Depression & the Gut: Are they linked & what is the link? Part 1: What Causes Depression

What causes depression

What causes depression? We’ve written about the gut-brain axis in relationship to other disorders such as anxiety and ADHD. In this week’s article on the gut-brain axis, we address depression and the gut. The gut and the brain are linked by the “gut-brain axis”, which regulates brain function and behavior (Chunlong Mu, 2016). For a full explanation of the gut-brain axis, please see our first article on anxiety and the gut which can be searched for in our blog.

The gut-brain axis plays a critical role in many neurological disorders. It affects neuropsychiatric disorders like anxiety, depression, schizophrenia and dementia (Kim YK, 2018), as well as neurodevelopmental disorders in children including autism, ADHD, learning disabilities, intellectual developmental disorder, motor disorders, and specific learning disorders (EPA, 2015)In this article, we will explore the link between depression and the gut-brain axis. Major depressive disorder, usually just called ‘depression’, refers to a psychological state characterized by a low mood and an aversion to activity. Depression is a widespread chronic medical illness that can affect thoughts, behaviors, feelings, mood, physical health and overall sense of well-being. Typical traits of depression are low mood, lack of energy, sadness, insomnia, and an inability to enjoy life.

Key facts about Depression:

What Causes Depression?

A person’s susceptibility to depression and other mental health issues depends on genetic and epigenetic (i.e. social and environmental) factors. These factors are connected, as epigenetics can activate a genetic predisposition.

Like many of the complex conditions we have written about (anxiety, ADHD, autism, fibromyalgia, hypertension), there is not one single cause of depression. Instead many possible causes of depression exist. Conventional wisdom says that depression is genetic and caused by a chemical imbalance in the brain. This may be true but there are other, possibly surprising, causes of depression; for example, blood sugar imbalance, inflammation and poor gut health. Other factors may be stress, trauma, medications and illness.

  • GENETIC VULNERABILITY: Family and twin studies show strong evidence that genetic factors contribute to the risk of depression (Shadrina M, 2018). One study using twin research data shows that the heritability rate for depression is 37% (Shadrina M, 2018). Data from family studies show a 2 to 3-fold increase in the risk of depression in children of parents with depression (Shadrina M, 2018). Heritability is especially relevant in the more severe forms of depression (Shadrina M, 2018).The severity of a person’s depression depends on whether it is inherited from the mother or father’s side (Shadrina M, 2018).
  • A CHEMICAL OR NEUROTRANSMITTER IMBALANCE in the brain: Neurotransmitters are naturally occurring brain chemicals that likely play a role in depression. Recent research indicates that changes in the function and effect of these neurotransmitters and how they interact with neurocircuits involved in maintaining a stable mood may play a significant role in depression and its treatment (Mayo Clinic, 2019).
  • HORMONES: Changes in the body’s balance of hormones may be involved in causing or triggering depression. Hormone changes can result with pregnancy and during the weeks or months after delivery (postpartum) and from thyroid problems, menopause or a number of other conditions (Mayo Clinic, 2019)
  • STRESSFUL LIFE EVENTS & TRAUMA: Chronic stress and stressful life events are strong predictors of the onset of depression (Shadrina M, 2018). Prolonged activation of the stress response system of the body can cause a higher risk of obesity, heart disease, depression and other disorders (Shadrina M, 2018). Many studies have looked at the link between Adverse Childhood Experiences (ACEs) and mental and physical health in later life as an adult. ACEs are defined as childhood abuse, neglect, psychological stress, being spanked as a child, sexual abuse, violence against mother, living with household members who were substance abusers and general household dysfunction (Felitti VJ, 1998). People who reported experiences of childhood adversity, compared to those who had experienced none, had increased health risks for alcoholism, drug abuse, depression, and suicide attempt; an increase in smoking, poor self-rated health, increase in physical inactivity, risky sexual behavior and sexually transmitted disease (Felitti VJ, 1998). Being spanked as a child was significantly associated with self-reported mental health issues (Merrick MT, 2017). Generally speaking, the more ACEs a person has experienced, the greater impact it has on health in adult life, with a higher incidence of mental health issues such as depression (Felitti VJ, 1998).
  • BLOOD SUGAR IMBALANCES: Blood sugar, or glucose, imbalances can cause mood issues. We have seen this clinically in our practice. Over time, a glucose imbalance will also lead to insulin resistance. Multiple studies have found that blood sugar disturbances and insulin resistance are closely associated with depression (Peng YF, 2017), (Lee JH, 2017) and (Timonen M, 2005).
  • POOR DIET: An unhealthy diet has recently emerged as a significant risk factor for depression (Dash S, 2015). Nutrition can play a key role in the severity and duration of depression as well as in the risk of becoming depressed in the first place (Sathyanarayana TS, 2008). Depressed people tend to have a poor appetite, skip meals, and eat excessive amounts of sweet foods. These dietary habits have been observed both during a depressive episode and before the depressive episode, indicating that poor nutrition is a risk factor (Sathyanarayana TS, 2008). Nutrient deficiencies can contribute to depression and are often seen in depressed people. The most common nutritional deficiencies seen in patients with mental disorders are: omega 3 fatty acids, B vitamins, minerals, and the amino acids that are precursors to neurotransmitters (Sathyanarayana TS, 2008). In addition to creating nutrient deficiencies and causing blood sugar highs and lows, an unhealthy diet causes systemic inflammation and is negative for gut health. As you read on, you will see that inflammation and gut health are key factors in the incidence of depression.
  • MEDICATION & MEDICAL PROBLEMS: Certain medications can have side effects that include mood disorders like depression (Harvard Health Publishing, 2019). Also, having serious medical problems, a life-threatening diagnosis or disease can affect one’s mood and be a potential epigenetic trigger that may bring on depression (Harvard Health Publishing, 2019).

Newer research has looked at inflammation and gut health as leading causes of depression:

What Causes Depression? INFLAMMATION:

There is ample data supporting the role of inflammation in depression (Miller AH, 2016). Patients with major depressive disorder exhibit all of the classic features of an inflammatory response, including increased amounts of inflammation-related cells of the immune system (Miller AH, 2016).

One study found that hs-CRP (high sensitivity C-reactive protein) is a reliable indicator of depression. Hs-CRP is a marker found in blood testing that indicates the level of systemic inflammation in the body. This study linked higher levels of hs-CRP in participants with depression (Pasco JA, 2010). Thus systemic inflammation is a risk factor for depression.

Further evidence was found in a study looking at post-mortem brain samples from suicide victims that had depression (Miller AH, 2016). Researchers saw an increase of various inflammatory proteins and other molecules in the brain samples (Miller AH, 2016).

In addition, giving inflammatory cytokines (inflammation-related molecules of the immune system) to non-depressed people causes symptoms of depression (Miller AH, 2016). In contrast, blocking these cytokines has been shown to reduce depressive symptoms in patients with medical illnesses, including major depressive disorder (Miller AH, 2016).

These inflammatory cytokines affect neurotransmitters and neurocircuits of the brain, leading to behaviors that are classified as depressive (Miller AH, 2016). Thus, the faulty brain chemistry observed in depression is, at least in part, a consequence of increased inflammation in the brain.

What Causes Depression? GUT HEALTH:

As we outlined in our first article of the Gut-Brain Axis series on anxiety, gut health is fundamental to brain health. The vagus nerve, the HPA axis, neurotransmitter status, short chain fatty acids and the immune system all impact the brain and can, if out of balance, cause mood-related issues. For a review of these factors, please see our anxiety article here.

One study looked at the specific bacteria strains found in the guts of depressed people and healthy, non-depressed people (Jiang H, 2015). There were material differences in the bacteria composition of the two groups. In the depressed patients, there was either a majority of some potentially harmful bacterial groups or a reduction in beneficial bacterial groups, when compared to non-depressed people (Jiang H, 2015).

Another study out this year, 2019, has found that people with lower levels of a specific gut bacteria called Bacteriodes enterotype 2 reported a lower quality of life and a tendency toward depression (Valles-Colomer M, 2019). People in the survey who reported a higher quality of life had higher levels of two other types of gut bacteria, Faecalibacterium and Coprococcus (Valles-Colomer M, 2019). These two bacteria strains produce the short chain fatty acid butyrate, which is known to reduce inflammation (Valles-Colomer M, 2019).

The gut is critical to depression as certain bacteria can reduce inflammation and, as a result, depression, given that depression is an inflammatory disorder.

Any GI infections or overgrowths will be an issue because they cause inflammation of the gut. This could be issues like dysbiosis, SIBO, candida, parasites, leaky gut, food sensitivities, histamine intolerance or others. We know that these issues cause gut inflammation, so therefore will potentially contribute to depression.

Improving gut health through probiotics can play a major role in the communication between the gut and the brain (Huang R, 2016). Multiple studies have looked at probiotics’ effect on mood and depression and probiotics were associated with a significant reduction in depression (Huang R, 2016).


Many treatment strategies for depression exist, including pharmaceuticals such as selective serotonin reuptake inhibitors (SSRIs) and lithium; medical technologies such as electroconvulsive therapy, deep brain stimulation, and bright light therapy, exercise, and music therapy.

However, approximately 33% of all patients with depression fail to respond to conventional antidepressant therapies (Miller AH, 2016). Medication may be significant in only the most severely depressed individuals (Huang R, 2016). There is other data suggesting that antidepressants are not as effective as the marketing of these drugs suggests (Ioannidis, 2008). Short-term benefits are small and the long-term balance of benefits and harms is not well documented (Ioannidis, 2008).

Side effects of antidepressants exist and can be serious. It has recently come to light that suicidal ideation and completion is a side effect of antidepressant drugs. One study found that as prescriptions of antidepressant drug have increased over time, so has the suicide rate (Larsson, 2017). In fact, 52% of the study subjects who committed suicide were prescribed antidepressants within a year of committing suicide (Larsson, 2017). Antidepressants were detected in 41% of the study subjects who committed suicide, indicating that they were under the influence of antidepressants at the time of death (Larsson, 2017).

Clearly, there is room for improvement in the treatment of depression. Please tune in next week to Part 2 of Depression and the Gut, where we will provide specific ways to address depression through functional medicine.

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