Inflammation, periodontitis and depression
Sarah Gingell and Nadir Khan explain how periodontitis could be linked to our mental health and how dental professionals could help with mental health care.
Periodontitis is one of the most common inflammatory disorders, affecting approximately half of adults worldwide. Its link with systemic conditions such as heart disease or diabetes is well-known.
Less well-known is that generalised inflammation is also a potent risk factor for mental health conditions such as depression and anxiety; and conversely, that the likelihood and severity of gum disease can be affected by mental health status.
Periodontitis is a chronic, multifactorial, inflammatory disease. In the early stage of gingivitis, plaque bacteria irritate the gums triggering a local inflammation, and the gums bleed easily on tooth-brushing. Local inflammation is a normal, defensive immune response to injury and infection, that under healthy conditions and with removal of plaque leads to resolution through natural pathways of healing. Blood flow is increased to a region, the permeability of local capillaries is increased to allow an easier exchange of fluids and proteins between damaged cells and blood, and white blood cells are released to attack invading microorganisms.
If left untreated, gingivitis can progress to periodontitis. If the microbial species continue to grow and cannot be eliminated, or the immune response itself is defective and sustained, certain bacteria and toxic by-products from both the bacteria and immune enzymes start to break down gum tissue, bone and connective tissue. With time, teeth are no longer securely anchored in place and may be lost.
Periodontitis is associated with raised markers for inflammation throughout the body, such as the pro-inflammatory cytokines TNF-alpha, IL-6 and IL-1beta, CRP (a measure of inflammation) and gamma-glutamyltransferase (a marker of oxidative stress).
Possible mechanisms by which periodontitis might affect distant organs include the direct migration and colonisation of bacterial species to distant areas resulting in a local inflammatory immune response in the new region; and the transmission of inflammatory agents from the oral site. Chronically raised systemic pro-inflammatory cytokines, and the systemic dissemination of periodontal bacterial products, underpin the well known link between periodontitis and heart disease and diabetes.
Periodontal disease links
Increasing evidence suggests that periodontal disease-related inflammation can also be linked to rheumatoid arthritis, some cancers, premature birth and dementia. Whilst the link between mental illness and poor dental health has been long established, it has usually been understood as resulting from the poor self-care and lifestyle often observed in those with poor mental health.
Typically the finger has been pointed at factors such as negligent oral health care, poor diet, smoking and alcohol use. Stress can also reduce saliva volume and affect its composition, which can also contribute to poorer dental health.
In the other direction, any causal effect of poor oral health on mental health has been presumed to be psychological, namely that dental problems can lead to self-consciousness or negative ruminations on health or mortality, which in turn affect psychosocial functioning and mood. However, recent research shows that chronic systemic inflammation directly affects neural systems and behaviour in very specific ways, which suggests that the dental/mental health link is likely to be physiological as well as psychosocial. Increased peripheral cytokines directly affect the brain systems that are known to be involved in depression (such as the hypothalamus, hippocampus and prefrontal cortex), and reduces levels of serotonin, dopamine and norepinephrine in the brain, changes often correlated with mental illness.
Furthermore, inflammation reduces the production of brain-derived neurotrophic factor BDNF, which is central to the creation of new neurons and synaptic connections. Experimentally, the administration of inflammatory agents leads directly to ‘depressive behaviour’ such as social withdrawal, reduced motivation and motor activity, and increased anxiety. Such behaviour is also correlated with natural levels of inflammatory markers in human individuals.
A short-term ‘sickness behaviour’ in response to inflammation that tends to make us lay low and conserve energy when we are injured or fighting an infection makes sense from an evolutionary point of view. However, it is easy to see how chronic inflammation could underpin mental health disturbances if it causes long-term effects on systems that signal reward, mediate threat and responses to it, or affect motivation.
It is important to note that not all people with clinical levels of depression show high inflammation, and conversely, that not all people with inflammation are depressed. Thus systemic inflammation should be seen as one trigger for depression, amongst others.
A resilient person who has few other risk factors for depression may cope with the additional ‘load’ of systemic inflammation without succumbing to depression, whereas someone with several other psychological or inflammatory risk factors may not.
Implications of a link
The idea that immunological processes may play a pivotal role in the development of psychiatric conditions and their treatment is a fascinating area of current research. It is now clear that generalised inflammation is a potent risk factor for depression and stress-mediated changes in behaviour. However, whilst periodontitis causes systemic inflammation, and various clinical studies do imply a causal link between periodontitis and depression, the idea that periodontitis is a risk factor for depression is not definitively proven at present and studies are ongoing.
Clinical implications of a link between periodontitis and depression:
- The importance of oral health should be emphasised in those with poor mental health.Effective treatment of periodontal disease reduces systemic inflammatory load, which may support recovery from mental illness.The effective treatment of periodontitis in those under stress (for example, a recent bereavement) might reduce susceptibility to mental illness and improve psychological well-being
- A consideration of mental health issues might be warranted when there is a poor response to periodontal interventions, or a sudden unexplained increase in oral destruction.Psychological stress is one of the most potent triggers for inflammation. Through a complex cascade, the release of epinephrine and norepinephrine leads to upregulation of proinflammatory cytokines. Stress has been directly linked to the progression of periodontitis.Chronic conditions such as depression and anxiety are also associated with physiological changes that may directly hasten the progression of periodontal disease.One of the most common side effects of psychotropic drugs is xerostomia (dry mouth). Medication can change both the volume and make-up of saliva reducing its protective function, and allowing oral bacteria levels to skyrocket.
Whilst dental professionals cannot be expected to provide mental health care, it is worth noting how much a friendly, concerned word can mean to someone. The UK – like much of the developed world – is facing a mental health crisis. People in their teens and twenties in the UK have the second worst mental well-being in the world, whilst more than 40% of menopausal women experience at least some signs of depression, and suicide is the biggest killer of men under 45.
Many people are reluctant to trouble their doctor with mental health concerns, but may have ongoing routine appointments booked with a dentist. Asking regular patients about recent stresses, or how they’ve been can be a manageable way to raise the issue.
‘My dentist said…’ might be just the words your patient needs to open a much-needed conversation about their mental health with their doctor.