What is anxiety?

Anxiety is a normal reaction to stress and can be beneficial in some situations. It can alert us to danger and help us prepare and pay attention. Anxiety disorders differ from normal feelings of nervousness or anxiety and involve excessive fear or anxiety. They are the most common form of mental illness, affecting almost 30% of adults in their lifetime.

What is depression?

Depression is among the most common and costly psychiatric illnesses. Nearly one in four women and one in six men will experience depression during their lifetime, and up to 65% of individuals have recurrent episodes of the disorder. The WHO characterizes depression by: persistent sadness and a lack of interest or pleasure in previously rewarding or enjoyable activities. It can also disrupt sleep, appetite and concentration.

Anxiety, sadness and fear are all normal emotions designed to help us protect ourselves, so under what circumstances do these normal emotions lead to anxiety disorders and/or depression?

Research has now shown that stressful events or ongoing psychological stress increase inflammatory components of the immune system, leading to increases in long-term chronic inflammation. This is believed to be a major driver of depression. Increases in inflammation can in turn trigger profound changes in behaviour, including the onset of anxiety and depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation and social-behavioural withdrawal.

In particular, social stressors involving conflict, threat, isolation and rejection have been shown to increase inflammatory markers including IL-6, TNFα and CRP.

The main factor that determines the onset of inflammation is the perception of stress. People who perceive stress as helpful or who do not consider the same situation as a negative stressful event have a reduced inflammatory response compared to those who perceive the event as negatively stressful.

Inflammation certainly plays a role in the pathogenesis of anxiety and depressive disorders, directly through neuroinflammation and degeneration. However, this is not the only mechanism by which inflammation, particularly via caspase-1 activation, influences mood disorders. It has been shown that when caspase-1 is inhibited, changes in the gut microbiota are observed, including an increase in the relative abundance of Akkermansia spp. and Blautia spp., which are consistent with the beneficial effects of attenuated inflammation.4

Inflammation and the gut

Inflammation also influences mood disorders by inducing changes in the gut microbiome. These changes that occur are complex and not yet fully understood. However, depression is consistent with specific changes in the gut flora. More than 70% of the microbiome comes from the two most prominent phyla Firmicutes and Bacteroides, while Proteobacteria, Actinobacteria, Fusobacteria and Verrucomicrobia are present in reduced numbers. For example, patients diagnosed with major depressive disorder (MDD) have a different fecal microbiome composition compared to healthy controls: MDD patients showed an increase in Bacteroidetes, Protobacteria and Actinobacteria, and less Firmicutes. Furthermore, across genera, these patients showed an increase in Enterobacteriaceae and Allistipes, and less Faecalibacterium, the latter of which inversely correlated with depression severity.

Similar effects are observed in anxiety disorders, where the fecal microbiota of patients suffering from generalized anxiety disorder (GAD) showed a much lower prevalence of five genera: Faecalibacterium, Eubacterium rectale, Lachnospira, Butyricicoccus and Sutterella. These are thought to be relevant to mental health due to their documented production of short-chain fatty acid (SCFA) compounds. SCFAs are essential for supporting the integrity of the digestive lining, as well as the blood-brain barrier and stimulation of the vagus nerve (the nerve that connects the gut to the brain), which could be one mechanism by which these changes trigger effects on mood and anxiety.

In addition, psychological stress and changes in bacterial diversity can increase intestinal permeability and allow bacterial liposaccharides (known as endotoxins) to enter the bloodstream when an immune response is initiated. This peripheral inflammation can spread to the central nervous system (CNS) in a number of ways and thus affectr mental health by promoting neurotoxins and hindering neurotransmitters.5,6

Vicious cycle

There is a cycle that occurs that can be difficult to break, where stress itself can trigger anxiety and lead to inflammation (which in itself causes neurodegeneration and neuroinflammation), which disrupts the microbiome and affects neurotransmitter production, as well as signaling to the brain via the vagus nerve, and additionally increases gastrointestinal permeability, which increases inflammation and can disrupt the blood-brain barrier leading to more neuroinflammation. In concert, all of these factors can affect physiological stress, which is increased by inflammation and gastrointestinal disturbances, but also neuroinflammation can disrupt the way we perceive stress, and so it is a vicious cycle.

Although depressive and anxiety disorders manifest in different ways and may involve dysregulation of different neurotransmitters, the pathogenesis is very similar in most anxiety and depressive disorders. It’s important to realise that many antidepressant medications have been shown to increase anxiety at least in the short term (and conversely, anti-anxiety medications can predispose to depression as they “depress” the CNS). It’s therefore useful to identify this as it’s likely that different neurotransmitters are involved, but also as these two are strongly linked they should not be treated exclusively and balance is key.

How to Help

Exercise – exercise is important for mental and emotional wellbeing as it can increase feel-good endorphins as well as improving stress resilience.

Be grateful – gratitude journals have been shown to help improve measures of stress and depression. One study showed that people who were asked to record five things they were grateful for that had happened in the past week were 25% happier than those who either didn’t do it or recorded negative emotions.

Acts of kindness – something that has been shown to improve our mood and wellbeing is acts of kindness. Practicing kindness also has a profound effect on our mental and physiological health, helping us become happier and more compassionate towards others. Being kind to others is known to help boost our own immune system, slow down aging, increase our self-esteem, and improve blood pressure.

In many cases, additional medical help, such as psychotherapy and cognitive behavioral therapy, may be necessary.

Nutritional interventions

Nutritional interventions to consider should include methods to reduce inflammation, support the microbiome, and support gastrointestinal integrity. Therefore, gut health should always be considered for those suffering from depression:

Consider supporting a healthy gut flora:

Take a live bacteria supplement - taking probiotics and prebiotics has been shown to decrease

the stress response during difficult tasks, improve gut barrier integrity, and decrease inflammation. There is considerable evidence to suggest that these improvements, among other effects, may contribute to decreased anxiety- and depression-like behaviors in mice

Consuming fermented foods such as kefir, kombucha, sauerkraut, and miso

Consuming prebiotic foods (fuel for gut bacteria) and polyphenols from chicory, olives, baked apples, and Jerusalem artichokes

Research has shown that nutrients important for the repair and integrity of the digestive lining include:

Vitamin A

Vitamin D3

L-Glutamine

Zinc

In addition, reducing inflammation should be considered:

How to reduce inflammation:

Optimizing gut health

Reducing omega-6 fatty acids from meat, dairy, and vegetable oils

Increasing omega-3 fatty acids from oily fish, chia and flax seeds, and dark green leafy vegetables

Using anti-inflammatory foods such as turmeric (curcumin) and ginger

Increase vitamin E containing foods such as avocado

Increase foods rich in Vit C

General interventions

B6 and magnesium which convert 5HTP to serotonin

Gut health, suspect leaky gut and/or dysbiosis and consider a probiotic

Inflammation consider an anti-inflammatory diet as well as anti-inflammatory nutrients such as Omega 3 fats (such as EPA), curcumin and ginger

Supports antioxidant status and reduces oxidative stress

Additional vitamin D3, zinc and methylation support (e.g. methylfolate and methylcobalamin) are needed

Reference

1 - Tiller JW (2013) ‘Depression and anxiety’, Med J Aust, 99(S6) S28-S31.

2 - Slavich GM, Irwin MR (2014) ‘From stress to inflammation and major depressive disorder: a social signal transduction theory of depression’, Psychol Bull, 140(3) pp774-815.

3- Lee JS, Joo E, Choi KS (2012) ‘Perceived Stress and Self-esteem Mediate the Effects of Work‐related Stress on Depression’, Stress nad Health, 29(1) pp75-81

4- Wong ML, Inserra A, Lewis MD, et al (2016) ‘Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition’, Mol Psychiatry, 21(6) pp797-805.

5- Jason M. Peirce K (2019) ‘The role of inflammation and the gut microbiome in depression and anxiety’, Journal of Neuroscience Research, 97(10) pp1223-1241

6 - Jacobson, N. C., & Newman, M. G. (2017) ‘Anxiety and depression as bidirectional risk factors for one another: A meta-analysis of longitudinal studies’, Psychological Bulletin, 143(11) pp1155–1200

7 - Sibelli A, Chalder T, Everitt H, Workman P, Windgassen S, Moss-Morris R (2016) ‘A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset’, Psychol Med, 46(15) pp3065-3080.

8 - https://www.sciencedaily.com/releases/2016/08/160824135045.htm

9 - https://www.addictioncenter.com/drugs/drug-classifications/central-nervous-system-depressants/