If we get a cut, the area around it becomes red, swollen, and hot. This is an example of acute inflammation, which works to heal the cut and prevent infection. This kind of inflammation is a good thing. Once the cut is healed the inflammation resolves.
Problems with inflammation start when the body remains in a state of low-level inflammation over a long period of time. This is called chronic inflammation. Current research is examining the role of inflammation in metabolic issues, cardiovascular disease, insulin resistance, obesity, diabetes, aging, and a number of brain conditions. This research suggests that inflammation may be the common pathway for many health issues.
I am increasingly recognizing the possible role of inflammation in psychiatric conditions. My patients often report a variety of inflammatory and autoimmune symptoms in addition to mental health symptoms. Times of increased emotional stress, at times come with flare-ups of pain, joint problems, skin issues, and gastrointestinal dysfunction, and other symptoms suggestive of systemic inflammation. Chronic inflammation may be the underlying mechanism that could explain both the mental health and physical health issues. Recent studies link inflammation to the following psychiatric conditions in adults and children:
Post-traumatic Stress Disorder
In addition, inflammation in children has been linked to:
Obsessive Compulsive Disorder (OCD)
Attention Deficit Hyperactivity Disorder (ADHD)
In scientific research, proving causation is much more difficult than just pointing out that two things seem to be connected. So while we cannot say with certainty that inflammation causes mental illness, research has shown that inflammation is associated with some brain disorders. How big of a role inflammation plays in brain health remains controversial and the research remains mixed.
Cytokines And The Brain
Cytokines are the key inflammatory markers involved in both acute and chronic inflammation. Cytokines are small proteins that are released in the presence of an acute injury or infection (like the cut described above). Their job is to aid in healing. However, when cytokines persist at elevated levels unrelated to any recognizable acute infection, we get chronic, low-level inflammation.
The causal link between cytokines and psychiatric symptoms is demonstrated in studies on the effects of administering interferon alpha for the treatment of Hepatitis C or other conditions. Interferon alpha is a medication meant to stimulate and mimic the human immune response resulting in inflammation. Shortly after receiving the medication patients can develop a variety of psychiatric side effects, such as confusion and lethargy. With prolonged exposure to the medication, majority of patients develop fatigue and depression. A small proportion of patients also develop irritability, hypomania or even full-blown mania. The side effects of interferon alpha treatment demonstrates that increasing the inflammatory response can cause a variety of psychiatric symptoms.
Research has shown that cytokines can cause trouble by altering hormone pathways. Take, for example, the hypothalamic-pituitary-adrenal axis, which is responsible for stress-hormone regulation and is implicated in a variety of psychiatric conditions. Stress and inflammation interact through this hormone axis in both directions. Inflammatory cytokines activate the stress hormone axis and, in turn, stress hormones affect inflammation in a complex way. Stress can both increase inflammation and also tone down inflammation through a feedback loop. When systemic inflammation consistently activates stress hormones, certain stress hormones suppress inflammation to protect from “overshoot” of the inflammatory response and the associated tissue damage. Have you noticed that sometimes you may get sick after a stressful period instead of during it? This is an example of your body protecting you from increased inflammation!
The inflammatory cytokines discussed above can have a direct, negative effect on various brain structures and functions. For example, in the adult brain, they can alter neurotransmitter supply and function and suppress neurogenesis, which is the birth of new cells.
Inflammation and Schizophrenia
The link between schizophrenia and inflammation was initially described in 1988 by researchers studying the “season of birth pattern” in schizophrenia. Researchers found that the children of mothers who were in the middle of their pregnancies during the 1957 influenza pandemic in Finland had a higher rate of schizophrenia compared to children born in other years. Later, several other studies linked various types of infections in the mothers during pregnancy to an increased risk of schizophrenia in their children. A review of these studies concluded that 30% of all schizophrenia cases could be prevented by eliminating certain prenatal infections. Since many different infections are associated with the increased risk of schizophrenia, it may be the prenatal exposure to inflammation, rather than exposure to a specific infection, that causes the trouble.
A recent study published in the American Journal of Psychiatry by Canetta et al. (September, 2014) used a database of over one million pregnancies in Finland to provide confirmation of the link between inflammation in the mother and schizophrenia in the child. Instead of looking at a specific infection, the researchers studied C-reactive protein. C-reactive protein is a marker of both acute and chronic inflammation and can be measured in the blood by a standard laboratory test. The researchers examined 777 blood samples from first or early-second trimester of pregnancy for individuals who later developed schizophrenia. The study found that very high levels of C-reactive protein in the mother during pregnancy were associated with a nearly 60% increased risk for schizophrenia in the child. The increase in risk was incremental; with a 28% increase for each unit increase of C-reactive protein. This study demonstrated that the more inflamed the mother was during her pregnancy, the higher the risk of schizophrenia was in her child.
Inflammation in Depression and Bipolar Disorder
While the above study focused on schizophrenia and the specific marker of C-reactive protein, the association between mental illness and inflammation has also been noted in other mental disorders. For example, Baumeister et al. (2014) reviewed the research studies on depression, bipolar disorder, psychosis and inflammation. This research shows links between certain cytokines and depression. The elevated levels of C-reactive protein and Il-6 precede depression. These findings support the hypothesis that inflammation may be involved in causing depression.
Studies identified elevation in a different set of inflammatory cytokines in bipolar disorder than in depression or schizophrenia. Thus different cytokines may play a role in different psychiatric conditions. Deeper understanding of the role of cytokines in mental disorders could open doors to new diagnostic approaches and treatment options.
Causes of Inflammation
The early research on inflammation focused on inflammation caused by infections. However, we are learning that inflammation can be caused by a variety of factors. As research on inflammation accumulates, the list of factors that cause inflammation continues to grow. Here are a few key examples:
Stress – Studies show that both childhood and adult stress contribute to inflammation. Childhood trauma, such as bullying, is associated with increased levels of inflammatory cytokines and may profoundly alter the activity of stress hormones. Stress increases the activation of the sympathetic nervous system; which is responsible for the “fight or flight” reaction, production of the stress hormone cortisol by the adrenal glands, and release of cytokines and other inflammatory mediators. These changes can last into adulthood.
What to do? – Research studies confirm that mind-body practices, such as yoga and meditation, are effective at lowering stress, as well as lowering stress hormones, inflammatory markers, and the “fight or flight” response
Dietary and Metabolic – Foods that cause sensitivities and irritation of the digestive tract contribute to inflammation of the intestinal lining. Poor digestion and absorption of nutrients, as well as shortage of good bacteria or overgrowth of harmful bacteria in the gut, can worsen inflammation. Research is now exploring the link between gut problems and mental illnesses, such as schizophrenia.
What to do? – Healing the gut can do much to reduce inflammation. The first step to healing the gut is improving the diet; removing harmful foods and adding beneficial foods. One useful tool for discerning which foods are harmful for you is the elimination diet. Adding probiotic foods, which support the growth of healthy bacteria, will help your body to rebalance your gut flora.
Sleep – Research shows that sleep loss increases inflammation.
What to do? – Cherish your sleep and aim for 8 hours per night.
Autoimmune conditions – In autoimmune conditions the immune system is overactive and attacks one’s own organs or tissues. Common examples are Graves’ disease, lupus, multiple sclerosis and rheumatoid arthritis. Inflammation plays a major role in the pathology of autoimmune diseases. This type of autoimmunity may play a role in a number of psychiatric conditions such as narcolepsy and schizophrenia, with inflammation as a mediator.
What to do? – Jump on the healthy lifestyle bandwagon to reduce inflammation with the suggestions above; reduce stress and optimize your gut bacteria.
Environmental Exposures – Chemicals in home products, toxins, pesticides, herbicides, cosmetics, flame retardants, dioxins, BPA and others may affect our immune systems and may contribute to inflammation. The 100,000 new chemicals released into consumer products in the last few decades are considered safe until proven unsafe. Yet Studies are now starting to document how some of these chemicals could be contributing to inflammation and disruption of the endocrine system.
What to do? – You can reduce your exposure to these chemicals by cleaning up your home and your diet, using non-toxic home products and cosmetics, and eating healthy and mostly organic food.
Prenatal Complications – There is not much we can do about the prenatal exposures that we had before our birth, yet pregnant women can do much to protect their children from inflammation. Preterm labor, preeclampsia, hypoxia, and stress in the mother during pregnancy may contribute to inflammation in the child.
What to do? – Reducing stress during pregnancy and optimal prenatal care lower the risk for prenatal complications.
Research is just beginning on the use of natural and pharmaceutical anti-inflammatory agents for the treatment of mental disorders.
Depression – A recent review of 4 studies using an anti-inflammatory drug (Celecoxib) as a treatment for depression showed good results. The group receiving anti-inflammatory medication showed higher rates of improvement than the placebo group.
Schizophrenia – A review of 8 studies on non-steroidal anti-inflammatory drugs (NSAID), such as aspirin, in patients with schizophrenia found that the NSAIDs reduced symptoms, such as hallucinations and delusions, when added to other treatments. In addition, treatment with certain serotonin receptor antagonists (5-HT3) involved in the regulation of intestinal inflammation reduced the negative symptoms of schizophrenia; such as lack of interest in the world and emotional flatness.
While these studies used anti-inflammatory medications, nature provides a wealth of natural anti-inflammatory agents. Some of the key natural approaches to reducing inflammation include:
Eating an anti-inflammatory diet
Normalizing weight and avoiding rapid weight changes
Avoiding infections and supporting the immune system by living a healthy lifestyle
Avoiding chemicals, pesticides and environmental toxins
Inflammation may be the common pathway for the development of disorders as diverse as back pain and depression. We are just beginning to understand how preventing, reducing and treating inflammation may protect us from psychiatric and neurological conditions. There is a lot that we can do to reduce chronic inflammation and improve health through the healthy lifestyle changes discussed above.