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The Functional Medicine Approach to Depression: Identifying and Treating the Root Cause


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In 2017, more than 17 million American adults reported experiencing at least one major depressive episode. (1) In 2020, as we deal with the COVID-19 pandemic, racial injustice, and increased stress and uncertainty, those numbers appear to be rising. According to one study, stressors related to the pandemic led to a three-fold increase in the rates of depression across all demographic groups studied. (2) If you’re struggling, you’re not alone. Embracing a root-cause-based Functional Medicine approach to depression may help you get relief, potentially without the use of antidepressants.

Functional Medicine depression
The Functional Medicine approach to depression involves identifying the root cause, like chronic stress or sleep deprivation. iStock/PeopleImages

While antidepressants can be life-saving for some people—and, if you’re currently taking antidepressants, you should not stop doing so without the guidance and support of your doctor—they’re not a good fit for everyone. For some people, they don’t alleviate depressive symptoms, and for others, they cause a new set of disruptive side effects. Other people don’t want to take antidepressants long-term or they can’t afford the financial investment to do so. Whatever your reason, there is a way to address the root cause of your depression directly, without long-term antidepressant usage: Functional Medicine.

The Functional Medicine approach to depression—and in fact, the Functional Medicine approach to any chronic condition—is to identify and address the root cause of the problem. That means treatment is focused on fixing the reason for your depression, whether that’s gut dysbiosis, chronic stress, infection, or another of the 10 possible causes I discuss below. Keep reading for more information on what could be causing your depression and how a Functional Medicine-based approach can help.

What’s the root cause of depression? Check out this article for 10 possible causes and find out what you can do to alleviate your symptoms and get help. #functionalmedicine #chriskresser

The Conventional Treatment for Depression: Antidepressants

Depression takes a heavy toll on physical health, day-to-day functionality, and relationships. It causes symptoms like: (3)

  • Profound feelings of sadness
  • Hopelessness
  • Fatigue
  • Feelings of guilt or worthlessness
  • A loss of interest in activities
  • Changes in sleep and appetite patterns
  • Irritability
  • Difficulty concentrating
  • Moving or talking more slowly than normal
  • Restlessness
  • Unexplained aches, pains, cramps, headaches, and even digestive problems
  • Thoughts of death or suicide

And while some people may experience just one depressive episode in their lives, multiple episodes are common. (4)

Antidepressants are the most common conventional treatment for depression. In fact, between 2011 and 2014, one in eight Americans aged 12 and up reported taking an antidepressant the previous month. (5)

Some research suggests that antidepressants are not as effective as they’re often claimed to be. Initial treatment may be effective at mitigating symptoms only around half the time, and antidepressants may not have any benefit over placebo for mild and moderate depression. (6, 7, 8, 9, 10) What’s more, these drugs can also cause side effects, like: (11)

  • Anxiety
  • Decreased libido
  • Nausea
  • Weight gain
  • Dry mouth
  • Constipation
  • Dizziness
  • Tiredness and/or insomnia
  • Sweating
I’m not here to say that antidepressants have no place in treating depression. That’s because, for some people, they are effective at alleviating their symptoms without causing worrying side effects. Put simply, they work for them. But unfortunately, that isn’t true for everyone, and even if they do relieve symptoms, antidepressants do nothing to address the underlying cause of depression.

For those of you who haven’t found relief in antidepressants, a Functional Medicine-based psychiatric approach may offer the help you’re looking for. And a key component to that approach? Identifying the root cause of your depression. 

Do you want to learn more about how to apply a Functional Medicine approach to healthcare? If you’re a licensed practitioner, the ADAPT Practitioner Training Program can help you learn how to implement a patient-centered, holistic, investigative approach in your practice. Click here to find out more.

10 Root Causes of Depression

Most of us are familiar with the conventional explanation for depression: the chemical imbalance theory. This theory states that depression is caused by imbalanced neurotransmitters in the brain, and antidepressants are needed to manipulate the levels of those neurotransmitters—which should, in theory, correct the problem.

There’s quite a bit wrong with the chemical imbalance theory—namely, research indicates that only 25 percent of people with depression have low levels of neurotransmitters, and others have high levels of them. (12) It also fails to recognize the link we see between chronic inflammation and depression. This means if you’re not part of that comparatively small group of people experiencing a neurotransmitter imbalance, antidepressants won’t correct the problem. For that, you’ll need to address the real root cause of your depression.

1. Blood Sugar Dysregulation and Obesity

Insulin influences your central nervous system, impacts neuronal circuitry formation, and affects synaptic plasticity—meaning it plays an important role in your mental health. If your blood sugar is dysregulated and you’re experiencing insulin resistance, your brain will feel the effects along with the rest of your body, and anxiety and depression may result. (13, 14)

Obesity is closely tied with blood sugar dysregulation and depression. This connection is likely multifactorial and complex; but, as obesity is an inflammatory state, and we see evidence that people with obesity have higher levels of inflammatory signaling molecules called cytokines, it’s probable that inflammation plays a critical role in the obesity-depression connection. (15, 16)

2. Chronic Stress

Chronic stress can also have an inflammatory effect on your body. Your nervous system mediates inflammation and the body’s immune response; if something goes awry, depression, anxiety, and other mood imbalances can result. (17, 18, 19)

The relationship between your stress levels and your hypothalamus–pituitary–adrenal (HPA) axis is complex. In a healthy relationship, an acutely stressful event should spur your sympathetic nervous system into action, triggering the HPA to release stress hormones to help you respond to the stressor. After that event, your parasympathetic nervous system should take over, decreasing activity in your HPA axis and reducing stress hormone production. (20) However, if you’re experiencing chronic stress, your sympathetic nervous system and HPA axis can remain chronically activated, causing a host of health problems (depression included).

Your HPA axis also acts on your thyroid gland—any stress-related disruption in HPA axis function could lead to problems with your thyroid, which can also cause symptoms of depression.

3. Environmental Factors

Environmental toxins can also impact your mental health. Indoor mold exposure can trigger a complex inflammatory response that leads to several cognitive side effects, including depression. (21, 22) Mold exposure can trigger the release of inflammatory cytokines and impair neuronal plasticity (which can both lead to symptoms of depression). (23, 24, 25)

Air pollution is another toxin that can impact mental health (and your overall well-being and longevity). Ambient air pollution can lead to neuroinflammation, which increases the risk of depression. Those effects appear to be especially significant for people who encountered air pollution during the first 10 years of their lives. (26)

Some research also suggests that radiation produced by electromagnetic fields (EMFs) may also have a connection with depression. EMFs may contribute to depression by changing the activity of voltage-gated calcium channels in the brain. This can lead to a host of neuropsychiatric symptoms, like fatigue, headaches, insomnia, irritability, and a depressive mood. (27, 28)

4. Genetics

Certain genetic variants are potentially associated with depression:

  • The methylenetetrahydrofolate reductase (MTHFR) gene: Variants in the MTHFR gene are linked to depression (as well as anxiety, autism, and schizophrenia). (29)
  • The glutamic acid decarboxylase (GAD) gene: GAD variants may decrease the conversion of glutamate to gamma aminobutyric acid (GABA), which can result in major depressive disorder. (30)

I want to note here that our understanding of the genetic risks associated with depression is far from complete. If you have one of these variants, take that information with a grain of salt—consumer genetic testing has its own potential pitfalls, and your genes aren’t the only factor that influences your health. Often, the exposome (all of those external health determinants like your diet, lifestyle, and environment) is the primary driver behind your overall well-being.

5. Infection

Research suggests that several chronic infections are associated with depression, including:

The mechanism behind this connection could be described by the pathogen-host defense theory of depression (credit to the very forward-thinking Dr. Charles Raison for this theory). According to this idea, some of the behavioral symptoms of depression may actually be behavioral responses to infection, suggesting that human depression evolved out of sickness. (35, 36) Chronic infections are also associated with chronic inflammation, which is linked to symptoms of depression. (37)

6. Leaky Gut and Gut Dysbiosis

Your gut health impacts your mental health through the gut–brain axis. This axis transmits messages to and from the gut and the central nervous system via inflammatory mediators, gut microbial metabolites, stress hormones, neurotransmitters, and the vagus nerve. (38)

Intestinal barrier integrity and a balanced gut microbiome are two crucial components of a healthy gut—if these are disrupted, your gut health (and, potentially, your mental health) will be impacted.

Leaky gut is a condition where the intestinal barrier allows undesirable and incompatible substances from the gut to “leak” into the bloodstream. This includes endotoxins called lipopolysaccharides, which provoke the release of inflammatory cytokines after entering the bloodstream. (39) Robust research also shows that changes in the makeup of our gut microbiome are associated with major depressive disorder. (40) Factors shown to disrupt the intestinal barrier and gut microbiota may increase the risk of future mental illness. (41)

7. Loneliness, Trauma, and Social Determinants of Health

Our social support system plays an enormous role in our ability to maintain our health. That can include our network of friends, loved ones, and family, and it’s impacted by social determinants of health, like our race and socioeconomic status.

Social isolation is linked with greater incidences of depression (among other serious health conditions), while those who have a strong social support network tend to have better health and lower levels of inflammation. (42, 43) Loneliness is linked with a higher risk of death, even after controlling for factors like physical health, alcohol consumption, and smoking. (44)

Trauma can also be a trigger for depression. Experiencing trauma during childhood (including even childhood bullying) can strongly predict future risk of depression and other mental health disorders, possibly by altering the function of the HPA axis long-term and contributing to chronic, systemic inflammation. (45, 46, 47) Trauma experienced during adulthood can also cause depression; that can include things like:

The COVID-19 pandemic can also be defined as a traumatic event in and of itself, and experiencing things like the death of a loved one, job loss, and financial trouble can all certainly be traumatic. (48, 49)

Social determinants of health also have a major impact on our risk level when it comes to developing depression. These can include:

  • Access to healthy food
  • Local air and water quality
  • Education
  • Neighborhood
  • Socioeconomic status
  • Education
  • Race
  • Gender

It’s well worth discussing these determinants of health now, as we grapple publicly with social justice and racism. Health and social inequality are connected—in fact, research shows that experiencing racism or even anticipating racist encounters contributes to chronic stress and low-grade inflammation, both risk factors for depression. (50, 51, 52)

8. Sedentary Lifestyle

Regular exercise is linked to good mental health, but a sedentary lifestyle is associated with depression in people of all ages. (53, 54) As an interesting side note, while exercise initially produces inflammatory cytokines (which are associated with depression), an induction of anti-inflammatory substances quickly follows. (55) This is known as a hormetic effect, where an initial stressor creates a compensatory response in the body—and that has positive, long-term consequences for health. (56)

9. Sleep Deprivation and Artificial Light Exposure

As more and more of us spend most of our waking hours in front of a screen, our modern lives are becoming progressively more marked by increased exposure to artificial light. That has worrying effects on our sleep. Nighttime light exposure suppresses the production of melatonin and leads to increased sleeplessness, and is linked to an increased risk of depression, even after controlling for sleep quality and chronic health conditions. (57, 58, 59, 60)

10. Standard American Diet

Research shows that the consumption of ultra-processed foods is associated with depression—and the Standard American Diet is chock-full of them. (61, 62) The Standard American Diet harms the gut microbiome and can lead to leaky gut. (63) Nutritional deficiencies are also a concern with this diet.

For a deeper dive into this topic, check out “Nutrition and Mental Health: What’s the Connection?” from nutritionist Lindsay Christensen.

Functional Medicine Treatment Options for Depression

Your diet and lifestyle habits impact every facet of your well-being, mental health included, so making adjustments in these areas is an important step if you are struggling with depression. As our understanding of the mechanisms behind depression grows, other potential treatments are coming to the forefront, as well, like bright light therapy, Eye Movement Desensitization and Reprocessing (EMDR), cognitive behavioral therapy, and even psychedelics. Building up your personal resilience can also help weather stressful situations in the future—and this is an especially useful tool for getting through the stress and uncertainty caused by the COVID-19 pandemic.

Change Your Diet

As I mentioned, a diet rich in ultra-processed foods is linked with depression; however, an anti-inflammatory, ancestral diet is associated with robust mental health. (64) An ancestral diet is also nutrient dense, making it a great option for ensuring that you get the nutrients that are beneficial for mental health, like:

  • Vitamin B6 and B12 (65)
  • Balanced zinc and copper (66)
  • Magnesium (67)
  • Omega-3 fatty acids (68)
  • Polyphenols (69)

Supplementation may offer additional benefits if you’re not able to get everything you need through diet alone. This could include:

  • 5-HTP (70)
  • Inositol (71, 72)
  • Zinc (73)
  • Magnesium (74)

An ancestral diet is also a gut-healthy diet. It’s rich in healthy fiber and free from foods that exacerbate gut conditions—and I recommend adding fermented foods for additional probiotic benefits.

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Adopt Healthy Lifestyle Interventions

Picking up healthier habits can also help alleviate your depression. That could include:

Try Other Treatment Options

Cognitive behavioral therapy is a form of talk therapy that is focused on changing patterns of thinking and behaviors that don’t support mental health. People who undergo this form of therapy learn new methods for coping, like: (75)

  • Facing their fears
  • Developing confidence
  • Learning to calm the mind
  • Using problem-solving skills to deal with tough situations

There are also several emerging treatments for depression available, like:

  • Bright light therapy: This involves daily exposure to a full-spectrum, 10,000 lux light, and has been shown to help relieve seasonal affective disorder and depression. (76)
  • EMDR: This form of therapy stimulates the two hemispheres of the brain, often through eye movements or specialized devices. Originally intended as a treatment for trauma, it’s been shown to be effective for recurrent depression. (77)
  • Psychedelics: When used in controlled, therapeutic environments, research suggests that people with depression may experience some benefit from psilocybin, LSD, or ketamine. (78, 79, 80)

Build Your Ability to Adapt in Any Circumstances

Cultivating more adaptability can be a powerful tool to use in dealing with depression. This is a crucial trait we all need to deal with uncertainty—and clearly, we need it now more than ever. We can each develop the internal and external resources needed for this, often described with the acronym “HERO.” (In positive psychology, this is known as “psychological capital.”) HERO stands for:

  • Hope
  • Efficacy
  • Resilience
  • Optimism

I recently shared a five-part plan for cultivating HERO that I hope will help you develop these resources so you can manage feelings of stress and uncertainty and learn to support your mental health.

The best thing you can do to treat your depression is to get help from a practitioner who’s trained in the Functional approach. Working with a practitioner who’s trained in a patient-centered, investigative approach can offer you the chance to address what’s really causing your depression. Find a Functional Medicine practitioner near you who can help.
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