Inflammation – Medicine’s new frontier – Could explain everything from dementia to depression

Inflammation has traditionally been thought to be a good thing. It helps fight infections and heal wounds. But, more and more, scientists and doctors are finding that inflammation has a dark side. It may be involved in many, if not all, disease processes. In recent decades, many successful breakthroughs and new therapies have been treatments that target immune and inflammatory causes of disease. Examples include new treatments for autoimmune diseases and rheumatoid arthritis in the 1990s and cancer immunotherapy in the 2010s. Researchers now believe that low-grade inflammation (which can only be detected on blood tests) may be responsible for many public health problems such as stress and obesity. One of the emerging areas of research is brain inflammation. Doctors were traditionally taught that an impenetrable barrier separates the brain from the immune system. However, 21st-century research has shown that the two are intimately connected and that inflammation can deeply impact the brain. This new understanding has led to advances in multiple sclerosis (MS) treatments. Many new MS drugs are designed to protect the brain from damage by the patient’s own immune system. The hope is that this can be extended to other mental health conditions. Controlling brain inflammation could potentially lead to new therapies for conditions such as dementia, depression, and psychosis. Interestingly, a drug that was originally developed to treat MS, natalizumab, is being tested as a possible treatment for schizophrenia. How realistic is the hope that controlling inflammation can help people with depression? There is no reasonable doubt that the two are interconnected. However, the important factor is causation, not merely correlation. In other words, scientists are trying to answer the question: Does brain inflammation cause depression? And if this is true, then how? One experiment involved imaging the brain with a functional MRI scan before and after a provoked inflammatory reaction with a typhoid vaccine. The results showed that brain inflammation caused by the vaccine was associated with a deterioration in mood. A meta-analysis that examined more than a dozen versions of this experiment confirmed that inflammation affects brain activity. Interestingly, the effects of inflammation were localized to areas of the brain known to be involved in many psychiatric disorders, including depression. The question is if inflammation causes depression, then anti-inflammatory medications should have antidepressant effects. Several studies have shown that patients with arthritis, which is often associated with depression, have significant improvement in mental health after treatment with anti-inflammatory medications (compared to patients treated with a placebo). However, most large studies have focused on physical effects of anti-inflammatory drugs, so it is difficult to assess the mental effects. Why don’t scientists design studies which specifically test anti-inflammatory drugs for antidepressant effects? The problem is that depression is not a specific diagnosis. There is no one blockbuster drug that can make the world a happier place. Psychiatric treatment needs to be personalized. Using blood tests to assess inflammation levels could be one of the choices we make in the future to prescribe customized depression treatments. A Wellcome Trust funded consortium is testing a new anti-inflammatory drug for effects on depression. This is one of the first trials that will use blood tests to screen participants for inflammation. Only people who show evidence of inflammation will be recruited into the study. The premise is that only people who have inflammation can potentially benefit from the anti-inflammatory treatment. Another example is ketamine, a prescription general anesthetic that has become a popular drug of abuse for its hallucinogenic effects. Ketamine does not work equally well in everyone. It’s mechanism of action is through blocking glutamate receptors in the brain. Interestingly, inflammation is known to increase glutamate in the brain. It is possible that people with inflammation and higher glutamate levels are more responsive to ketamine than non-inflamed individuals. In the future, scientists may be able to develop biomarkers that identify inflammation and predict which people with depression could benefit from ketamine. The scope of these anti-inflammatory medications extends beyond depression. Biotech researchers are testing anti-inflammatory drugs for debilitating neurological conditions such as Parkinson’s and Alzheimer’s. There is also potential for treating conditions such as stress, obesity, and gut and gum diseases that may be associated with low-grade inflammation and could benefit from anti-inflammatory drugs. Dozens of studies are assessing the effects of non-drug interventions, such as meditation, mindfulness, and lifestyle modifications, on inflammatory conditions. Perhaps the most interesting is a trial that is looking at whether low-grade inflammation is associated with rapid age-related cognitive impairment and whether cleaner teeth can control periodontitis (gum inflammation) and protect against senility. The results are not yet out but who would have imagined that a brighter smile could be directly related to better short-term memory and that both are potentially attainable with a toothbrush. The research on inflammation has given the scientific community a new perspective on the relationship between the body and mind. This will influence how healthcare systems are designed to deliver physical and mental healthcare in the future. Currently, the two are sharply separated. There is a prejudice against viewing the body and mind as deeply interconnected, even though many patients recognize the links in their own experiences with illness. Inflammation – medicine’s new frontier – may be the thing that clearly aligns the two, transforming scientific thinking and breaking down barriers between mind and body in clinical practice.