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If your antidepressants aren’t helping your severe depression or suicidal thoughts, you’re not alone — but an alternative could be the key. New research shows brain inflammation plays a key role in depression, pointing the way to new treatments for depression and suicidal ideation.

For decades, depression has been treated as a chemical imbalance in the brain’s neurotransmitters — most often serotonin, norepinephrine, and dopamine.

Commonly prescribed medications such as SSRIs (selective serotonin reuptake inhibitors) and NDRIs (norepinephrine and dopamine reuptake inhibitors), attempt to resolve depression by changing how the brain stores, transports, and reabsorbs these key brain chemicals.

While this treatment helps some, it proves inadequate for many others. For those with severe depression and suicidal thoughts it can strand them in the danger zone with nowhere to turn.

The inflammatory model of depression: Microglial over-activation

New research reveals the root of depression may not be chemical imbalance but instead chronic inflammation that disrupts brain function. This can lead to malfunctions in how the brain manages not only its neurotransmitters, but other key functions such as fighting inflammation, immune response, and communication with the rest of the body, including the gut.

A team at the University of Manchester has found a strong correlation between major depressive episodes and increased neuroinflammation — inflammation of the brain’s neurons.

At the root of this relationship is increased activity of microglia cells (glial cells), the immune cells of the brain and nervous system.

Glial cells outnumber other neurons in the brain and are responsible for removing debris from the brain. As neurons die, the glial cells chew off the dead portions so that communication between remaining cells is not impaired.

Under normal circumstances, glial cells do their cleanup and the brain returns to normal. However, processed foods, environmental toxins, sleep deprivation, and chronic stress spikes inflammation in the brain.

Unlike other immune cells in the body, glial cells don’t have an easy off-switch. When brain inflammation continues unabated, glial cells become over activated, creating an inflammatory cascade that damages neighboring neurons and destroys their ability to communicate with each other. This can result in brain fog, depression, and worse.

Glial cell over activation is fueled by:

• Chronic systemic inflammation
• A diet high in sugars, carbs, processed foods, and industrial seed oils
• Poorly regulated blood sugar
• Food sensitivities
• Autoimmunity and other chronic health conditions
• Chronic viral infections
• Traumatic brain injuries (even minor concussions)
• Gluten sensitivity

Glial cell over activation linked to suicidal thoughts

The study compared subjects with moderate to severe depression and suicidal thoughts to a control group of healthy subjects with no depression. In the depressed group, brain scans showed increased microglial activity.

The most significant increase was observed in the part of the brain responsible for mood regulation, pointing to a link between suicidal thoughts and increased brain inflammation. The control group showed no elevated glial activity.

Prior studies of post-mortem suicide subjects also showed similar inflammation in these brain regions.

Do I have glial cell over activation?

Look for these clues your brain is inflamed:

• Brain fog
• Depression
• Anxiety
• Poor memory
• Physical or mental fatigue
• Difficulty finding words
• Gut inflammation (the gut is connected to the brain via the vagus nerve)
• Food sensitivities
• Leaky gut

Lowering brain inflammation to relieve depression and suicidality

Many functional neurology patients have relieved depression by addressing brain inflammation.

Below are ways you can minimize inflammation and protect your brain.

Exercise regularly. Exercise can literally save your brain. Raising your heart rate a few times a week positively impacts your brain by flooding it with healthy brain compounds such as brain derived neurotrophic factor (BDNF), which helps neurons communicate better. It only requires a few minutes of high intensity exercise to increase BDNF levels. The more coordination required for the exercise, the better it is for your brain.

Control blood sugar. Whether you have chronic high blood sugar (insulin resistance) or low blood sugar (hypoglycemia), imbalanced blood sugar is inflammatory to the brain. Left unmanaged, it can be one of the most damaging factors for the brain. In fact, chronic high blood sugar is so damaging to the brain, neurologists call Alzheimer’s disease “Type 3 diabetes.”

Symptoms of chronic high blood sugar (insulin resistance):

• Constant sugar cravings, especially after meals
• Fatigue after meals
• Constant hunger
• Waist girth equal to or larger than hip girth
• Frequent urination
• Increased appetite and thirst
• Difficulty losing weight
• General fatigue

Symptoms of chronic low blood sugar (hypoglycemia):

• Lack of appetite or nausea in the morning
• Sugar cravings
• Eating to relieve fatigue
• Irritability, light-headedness, or dizziness when you miss a meal
• The need for caffeine for energy
• Energy crashes in the afternoon

Adopt an anti-inflammatory diet. American diets are high in sugars, processed foods, allergens such as corn, soy, and wheat, and inflammatory foods such as gluten and nightshades. An anti-inflammatory elimination and reintroduction diet can help determine what foods may be causing you undue inflammation. Contact my office for guidance on how to manage this protocol.

Fix leaky gut and leaky brain. Leaky gut happens when the lining of the small intestine becomes inflamed, damaged, and over-porous, allowing undigested food particles, toxins, and other pathogens into the bloodstream. These pathogens trigger an immune cascade that leads to systemic inflammation, increasing your risk for more inflammation, food sensitivities, and autoimmune disease.

The brain is surrounded by a protective layer called the blood-brain barrier (BBB), meant to allow nutrients in and keep pathogens out. Similar to leaky gut, inflammation can disrupt the integrity of the BBB, making it over-permeable.

This allows inflammatory pathogens into the brain, firing up the immune response and glial over activation. Once the BBB is leaky, many other immune triggers can feed the inflammatory fire.

Avoid gluten. Gluten exposure opens the lining of the blood-brain barrier, allowing inflammatory pathogens into the brain and contributing to glial over activation and damage to brain cells and function.

For those with celiac disease, gluten exposure activates zonulin, which opens the lining of both the gut and the BBB, leading to more brain inflammation.

Manage stress. Regular stress-reduction practices are anti-inflammatory and provide great benefits for brain health. Even a few minutes a day of one of the following can make a difference:

• Meditation
• Deep breathing
• Yoga
• Tai Chi
• Dance
• Laughter
• Hug a tree
• Walk in nature
• Gratitude journaling

Improve circulation to the brain. In addition to exercise, look for other ways to increase brain circulation such as:

• Gingko biloba
• Eliminate smoking
• Address asthma
• Address hypothyroidism (and associated anemia)

Address head injuries. If you have a head injury, you need to address it no matter how mild or severe. Even a mild head injury can initiate glial cell-over activation, and many with old untreated head injuries have an inflammatory fire smoldering in the brain that can erupt years later in the form of mood issues, brain dysfunction, and worse. Those with multiple head impacts over time are especially at risk — even if the injuries have all been minor.

While it was previously thought that the intensity of the head trauma mattered most, we now know that other factors such as an inflammatory diet, lack of exercise, toxic overload, and chronic stress set the stage for how well your brain and immune system will respond to trauma, regardless of the intensity.

An exciting future for depression treatment

Ongoing research will offer more answers to how inflammation relates to depression. Meanwhile, functional neurology offers numerous tools to reduce its impacts on the body and brain. For more guidance into how you can use the above tools to minimize brain inflammation and reduce your depression, contact my office.