker side of bipolar is the hedonistic behaviours that are so often part of the condition, excessive use of drugs, increased libido and hypersexual behaviours, gambling, excessive spending, are all common features that can wreak havoc in the lives of people with bipolar disorder; the scientific evidence is very strong that it’s imbalances in dopamine that drives these behaviours. Actually the conventional view increased dopamine drives these behaviours because there seen when we are in a manic state and dopamine levels are high and were also seen in Parkinson’s people given the drug L-dopa which is a direct precursor to dopamine however my personal experience and clinical observation suggests that low or falling or declining levels of dopamine are just as much a drive force behind bipolar hedonistic and addictive behaviours. The reason I believe this is there are times when I start thinking about the addictive and hedonistic behaviours that I do one a manic and when I say thinking I mean thinking a lot like they are intrusive thoughts I can’t stop thinking about them but as soon as I take remedies like tyrosine, DLPA and dopamine boosting herbs these thoughts stop, they are literally switched off; furthermore when I’m in that low dopamine depression with low energy and no pleasure in anything motivation my mind knows that drugs and sex would give me a lift and I’m interested in those things.
Part of the self-monitoring system I use myself and teach my patients is to make a list called my not-to-do list of things we do when we’re manic basically it’s a list of destructive things that we wish we would do less or not at all (see Self-Monitoring Bipolar Disorder)
- if you observe yourself thinking about or engaging in the things on your not to do list and other indicators such as your sleep and speed indicate you’re in or moving into a manic condition you would immediately attenuate or decrease your dopamine levels by stopping any dopamine boosting remedies you’re taking and using remedies that bring dopamine levels down including branched-chain amino acids, lithium orotate, et al.
- if you are in a normal balanced mood or depressed condition and start thinking about or engaging in the things on your not to do list immediately boost your dopamine levels with remedies such as tyrosine, DLPA, Rhodiola,
Norepinephrine the risk takerNorepinephrine is actually a derivative of dopamine, unfortunately I don’t have a way of either increasing or decreasing norepinephrine levels directly without simultaneously increasing or decreasing dopamine; hypothetically it may be useful to be able to target one and not the other but in practical terms I’ve never found not being able to do this it a hindrance because in the bipolar brain they both seem to go up or down together.
Higher levels of norepinephrine in key regions of the brain changes our perception of risk and loss, it makes us bigger risk takers, we don’t worry so much about the consequences or maybe even have the perception that a behaviour we’re about to do will work out okay even when it’s highly risky and we shouldn’t do it. The classic example of a person making bad risky choices is of course a person under the influence of alcohol, you may for example tell yourself it’s okay to drive your car when under the influence of alcohol even though you may know it’s not a sensible decision your feelings and perception tell you that it’ll be okay. When I’m in a manic phase I’ve taught myself to remember that my ability to make decisions in that condition is as bad as a drunk person and therefore I’m not allowed to make any big decisions or by anything other than the regular week’s groceries and I observed that as soon as I reduce the supply of tyrosine to my brain that reduces the supply of dopamine available to make norepinephrine (see the diagram) then I come to my senses and realise that that thing I was thinking of doing with a really bad idea.
When you have imbalanced dopamine driving you to pursue addictive and hedonistic pleasures coupled with imbalanced norepinephrine making you a risk taker and when this combination is coupled with elevated glutamate (discussed next) that stimulates and intensifies whatever is going on in the brain it can produce very destructive behaviours; I’ve met many people with bipolar disorder that have had their life destroyed by the risky behaviours bipolar disorder causes, they’ve lost their relationships, family, job, finances etc.
Glutamate the AcceleratorThe neurotransmitter glutamate is the brain’s primary stimulating neurotransmitter, it increases the level of activity in the brain and perpetuates signalling of thoughts going around and around in the mind. You could say whatever is going on in your brain glutamate is going to intensify it, in the anxious brain for example excess glutamate intensifies the anxiety in the bipolar brain however it speeds us up and intensifies anything else going on like imbalanced dopamine driving us to pursue addictive and hedonistic pleasures.
Elevated glutamate is the primary neurotransmitter speeding up the brain in bipolar mania when you get those racing frenzied thoughts, that’s too much glutamate.
In addition to speeding up the brain elevated glutamate levels are actually toxic to the brain and can cause nerve cells to die at an accelerated rate. In my practice my focus is always on dampening down excessive glutamate and continuously keeping a lid on it, I’ve never seen the need to increase glutamate levels during depression, boosting dopamine and sometimes serotonin is usually enough however if you wanted to boost glutamate levels you would use the amino acid L-glutamine; I used to prescribe L-glutamine for leaky gut syndrome but I no longer use it because elevated glutamate can be toxic to the brain, it causes glutamate excitotoxicity whereby excess glutamate causes nerve continuously fire and fire and fire until they become exhausted and die.
I don’t want to depress you but the glutamate excitotoxicity increases the chances of developing Alzheimer’s disease and untreated bipolar disorders associated with a greatly increased chance of developing Alzheimer’s disease; the good news is that there are medicines you can take that dampen down excessive glutamate and doing so appears to bring the risk of developing Alzheimer’s disease at least back down to the same levels of the general population.
To continuously combat the tendency for glutamate to go too high you can supplement lithium, I use a safe and side-effect free low dose lithium orotate rather than a high doses of lithium carbonate, zinc, NAC cysteine, glycine and taurine although the latter is more to build up GABA opposes elevated glutamate as opposed to reducing glutamate.
In a bout of mania very high but still safe doses of glycine can be quickly delivered to the brain by the sublingual (under the tongue) route. I wanted to experience first-hand how effective this technique was at combating a bout of mania but by the time I had heard of this technique I had already brought my condition largely under control and was rarely having manic hijackings so in order to conduct an experiment on myself I deliberately made myself manic by stopping all of my mood stabilising remedies and taking the maximum dose of all my antidepressant remedies including an enormous dose of bright light therapy first thing in the morning of the day the experiment, by midday I was quick thinking and creative and by three in the afternoon I was zipping around my flat, I had racing frenzied thinking and began to feel very anxious and agitated because everything was going to quickly; I put 18 g of glycine powder in a small dish and consume that half a teaspoon at a time holding each portion under my tongue for several minutes. Glycine is extremely sweet like fruit or icing sugar which made me feel quite nauseous but within 45 minutes it had tranquillized my brain, I didn’t feel great but it showed me glycine can be effective.
Serotonin the soother of depression and moderator of aggressionlow serotonin activity particularly in the frontal cortex of the brain is associated with low impulse control and aggression which are common behavioural problems for people with bipolar disorder in both the depressive and manic phases.
You have to be very cautious taking serotonin-based antidepressants (SSRIs, SNRI’s) when you have bipolar depression because they can induce mania and you wouldn’t take antidepressants when you are manic; however I have prescribed tryptophan* to many patients with bipolar depression and it did not cause mania, I have also given it to many patients during a phase of mania to help them sleep and control aggressive and impulsive behaviour.
*Don’t take tryptophan or 5 HTP on their own you must make also supplement B-Complex, magnesium and zinc to provide cofactors to direct tryptophan is towards serotonin rather than other toxic metabolites, you must also reduce overactive stress physiology.
[INSERT Chronic stress HPA AXIS 22-25% loss of serotonin receptor sites in hippocampus]
As you probably already know low serotonin can contribute to depression, a low-serotonin depression is more painful, sensitive and teary than the low energy, numb type depression caused by the dopamine; unfortunately you can have both low serotonin and low dopamine at the same time there is nothing fair in health and medicine!
Serotonin levels affect our sleep directly and because melatonin the sleep hormone is manufactured from serotonin, being depressed and waking too early especially in an anxious and depressed state I believe is an indicator of low serotonin.
Serotonin may not play a significant role in individual cases of bipolar disorder, the only reliable way to know whether or not boosting serotonin is useful for you is to try serotonin boosting remedies and see how they affect you.
[Insert personal anecdote]
Acetyl choline[cholinergic system is underactive during mania but cautioned supplementing coin bitartrate UNDER CONSTRUCTION/NOT FINISHED]
Believe it or not bipolar disorder responds well to treatment and as long as some form of treatment is continuously maintained it’s possible to live well with bipolar syndrome and keep it in more or less permanent remission