5 Common Causes of Depression

Depression, anxiety, and other mental health disorders are associated with disturbances in several biological processes in the body. These are summarised in the figure above and include:

1. Neurotransmitter imbalances

2. Dysregulated stress response

3. Chronic, low-grade inflammation

4. Excess free radical damage

5. Neuroprogression

Each of these processes all affects each other which can lead to an escalation of problems over time. For example, inflammation affects neurotransmitter balance, increases free radical production, and reduces important proteins essential for the growth and plasticity of neurons. Excess free radical production also exacerbates inflammation, damages brain cells and influences neurotransmitter production. All these inter-relationships can lead to a snowballing effect where disturbances intensify over time.

There is no simple way to improve all these physiological processes and that is why a multi-targeted, integrative approach is essential. Research has confirmed that many of these disturbances are influenced by psychological, dietary, environmental, and lifestyle factors, which is why changes covered in PI Therapy target these areas.

1. Neurotransmitter Disturbances

Neurotransmitters are chemicals that transmit signals across a synapse from one neuron (presynaptic neuron) to another, ‘target’, neuron (post-synaptic neuron). The neurotransmitter binds to a receptor on the post-synaptic neuron resulting in either an inhibitory or stimulatory action (neurotransmitters are stimulatory, inhibitory, or both). Neurotransmitters are important for cell-to-cell communication and too much, too little, or problems with receptors are associated with many diseases. Disturbances in neurotransmitter activity are the most popular biological theory for mental health problems, and the reason for the popularity of psychiatric medications, particularly antidepressants. The most common neurotransmitters implicated in depression are:

• Serotonin – low levels are believed to result in anxiety and depression.

• Dopamine – this is our feel-good neurotransmitter. Low dopamine levels are associated with depression, attention problems, and addictions. High dopamine is linked with bipolar disorder and schizophrenia.

• Noradrenaline – low levels can lead to depression and attention problems, while high levels can increase anxiety.

2. Dysregulated Stress Response

Responding to stress is essential for our survival. It keeps us alive and helps us to respond instinctively to a stressor. This process, known as our ‘fight or flight’ response, helps us to deal with danger and is triggered by the communication between different organs in our body. Areas of our brain known as the hypothalamus and pituitary gland instruct our adrenal glands to release hormones (e.g., cortisol) to help our body respond to the stress. This communication pathway is known as our HPA axis (Hypothalamus-Pituitary-Adrenal axis). Cortisol has numerous functions in the body and typically during danger, helps our body to either ‘fight or flight.’

While this HPA axis response is imperative for our survival, many people with depression have a dysregulated HPA axis activity. This could mean an overactive HPA activity, leading to excess levels of cortisol circulating in the body. Alternatively, some people can have an underactive HPA axis activity, which leads to insufficient levels of cortisol. When it comes to our HPA axis, balance is the key, not too much or too little

3. Chronic, Low-Grade Inflammation

Inflammation is a necessary part of the body’s response to injury and infection. It consists of cellular responses that help protect us from pathogens (germs) such as bacteria, viruses, or fungi; external injuries like scrapes or foreign objects (for example a thorn in your finger); and exposure to chemicals or radiation. Without inflammation, we cannot fight disease or heal from infection or injury. An acute inflammatory response is associated with several signs including redness, swelling, pain, heat, and loss of function. However, depression is associated with chronic, low-grade inflammation. This inflammatory response can linger for months to years and may not be associated with any of the signs of acute inflammation. That is why it is often called ‘silent’ inflammation. Chronic inflammation can damage our bodily organs, with our brain being particularly susceptible.

4. Excess Free Radical Damage (Oxidative & Nitrosative Stress)

Free radicals are unstable molecules with an unpaired electron. They are produced during normal cellular metabolism and have several important functions in the body. For example, at low levels, free radicals are involved in our defence system to help fight against disease. However, at high levels, free radicals can cause damage to all our cells and organs. Excess free radical production can occur when we are exposed to a range of lifestyle and environmental factors. Fried foods, excess alcohol, tobacco smoke, pesticide exposure, excess sunlight exposure, and pollution all produce free radicals. High levels of stress and suffering from a medical disease such as diabetes, obesity, cancer, and/or cardiovascular disease can also increase free radicals. Many diseases are associated with increased inflammation which is also a potent inducer of free radical production.

To guard against free radicals, we require antioxidants. Antioxidants quench free radicals by donating an electron to stabilise the free radical. Antioxidants can be produced endogenously (within our body) or exogenously (outside our body). Endogenous antioxidants include many antioxidant enzymes such at superoxide dismutase, glutathione peroxidase, and catalase. Our body also produces antioxidants such as glutathione, alpha lipoic acid, and coenzyme Q10. We can also increase antioxidant levels in our body by consuming high-antioxidant foods. Vitamins C and E, selenium, zinc, and flavonoids are derived from an array of foods including fruits, vegetables, herbs, spices, nuts, and seeds.

Unfortunately, many people with depression have low circulating levels of antioxidants and produce too many free radicals. This may be due to dietary, lifestyle, and/or environmental factors. Genetics can also play a part as many people may have genes that do not produce antioxidant enzymes efficiently. When free radical production is greater than antioxidant defences, a state known as oxidative and nitrosative stress (O&NS) results. This leads to a deterioration in cellular and tissue activity over time. Our brain is particularly susceptible to the damaging effects of O&NS.

5. Neuroprogression

It was previously believed that when our brain is damaged, it is unable to repair itself. Whether the damage is from disease, an accident, or simply the process of normal ageing, neurons could not regrow. However, it has been confirmed that the brain is indeed plastic (known as neuroplasticity) and certain brain regions are able to regrow. Eating a healthy diet and engaging in regular physical activity are some ways to help rebuild the brain. This is because these activities increase levels of brain-building proteins known as neurotrophins. Neurotrophins are essential in supporting the growth, survival and differentiation of neurons. One neurotrophin important for brain support is known as brain-derived neurotrophic factor (BDNF). Levels of BDNF have been found to be lower in people with psychiatric disorders. As time progresses, having low levels of BDNF can negatively impact on the brain’s ability to build and repair itself. In fact, studies have indicated that as the number of depressive episodes increases in adults, neuronal degeneration increases. The balance between neuronal repair and growth from neurotrophins is overrun by brain degeneration, leading to a state of ‘neuroprogression’. Depression is associated with reductions in brain volume, and there are volumetric changes in various brain regions including the hippocampus, amygdala, prefrontal cortex, anterior cingulate, and basal ganglia.