Brain Inflammation Underlies Chronic Depression

Depression can have physical symptoms in the brain, and inflammation is one linked to chronic depression. (Shutterstock)

Traditional treatment for chronic depression typically involves medications that impact brain neurotransmitters — brain chemicals responsible for mood, motivation, behavior, and mental activity. However, many patients with depression do not respond well to pharmaceutical treatment or natural remedies such as 5-HTP or Saint John’s Wort.

While the conventional medical model insists on sticking with these minimally successful approaches, a new model of depression has emerged in recent years.

Depression, and especially chronic major depressive disorder, is typically due to what’s called the “cytokine model of depression,” or the inflammatory model of depression. Simply put, chronic brain inflammation disrupts multiple brain functions, leading to depression.

1. Brain Inflammation Slows Down Conduction Between Neurons

When the brain becomes inflamed several key things happen. First, inflammation slows down conduction between nerves. When the frequency of firing (communication between neurons) decreases in the frontal lobe and limbic lobe, this can lead to depression.

2. Brain Inflammation Impacts the Synthesis of Key Neurotransmitters

We also know brain inflammation disrupts transport carrier proteins, in particular large neutral amino acid transporter. This protein is necessary for carrying the precursors (building blocks) for dopamine and serotonin production into the brain.

Dopamine is called the “pleasure and reward” neurotransmitter. Symptoms of poor dopamine activity include:

• Inability to handle stress
• Inability to self-motivate
• Inability to start or finish tasks
• Feelings of worthlessness
• Feelings of hopelessness
• Short temper over minor upsets
• Isolating oneself from others
• Unexplained lack of concern for family and friends

Serotonin is considered the joy and well-being neurotransmitter. Symptoms of poor serotonin activity include:

• Feelings of depression
• Feelings of inner rage and anger
• Difficulty finding joy from life’s pleasures and favorite activities
• Depression when it is cloudy or when there is lack of sunlight
• Not enjoying friendships and relationships
• Not enjoying favorite foods
• Unable to fall into deep restful sleep

Inflammatory states disrupt the mechanism that allows these key precursors to cross into the brain via the blood-brain barrier, the protective layer surrounding the brain that is meant to allow good substances in and keep harmful substances out.

As dopamine levels drop, people lose their motivation and drive. As serotonin goes down, people lose their mood, sense of happiness, and satisfaction with things they used to love.

This dynamic creates a chronic pattern that may look like a neurotransmitter problem at its roots, but attempting to affect neurotransmitter levels with traditional treatments really has no effect because it does not address neuroinflammation.

3. Neuroinflammation Impacts Receptor Sites for Neurotransmitters

A third key link between neuroinflammation and depression involves the receptor sites on neurons that respond to neurotransmitters. Even in the presence of sufficient dopamine or serotonin, brain inflammation impacts the ability of these receptors to respond to neurotransmitters that bind to them. They simply can’t carry the message across the spaces between neurons.

Out of control glial cells can harm the brain

The brain is comprised of two types of cells: neurons and microglia cells. Neurons are responsible for communication within the brain. Microglia cells are the brain’s immune cells. They are in charge of facilitating healthy neuronal function, reacting to foreign invaders, and cleaning up plaque and debris.

However, unlike the immune system in the rest of the body, glial cells don’t have a well-regulated off-switch. When over-activated, glial cells create an all-out assault on antigens that enter the brain, but they don’t necessarily turn off afterward. This is what creates chronic brain inflammation that degenerates brain tissue, causing symptoms.

You can now see why so many patients don’t respond to conventional treatments that target neurotransmitter levels. When the brain is in a state of chronic inflammation, adding neurotransmitters or attempting to change how they function only covers one small part of a larger field of possible breakdowns.

I’m teaching a new course on how to identify and treat neuroinflammation, a common underlying cause of Major Depressive Disorder.

This story was originally published on the Kharrazian Institute’s Blog.