Inflammation Causes Anxiety: Root Cause and Cure

What causes anxiety? Hello! Ah! I'm Anxiety. Obviously, the answer is many things. But an underappreciated truth is that behavior states and emotions, including anxiety, can be the consequence of a metabolic state. Brand new data show how inflammation, activation of the immune system, and certain signaling molecules can act directly in the brain to promote or soothe anxiety. Now, this one is somewhat personal for me. I spent years suffering from inflammatory bowel disease, ulcerative colitis, and it was catastrophic for my mental health. It certainly caused anxiety. But broadening beyond my own experience, doctors have long observed a curious phenomenon. After certain inflammatory infections or flare-ups of autoimmune diseases, like ulcerative colitis. Some people experience mood swings and anxiety even after the infection or the flare resolves. There's a prolonged effect on mood and anxiety. And these new data shine a light on both my personal experience and that phenomenon. They argue that inflammation doesn't just make you feel physically sick. It can have direct actions on the brain to cause anxiety. Now, let me show you with data. The story of the study begins with its antagonist, its villain, the inflammatory molecule called interleukin-17, or IL-17 for short. Now, to be clear, inflammatory molecules like IL-17 aren't just bad exactly. I'm simplifying here. Inflammation is part of the immune response and has its functions. But in this story, and in the modern world in general, IL-17 is the culprit. IL-17 levels are increased in inflammatory disorders like psoriasis, inflammatory bowel diseases, ulcerative colitis and Crohn's disease, rheumatoid arthritis, and ankylosing spondylitis, among others. IL-17 levels and elevated IL-17 levels in inflammatory diseases are certainly relevant to humans, maybe you or a loved one you know. But to prove a causal connection between IL-17 and anxieties, researchers turned to animal models in which they can do experiments. Researchers treated mice with a chemical that increases IL-17 levels, and this made the mice more anxious on 3 different validated behavioral tests as compared to control animals. And next, to connect the dots, the researchers looked for IL-17 receptors in the brain. Indeed, they found that IL-17 receptors were concentrated in the anxiety center of the brain, the basolateral amygdala. And they found that directly administering IL-17 into the brain induced anxiety. Furthermore, chemically turning on or off these neurons, like a light switch, in the basolateral amygdala, the neurons that harbored these IL-17 receptors, this turned on or off anxiety in the animals, respectively. Pretty cool. And this strongly suggests that neurons in the basolateral amygdala of the brain can cause anxiety, and that increasing levels of the inflammatory signaling molecule IL-17 activates these basolateral amygdala neurons to promote anxiety. Now, to delve one level deeper on how this works, in a subsequent experiment, the researchers showed that IL-17 makes these neurons in the basolateral amygdala more excitable. Basically, IL-17 makes these neurons more prone to fire. Neurons communicate with each other by firing off things called action potentials. And IL-17 made the neurons fire and fire more rapidly. You can see that here in Figure 5B from the paper. The spikes you see represent voltage traces from neurons given different levels of current. And there's clearly more activity, more neuron firing in the IL-17-treated neurons as compared to controls. In a way, it's analogous to the human behavioral state of anxiety. Because if you're feeling more anxious and someone says, taps you on the shoulder, you're more excitable, more likely to jump. It's similar with your neurons, and IL-17 is one chemical making that happen. But there's also a counterbalance, an anti-inflammatory molecule called interleukin-10, or IL-10. Whereas IL-17 increases inflammation, IL-10 reduces inflammation, it reduces excitability of neurons in the basolateral amygdala, and it appears to reduce anxiety as well. So in summary, stepping back, looking at the big picture, inflammatory molecules, IL-17, and anti-inflammatory molecules, IL-10, signal as neurotransmitters in the brain. They bind to receptors in the anxiety center, tuning anxiety up inflammation, or down, anti-inflammation. This has real-life practical consequences. It implies that altering levels of these inflammatory and anti-inflammatory molecules through lifestyle or through innovative future medications, we could directly influence brain activity and mood states. Let me give you some examples from the literature. Data suggests that westernized diets rich in sugar and processed foods associate with increased IL-17 levels. Now, obviously, a westernized diet is complex. There's a lot that goes along with it. But the point is that living this way, this westernized lifestyle, can have a direct and material impact on anxiety and mental health. So that so-called Happy Meal might actually be an anxiety meal in disguise. Ba-da-ba-ba-ba! I'm having an anxiety attack. And even electrolytes may impact IL-17 levels. In one study, potassium supplementation against the backdrop of a high sodium diet was linked to reduced IL-17 levels. So electrolyte balance could influence IL-17 and therefore influence anxiety. And in another study, pigs supplemented with beta-glucans from certain seaweeds were also found to have reduced IL-17 levels. Kind of interesting, right? And maybe an excuse to go get sushi tomorrow. Anyway, what does all this mean? It means anxiety is not just in your head, it's in your body too. Your immune system and your brain are in constant conversation. Inflammatory molecules like IL-17 can dial your brain into a hyper-anxious state, whereas anti-inflammatory molecules like IL-10 can calm it back down. And the choices we make every day—what we eat, how we move, How we sleep— my sleep's kind of crappy, maybe that's why I have anxiety— how we manage stress— I don't meditate that much, but I probably should— they all feed into the inflammatory balance. And you've now seen what I've identified for my areas of improvement. Anyway, this doesn't just mean inflammation is the only cause of anxiety, but it is a powerful, underappreciated lever that we can pull to influence our mental health. For me, this new paper, this learning, was empowering. It gave me a new lens through which to view my own struggles, not as a personal failure, but as a physiologic response to inflammation. And for all of us, it opens doors to new strategies for healing. Yes, there is a role for therapy and medication. I'm not saying there's not. But there's also a role, a big role, for food, for sleep, for gut health, for lifestyle, for treating the body to treat the mind. Because at the end of the day, mental health is metabolic health, and metabolic health is mental health. And by tending to both, we can begin to turn the tide on anxiety, not just with willpower, but with metabolic wisdom. Now, if you found this video interesting and empowering, please say thank you by hitting the like button and subscribing. These aren't just vanity metrics for my ego, but help get this information to more people. So do like IL-17 does to anxiety and dial up the reach on these data. Stay curious and stay calm.