Inflammation and depression are linked — but what keeps the immune system inflamed?
STUDY: Bindroo A et al, Brain, Behavior, and Immunity 2026; doi:10.1016/j.bbi.2026.106577
STUDY TYPE: Review
FUNDING: National Institute of Mental Health; National Institute of General Medical Sciences
Background
Inflammation is a normal immune response. It is supposed to be short-lived, but when it goes on too long it can cause depression. It wears down dopamine, causing low motivation and anhedonia. Around 24% of depressed patients have low-grade inflammation compared to 16% of controls. For treatment-resistant depression, the rate is 50%.
Why Inflammation Persists
Several factors can turn inflammation chronic, and most of them have to do with changes in modern life:
- Insomnia: Sleep restores immune function, and insomnia amplifies inflammation, as do disruptions of circadian rhythms such as light at night. A therapy for insomnia (CBT-i) reduces depression and inflammation.
- Stress: Early-life stress and trauma primes the immune system toward a more reactive, less self-resolving state, while ongoing stress activates inflammatory pathways through the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis (ie, stress hormones like cortisol)
- Sedentary living and energy-dense, ultra-processed foods cause inflammation
- Obesity: As fat cells grow, they outstrip their blood supply and die, leaving necrotic material that triggers an immune response
- Sanitation: As we take more antibiotics and spend less time in nature, we lose contact with microbes that regulated the immune response, including changes in the gut microbiome
- Infections: Viruses and other infections trigger chronic inflammatory responses that worsen mood and cognition, including like COVID, HIV, and HSV
Many of these are inter-linked. Stress worsens sleep, and insomnia worsens obesity and metabolic health, all of which raise the risk of infections.
Gender: Depression is three times more common in women, and inflammation may be part of the reason, as women have stronger immune responses than men on average.
Genetic factors are also involved. Genes that protect infants from infections by activating immunity may trigger over-reactive inflammation in later life.
Practice Implications
- I’ve highlighted links to lifestyle interventions above that treat depression and address causes of inflammation
- These are not “lightweight” interventions for mild depression. Some studies suggest they are more effective in more severe cases, and address the inflammatory pathways that keep antidepressants from working
- Learn more about the anti-inflammatory approach in Difficult to Treat Depression
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- Are you checking for inflammation in practice with an hs-CRP?
- Which approaches do you find more effective for patients with inflammation?
One comment
Chris Cotner
April 9, 2026 at 9:56 am
This is all very important and practical information for all clinicians treating depression. Thank you Chris for your ongoing contribution to making the practice of psychiatry the best that it can be by looking at multifactoral approaches to address patient care. Yes, I often check a hs-CRP. Regarding lifestyle factors, I often take the “Atomic Habits” principles approach to help patients start working towards living a better life. If people are sedentary with no daily rhythm and eating primarily ultra processed foods, I like to create a program with them to take the next best step in a away that is agreeable and sustainable to them, so that they will reach their goal of truly making behavioral changes in their way of living. I want to partner with them, not blame them, or make them feel like their depression is all their own fault. I also do not want to heap up a dozen New Year’s resolutions on them all at once. They’ll just feel overwhelmed and defeated when perhaps just getting out of bed is already a challenge. Perhaps start with a regular bedtime, eat a quality protein source for breakfast, add a serving of fruit or vegetables to their day, and go for a 10 minute stroll outside each day, and routinely build on that. I often start by encouraging our adding a good thing to their lifestyle other than over talk about what needs to go and they need to stop, like maybe their drinking 4-6 sodas per day and have been for the last ten years. We will get to that and it’s important. Get good momentum going first with awareness and empowerment and lots of great things can happen. Thank you for the opportunity to share.