There is growing interest in the role of the brain’s immune system in psychiatric disorders – in particular, the microglial cells. Several studies have shown that some patients with psychiatric disorders have increased microglia activity but the implications are still unclear.
The disease processes involved in psychiatric illnesses are not well-understood. The possibility that the brain’s immune system might play a role was first considered over 100 years ago. In recent decades, new techniques for investigating the brain have allowed researchers to explore different theories in more detail. In particular there is growing interest in microglial cells – immune cells found in the brain which are activated when there is tissue damage or infection. Microglial cells are also involved in brain development.
Researchers at King’s College London performed an extensive review of recent studies on microglial activation in psychiatric illnesses to see if any patterns are emerging. They recently reported their findings in the Lancet Psychiatry journal. They reviewed post-mortem studies and clinical studies using brain scans from patients with psychiatric illnesses. They also looked at experimental animal studies.
In postmortem studies on brains of patients with schizophrenia, some showed increased microglial activity, some decreased activity and some no difference compared with those unaffected by psychiatric disorders. The researchers suggested that these inconsistent results could be due to different study designs, such as examining different parts of the brain, or including patients with differing degrees of illness. Other postmortem studies have considered the effects of death by suicide. Patients with depression or other psychiatric illnesses who died by suicide show a significant association with increased microglial activity.
Microglial activation in living patients can be tested using PET brain scans with selective radioactive markers for microglial cells. Several studies have looked at a range of psychiatric conditions by comparing brain PET scans of patients with schizophrenia, depression and psychosis with those of healthy people. The results have been inconsistent, with some PET scans indicating increased microglial activity in psychiatric illness and others showing no difference from healthy people.
MRI scans are another method of brain imaging which can be helpful in looking at changes in the brain during psychiatric illness. Although MRI scanning cannot show microglial cell activity directly, it can detect signs of neuroinflammation. MRIs are widely available, relatively cheap and do not use of radioactive particles, making them a safer and more economical option for repeated scanning. So far, MRI studies have reported conflicting findings. However, there is hope that ongoing development of new MRI techniques will be helpful in the future.
Due to many influencing factors, it is difficult to get a clear picture of the pattern of neuroinflammation in psychiatric illness. Although they also have limitations, animal experimental models can be helpful as they allow invasive techniques to examine the brain changes seen with specific risk factors. Several rodent studies have looked at the effects of environmental stress on the brain. The results show that stress causes increased microglial activity. Other factors which might be related to psychiatric disorders, such as repeated exposure to harmful substances or infectious pathogens, also cause microglial activation. However, the implications of these brain changes are still unclear. They may be a harmful or beneficial body reaction, or even just incidental findings.
With growing interest in the links between microglial cell activation and psychiatric illnesses, research has been focused on whether microglia could be a target for treatment. One drug proposed to have an effect on microglial activity is minocycline, an antibiotic drug which also has anti-inflammatory actions. Several animal studies have shown that minocycline can reduce the microglial activation induced by chronic stress. Clinical trials of minocycline in patients with schizophrenia or depression have had inconsistent results. This could be due to poor selection of patients – since microglial activation is only present in some patients with psychiatric illness. Some trials testing anti-inflammatory treatments in depression have shown that they are only effective in patients with increased inflammation.
There is increasing evidence suggesting that there is activation of microglial cells in a subset of patients with a range of psychiatric illnesses. The cause and implications of these changes in the brain are unclear. Some post-mortem studies have shown that increased microglial activation is associated with suicide rather than a specific psychiatric illness. The researchers suggest that microglial activation could be an indication of more severe illnesses which are difficult to treat. It is essential that we further our understanding of the disease processes in psychiatric illness, as this will offer opportunities to develop new treatments.
Written By: Julie McShane