When we are exposed to an infection, for example influenza or a stomach bug, our immune system fights back to control and remove the infection. During this process, immune cells flood the blood stream with proteins such as interleukin-6 (IL-6), a tell-tale marker of infection.
However, even when we are healthy, our bodies carry trace levels of these proteins – known as ‘inflammatory markers’ – which rise exponentially in response to infection.
A study published in JAMA Psychiatry today has shown for the first time that children with high everyday levels of these proteins in their blood are at greater risk of developing depression and psychosis in early adulthood.
A team of scientists from the department of psychiatry led the longitudinal study, which looked at a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children, taking blood samples at age 9 and following up at age 18 to see if they had experienced episodes of depression or psychosis. The team divided the individuals into three groups, depending on whether their everyday levels of IL-6 were low, medium or high.
They found that those children in the ‘high’ group were nearly two times more likely to have experienced depression or psychosis than those in the ‘low’ group. Dr Golam Khandaker from the BCNI led the study. He commented that: “Our immune system acts like a thermostat, turned down low most of the time, but cranked up when we have an infection. In some people, the thermostat is always set slightly higher, behaving as if they have a persistent low level infection – these people appear to be at a higher risk of developing depression and psychosis. It’s too early to say whether this association is causal, and we are carrying out additional studies to examine this association further.”
The research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. People with depression and schizophrenia are known to have a much higher risk of developing heart disease and diabetes, and elevated levels of IL-6 have previously been shown to increase the risk of heart disease and type 2 diabetes.
Professor Peter Jones, Head of the Department of Psychiatry and senior author of the study added: “Inflammation may be a common mechanism that influences both our physical and mental health. It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.” Low birth weight, a marker of impaired foetal development, is also associated with increased everyday levels of inflammatory markers as well as greater risks of heart disease, diabetes, depression and schizophrenia in adults.
This potential common mechanism could help explain why physical exercise and diet, classic ways of reducing risk of heart disease, are also thought to improve mood and help depression. The group is now planning additional studies to confirm whether inflammation is a common link between chronic physical and mental illness. The research also hints that illnesses like depression could potentially be treated with anti-inflammatory drugs, such as aspirin. Previous research has suggested that aspirin used in conjunction with antipsychotic treatments may be more effective than just the antipsychotics themselves.
A multicentre trial is currently underway into whether the antibiotic minocycline, used for the treatment of acne, can be used to treat lack of enjoyment (known as anhedonia), social withdrawal, apathy and other so called negative symptoms in schizophrenia. Minocycline is able to penetrate the ‘blood-brain barrier’, a highly selective permeability barrier which protects the central nervous system from potentially harmful substances circulating in our blood.
The ‘blood-brain barrier’ is also at the centre of a potential puzzle raised by today’s research, as many inflammatory markers and antibodies cannot cross this barrier, which raises questions about how immune responses can have an effect on the brain. Studies in mice suggest that the vagus nerve, which connects the brain to the abdomen, may be involved. When activated by inflammatory markers in the gut it sends a signal to the brain, where immune cells produce proteins such as IL-6, leading to decreased levels of the ‘happiness hormone’ serotonin. Similarly, the signals trigger an increase in toxic chemicals such as nitric oxide and kynurenic acid, which are bad for the functioning of nerve cells.
The research was mainly funded by the Wellcome Trust, with further support from the National Institute for Health Research and the Medical Research Council. This article was adapted from a University of Cambridge press release. New study sheds light on links between the immune system and mental illness. August 14, 2014
