Depression is a widespread public health problem affecting 1 in 5 adults in the US [1].
Functional medicine treatment approaches depression by exploring its root causes, rather than just managing symptoms. It is a patient-centered model of care that considers genetic, biological, and lifestyle factors that influence one’s mental health.
Functional medicine programs create personalized treatment plans for patients, focusing on strengthening the gut-brain connection, improving nutrition, and managing stress. For those with depression, approaches like ketamine therapy, neurofeedback, and TMS are also growing in popularity for quickly reducing symptoms with little side effects.
Identifying The Causes of Depression With Functional Medicine
For years, depression was thought to be caused by a lack of serotonin, a neurotransmitter in the brain. However, this theory has been oversimplified. Although serotonin plays a role in mood and low levels are associated with depression, extensive reviews confirm that there is no evidence that low serotonin is a direct cause of depression [2].
As new advances are made, functional medicine explores how key functions of the body such as nutrition, gut health, hormone cycles, and genetic predispositions influence neurotransmitters, brain activity, and overall mental well-being.
Nutritional Deficiencies and Gut Health
The gut is home to trillions of bacteria, fungi, and other microorganisms that make up the ”gut microbiome”. This ecosystem aids in digestion, nutrient absorption, and communicates directly with the brain via the gut-brain axis, a bidirectional communication network that influences key cognitive functions such as mood, sleep, appetite, and stress response.
Research has shown that dysbiosis (dysfunction of the gut-brain axis), contributes to a range of mental health challenges such as depression, anxiety, and obsessive-compulsive disorder (OCD) [3].
Nutrition plays an essential role in maintaining gut health and mental well-being. Foods that contain B and D vitamins, folate, omega 3 fatty acids, and magnesium have been shown to reduce symptoms of depression. Some research suggests the best diet for individuals with depression is a Mediterranean diet which incorporates a blend of all the necessary nutrients for good health [4].
A typical Mediterranean diet consists of the following foods:
- Fruits such as blueberries, bananas, and avocados have been shown to decrease inflammation and support brain health, such as mood.
- Vegetables such as peppers, broccoli, carrots, spinach, and sweet potato are a rich source of folate; deficiencies in this have been linked to depression.
- Whole Grains such as barley, brown rice, couscous, quinoa, are naturally rich sources of amino acid tryptophan. They are thought to support sleep and mood by aiding in serotonin and melatonin production.
- Lean protein found in chicken, tuna, eggs, greek yogurt and cottage cheese contain essential amino acids that may contribute to positive mood and improved mental clarity.
- Fermented foods popular in Mediterranean cuisine include yogurt, certain cheeses, or vegetables,. As well pickled fish, sourdough bread and kombucha are beneficial.. These introduce healthy bacteria to the gut to help balance the gut microbiome.
Hormonal Imbalances
Hormone fluctuations play a significant role in mental health and cognitive functions such as mood, emotional regulation, and stress response [5] [6].
Reproductive Hormones
These hormones are responsible for the development of sexual characteristics and play a key part in reproductive functions such as menstruation, menopause, and pregnancy.
Shifts in reproductive hormones like estrogen and progesterone affect neurotransmitters in the brain, impacting sleep, appetite, and mood. Studies have linked fluctuating estrogen levels (such as during menstruation or pregnancy) to low mood and an increased risk of depression.
Thyroid Hormones
Thyroid hormones such as cortisol, testosterone, and melatonin are growth hormones produced by the thyroid and play a key role in brain functions such as attention and hyperactivity. They also control the speed at which food moves through the digestive system, absorption of nutrients, and energy levels.
Many thyroid disorders (irregularities in thyroid hormones) are associated with symptoms of low mood and depression. Some of these include:
- Polycystic Ovarian Syndrome (PCOS) affects reproductive age women and increases their levels of androgens such as testosterone. Common symptoms include irregular periods, changes in appetite or weight gain, low mood or energy, and excessive hair growth.
- Hypothyroidism is due to an underactive thyroid gland that doesn’t produce enough hormones to meet the body’s needs. It has been linked to mood changes, including depression, and other symptoms such as fatigue, weight gain, and trouble focusing.
- Obesity has been linked to hormonal imbalances such as excess cortisol and low thyroid activity. There is a strong connection between obesity and depression, which is partially explained by hormones, nutritional deficiencies, and lifestyle factors such as lack of exercise.
Chronic Inflammation
Inflammation is the natural response to injury, infection, danger, or an outside toxin that has entered the body. It can be helpful for survival, but when it becomes chronic can trigger inflammation in the blood-brain barrier, leading to symptoms commonly associated with depression. For example, one study found that people with higher levels of C-reactive protein (a marker of inflammation) were significantly more likely to be diagnosed with major depressive disorder [7].
Other common causes of chronic inflammation include:
- Poor diet
- Lack of exercise
- Chronic stress or trauma
- Autoimmune disease
- Smoking
- Alcohol or drugs
Genetic Predispositions
According to the Journal of Frontiers in Psychiatry, approximately 37% of depression cases are attributed to genetics. In a 2025 study of over 5 million people, researchers identified 700 different genetic variations and 300 specific genes linked to depression. For example, variations in the SLC5A4 gene (which helps transport serotonin between the gut and the brain) have been linked to depression [8].
More functional medicine centers are beginning to use gene testing for personalized psychiatry to help make more informed treatment decisions for patients. Understanding genetic predispositions can help guide medication management, improving treatment outcomes and reducing the risks of adverse side effects.
What is Functional Medicine?
Functional medicine is a model of healthcare that addresses root causes of mental and physical health challenges by exploring factors such as genetics, hormones, nutrition, and gut health. It takes a personalized approach, looking at the unique needs of each patient and empowering them to have a say in the treatment process.
Functional Medicine Treatments for Depression
Functional medicine treatments for depression aim to address the underlying causes of depression previously discussed, rather than just manage symptoms. They can be particularly beneficial when paired with conventional mental health treatments, holistic approaches, and lifestyle changes.
Personalized Nutrition and Supplementation
Personalized nutrition uses dietary interventions and tailors food habits and choices to improve mental and physical health outcomes. Patients may work with a nutritionist or herbalist to find the right supplements, vitamins, or natural medicines to aid depression.
TMS
Transmagnetic Stimulation Therapy is an evidence-based treatment that regulates the nervous system to aid in mental or physical stress. It uses small magnetic pulses on the scalp to stimulate activity in regions of the brain that contribute to symptoms of depression.
A typical TMS session lasts 30 to 60 minutes and treatment courses are about 4 to 6 weeks. TMS is safe, FDA-approved, and has little side effects.
Neurofeedback
Neurofeedback training helps patients with depression observe and control brain wave frequency. Certain brain waves are associated with various cognitive functions (e.g., Delta: deep sleep, relaxation, anxiety relief). Neurofeedback treats depression by teaching the brain to self-regulate and decrease unhealthy patterns of stress that contribute to depression.
During neurofeedback therapy, small sensors are placed on the scalp to monitor blood flow in regions of the brain such as the prefrontal cortex. Besides depression, neurofeedback has also proven effective for mental health challenges such as PTSD, OCD, and ADHD.
Ketamine Therapy
In 2019, the FDA approved ketamine therapy for treatment-resistant depression. Ketamine therapy is a powerful treatment for helping patients with severe cases of depression who have already tried conventional treatments with little to no relief.
Ketamine is a dissociative anesthetic that supports the growth of new neural connections in central brain regions that play a role in emotion and mood regulation. Ketamine therapy is highly successful for treating depression, with many patients finding relief in just 1 to 2 sessions.
Functional Medicine for Depression at Maple Mental Health
Harper Clinic provides integrative functional medicine treatment to address depression, other mental health challenges, and chronic health problems. Our depression treatments include TMS, neurofeedback, ketamine therapy, and blend cutting-edge, evidence-based neuroscience with holistic whole-body approaches to address all factors of mental health.
Reach out to Harper Clinic either by phone, text, or book directly through our website to schedule your mental health consultation. Our providers can help you verify insurance benefits and set up a personalized treatment plan that meets your unique mental, physical, financial, emotional, and spiritual needs.
Sources
[1] 2023. Depressive Disorder. WHO.
[2] Browning, M. et al. (2023). Fifty years on: Serotonin and depression. Journal of psychopharmacology (Oxford, England), 37(3), 237–241.
[3] Wakefield, S. et al. (2017). Gut microbiota’s effect on mental health: The gut-brain axis. Clinics and practice, 7(4), 987.
[4] Parastouei, K. et al. (2023). The effect of Mediterranean diet instructions on depression, anxiety, stress, and anthropometric indices: A randomized, double-blind, controlled clinical trial. Preventive medicine reports, 36, 102469.
[5] Zitek, B. et al. (2008). Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability?. Journal of psychiatry & neuroscience: JPN, 33(4), 331–343.
[6] Azar, S. T. et al. (2012). The Link between Thyroid Function and Depression. Journal of thyroid research, 2012, 590648.
[7] Howes, O. D. et al. (2020). Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain, behavior, and immunity, 87, 901–909.
[8] Lane, C. 2025. Global study pinpoints genes for depression across ethnicities. University College London.
