Fluctuations in mood are normal in humans and essential to a good life. But what causes low mood and what can we do to help us feel better? Prof Grant Schofield, Chief Science Officer at PreKure, has released a white paper on the biology of mental wellbeing, to help explain the processes in the brain that drive how we feel. Read on for a deep dive into this fascinating science.


The serotonin hypothesis

For the past few decades, the main theory for depression and anxiety has been the serotonin hypothesis. At a very basic level, the neurotransmitter serotonin is thought to be low in people with depression. The theory is that prescribing drugs like SSRIs (Selective Serotonin Reuptake Inhibitors) could increase serotonin levels and have a positive effect on mood. 

The trouble is that meta-analyses of the clinical trials show a very small effect, especially when compared to placebo. If serotonin isn’t the answer, then what is? Current science shows strong evidence of things that work to improve brain health that aren‘t drugs.

Current and evolving science points to a linchpin of the neurological system. It’s the fine balance between the two neurotransmitters GABA and glutamate. It’s called the glutamate hypothesis. Understanding this could be the most important thing you ever do for your mental wellbeing. 


The glutamate hypothesis

The glutamate hypothesis is about when glutamate gets over-released, and the GABA -glutamate balance is affected. It’s not the only factor in brain health, for sure, but there’s evidence that it is a central part of being mentally well. 

Glutamate is released when you are excited. This means when you are stressed it floods out. In evolutionary terms, this was the occasional short burst of ‘fight or flight’ when the sympathetic nervous system gave you all the tools to survive when life was at stake. 

Now, in the modern world, we can have this system turned up for hours, days, weeks and even months at a time.

How does that affect us? Well, when glutamate is constantly high, it over-stimulates a receptor on the next neuron called the NMDA receptor. This has two effects:

  • That receptor starts to get dialled down and needs more and more glutamate to get activated.
  • All this extra glutamate spills over outside the cells. This glutamate is toxic and damages the nerves, synapses and supporting cells.

Normally, there are processes in the brain for managing glutamate and removing and recycling it. But when things are not working as they should, when the system gets out of whack and is not cycling properly – meaning that glutamate levels are getting too high – it is called excitotoxicity.

The glutamate continues to be overproduced and continues to spill over. Sometimes cells end up dying and the high concentrations of glutamate inside the cell are released creating even more excitotoxicity and killing more cells and releasing more glutamate – and the cycle continues.


What can we do to reduce glutamate?

The 7 levers of PreKure’s Mental Wellbeing 21-day plan are thought to be protective or helpful in reducing glutamate, by either helping remove it or reducing it.

1.    What we eat

Any nutrient which reduces inflammation in the brain is helpful for better mental wellbeing, e.g. antioxidants; Omega 3 fats; having ketones present in the brain; keeping blood sugar and insulin under control; avoiding MSG; avoiding too much alcohol.

2.    How much we exercise

Exercise is a mood modulator, and highly effective and curative in managing brain health, including depression and anxiety. 

3.    Sleep quality and quantity

Sleep is anti-inflammatory. Deep non-REM sleep activates the glymphatic system which removes waste products and reduces inflammation in the brain.

4.    Cold water immersion

There is evidence that cold water immersion is effective in changing mood and reducing anxiety and depression.

5.    Breathing – being calm

Breathing slowly and deeply through the nose results in the baroreflex being invoked. It turns off the ‘fight or flight’ sympathetic nervous system and can help reduce stress.

6.    Self-talk medicine

Identifying the negative voice in your head, the ‘saboteur’, and learning to do positive self-talk has a positive effect on brain health.

7.    Joy 

Finding and doing something that brings you joy every day.


Bringing it all together

The good news is, all these things work together. For example, eating better helps you sleep better. A good night’s sleep helps you make better food choices and be more likely to exercise. Exercise makes you tired and you will sleep better. Exercising outside raises Vitamin D levels and gets melatonin, the sleep hormone, properly regulated, and that helps everything in your brain. 

One way of getting the best bang for your buck is to package up activities together, and choose several of the things that are helpful for reducing glutamate in the brain.

You might decide exercise is really going to help you. But how about making sure you do it outside, with someone else, and it’s an activity and place that really brings you joy? How about trying some cold water immersion, but practicing your nose breathing and positive mantra at the same time?


Learn more

Read the white paper The Biology of Mental Health and Wellbeing here.

Are you interested in learning more about mental wellbeing? Sign up to PreKure’s Mental Wellbeing 21-day plan. Starts on the 3rd May 2021. Register here!


Need help now?

If you are feeling overwhelmed and don’t know where to turn, if you are having thoughts (or if someone you love is having thoughts) that make you afraid for your (their) life, then it is time to reach out. The following numbers may assist you.

New Zealand. If life is in danger, call 111. Or go to your nearest hospital emergency department. Or free call or text 1737 any time for support from a trained counsellor. 

Australia. If life is in danger, call 000. Or go to your nearest hospital emergency department. Or call 13 11 14 (Lifeline), call 1300 22 4636 (Beyond Blue), call 1300 659 467 (Suicide Call Back Service)