Your mental health is an important part of your well-being. This aspect of your welfare determines how you’re able to operate psychologically, emotionally, and socially among others.

Considering how much of a role your mental health plays in each aspect of your life, it's important to guard and improve psychological wellness using appropriate measures. Fortunately, with increasing awareness, there is a lot more consideration around research and funding for addressing mental health disorders and it is getting the attention it deserves. This is leading to new ideas and therapies and hopefully over time can start to make an impact on global well-being.

What Is Depression?

Depression (major depressive disorder) is a common and serious medical illness that negatively affects how you feel, the way you think and how you act. Fortunately, it is also treatable. Depression causes feelings of sadness and/or a loss of interest in activities you once enjoyed. It can lead to a variety of emotional and physical problems and can decrease your ability to function at work and at home.

Depression symptoms can vary from mild to severe and can include:

• Feeling sad or having a depressed mood
• Loss of interest or pleasure in activities once enjoyed
• Changes in appetite — weight loss or gain unrelated to dieting
• Trouble sleeping or sleeping too much
• Loss of energy or increased fatigue
• Feeling worthless or guilty
• Difficulty thinking, concentrating or making decisions

For a diagnosis of depression, symptoms must last at least two weeks and must represent a change in your previous level of functioning. Also, medical conditions (e.g., thyroid problems, a brain tumour or vitamin deficiency) can mimic symptoms of depression so it is important to rule out general medical causes.

Depression affects an estimated one in 15 adults (6.7%) in any given year. And one in six people (16.6%) will experience depression at some time in their life. Depression can occur at any time, but on average, first appears during the late teens to mid-20s. Women are more likely than men to experience depression. Some studies show that one-third of women will experience a major depressive episode in their lifetime. There is a high degree of heritability (approximately 40%) when first-degree relatives (parents/children/siblings) have depression.

Up to 30% of people with depression don’t respond to treatment with antidepressants. This may be down to differences in biology between patients and the fact that it often takes a long time to respond to the drugs – with some people giving up after a while. So there is an urgent need to expand the repertoire of drugs and/or alternate therapies to people with depression.

There is a lot of research being done and some exciting new ideas coming to the fore in this space. These include techniques such as repetitive transcranial magnetic stimulation (rTMS), further understanding and emerging products in the nutritional space, and more evidence and destigmatisation when it comes to the therapeutic potential of psychedelic compounds.

Risk Factors for Depression

Depression can affect anyone—even a person who appears to live in relatively ideal circumstances. Several factors can play a role in depression:

• Biochemistry: Differences in certain chemicals in the brain may contribute to symptoms of depression.
• Genetics: Depression can run in families. For example, if one identical twin has depression, the other has a 70 percent chance of having the illness sometime in life.
• Personality: People with low self-esteem, who are easily overwhelmed by stress, or who are generally pessimistic appear to be more likely to experience depression.
• Environmental factors: Continuous exposure to violence, neglect, abuse or poverty may make some people more vulnerable to depression.

Novel techniques for treating depression

Although the technology has been around for close to 20 years researchers have shown, for the first time, what happens to the brain when a person receives a depression treatment known as repetitive transcranial magnetic stimulation (rTMS). The results out of the University of British Columbia were published recently in the American Journal of Psychiatry.

rTMS is a depression treatment typically used when other approaches—such as medications—haven’t been effective for a patient. As mentioned, it is estimated that approximately 30 percent of people with major depression do not respond to antidepressants. During an rTMS session, a device containing an electromagnetic coil is placed against a patient’s scalp. The device then painlessly delivers a magnetic pulse that stimulates nerve cells in a region of the brain involved in mood control—called the dorsolateral pre-frontal cortex. Although proven to be effective, the mechanisms behind how rTMS affects the brain have not been well understood.

Dr. Vila-Rodriguez and his team delivered one round of rTMS to patients while they were inside a magnetic resonance imaging (MRI) scanner. Since the MRI can measure brain activity, the researchers were able to see in real time what changes were happening in the brain. The team found that by stimulating the dorsolateral pre-frontal cortex, several other regions of the brain were also activated. These other regions are involved in multiple functions—from managing emotional responses to memory and motor control.

The participants then underwent another four weeks of rTMS treatment and the team assessed whether the activated regions were associated with patients having fewer symptoms of depression when their treatment ended. “We found that regions of the brain that were activated during the concurrent rTMS-fMRI were significantly related to good outcomes,” says Dr. Vila-Rodriguez. This shows that there were structural changes in the brain as a result of the stimulation, allowing more activity and therefore more blood flow to areas associated with positive mood.

In recent years, attention has turned to psychedelics such as psilocybin, the active compound in “magic mushrooms”. Despite a number of clinical trials showing that psilocybin can rapidly treat depression, including for cancer-related anxiety and depression, little is known about how psilocybin actually works to relieve depression in the brain.

Now two recent studies, published in The New England Journal of Medicine and Nature Medicine, have shed some light on the mechanism.

Psilocybin is a hallucinogen that changes the brain’s response to a chemical called serotonin. When broken down by the liver (into “psilocin”), it causes an altered state of consciousness and perception in users. Previous studies, using functional MRI (fMRI) brain scanning, have shown that psilocybin seems to reduce activity in the medial prefrontal cortex, an area of the brain that helps regulate a number of cognitive functions, including attention, inhibitory control, habits and memory. The compound also decreases connections between this area and the posterior cingulate cortex, an area that may play a role in regulating memory and emotions. An active connection between these two brain areas is normally a feature of the brain’s “default mode network”. This network is active when we rest and focus internally, perhaps reminiscing about the past, envisioning the future or thinking about ourselves or others.

By reducing the activity of the network, psilocybin may well be removing the constraints of the internal “self” – with users reporting an “opened mind” with increased perception of the world around them. Interestingly, rumination, a state of being “stuck” in negative thoughts, particularly about oneself, is a hallmark of depression. And we know that patients with higher levels of negative rumination tend to show increased activity of the default mode network compared with other networks at rest – literally becoming less responsive to the world around them.

The most compelling evidence of how psilocybin works comes from a double-blind randomised controlled trial (RCT), that compared a group of depressed people taking psilocybin with those taking the existing antidepressant drug escitalopram – something that’s never been done before. The trial was further analysed using fMRI brain scans, and the results were compared with other fMRI findings from another recent clinical trial.

Just one day after the first dose of psilocybin, fMRI measures revealed an overall increase in connectivity between the brain’s various networks, which are typically reduced in those with severe depression. The default mode network was simultaneously reduced, while connectivity between it and other networks was increased – backing up previous, smaller studies.

The dose increased connectivity more in some people than others. But the studies showed that the people who had the biggest boost in connection between networks also had the greatest improvement in their symptoms six months later.

The brains of people taking escitalopram, on the other hand, showed no change in connectivity between the default mode and other brain networks six weeks after treatment started. It is possible that escitalopram may bring about changes at a later time point. But the rapid onset of psilocybin’s antidepressant effect means it may be ideal for people who don’t respond to existing antidepressants.

The study proposes that the observed effect may be due to psilocybin having more concentrated action on receptors in the brain called serotonergic 5-HT2A receptors, than escitalopram. These receptors are activated by serotonin and are active throughout network brain areas, including the default mode network. We already know that the level of binding by psilocybin to these receptors leads to psychedelic effects and are likely responsible for some of these mood-boosting effects.

This 12-week RCT, conducted by researchers from the University of Technology Sydney, was recently published in the peer-reviewed American Journal of Clinical Nutrition.

Lead researcher Jessica Bayes, a PhD candidate in the UTS Faculty of Health, said the study was the first RCT to assess the impact of a Mediterranean diet on the symptoms of depression in young men (aged 18-25). It suggests that medical doctors and psychologists should consider referring depressed young men to a nutritionist or dietitian as an important component of treating clinical depression

There are lots of reasons why scientists think food affects mood. For example, around 90 per cent of serotonin, a chemical that helps regulate mood, is made in our gut, by our gut microbes. There is emerging evidence that these microbes can communicate to the brain via the vagus nerve, in what is called the gut-brain axis.

The key feature of this work was nearly all participants stayed with the program, and many were keen to continue the diet once the study ended, showing how effective, tolerable and worthwhile they found the intervention.

How can Ārepa help?

Ārepa operates at the nexus between neuroscience, nutrition, and technology. It is formulated by a world-leading neuroscientist to provide a novel combination of ingredients that work in conjunction to support brain health and therefore mental health. The active ingredients help to provide both acute and chronic relief from a range of health deficits. The potent antioxidant and anti-inflammatory properties of both the New Zealand blackcurrant (Neuroberry) and the pine back extract (Enzogenol) help promote new blood vessel and new nerve cell growth. This can help positively modulate the levels of certain neurotransmitters and hormones, directly regulating mood.

Additionally, L-theanine has shown a plethora of clinical evidence in altering brain wave activity to create a calm, clear and focused mental state. This operates on an acute timescale and can interrupt the dangerous cycle of rumination so often coincident with depression and mental health issues. L-theanine also functions in similar fashion to the neurotransmitter glutamate, helping it to have anxiolytic properties, relieving anxiety and helping performance and productivity under stress.

Ārepa contributes to the variety of new innovations and ideas using science to find alternate ways to help treat depression when conventional methods are unsuccessful. Seeing a range of techniques being researched and employed to treat the array of complex and detrimental mental health disorders is incredibly encouraging.

Got a question for Sam, our in-house Neuroscientist? Email sam@drinkarepa.com