Abnormalities in the brain’s immune cells cause major depression, according to a discovery at the Hebrew University of Jerusalem whose researchers think it could revolutionize next-generation medical treatment for psychiatric patients.Drugs that restore the normal functioning of these cells can be effective as fast-acting anti-depressants, the researchers said.“Microglia” cells in the brain, acting as the first and main form of active immune defense of the central nervous system, may be a key to causing depression, said psychobiology Prof. Raz Yirmiya, director of the HU psychoneuroimmunology lab. He has just published what has been described as a “groundbreaking theoretical review paper” in the peer-reviewed journal, Trends in Neurosciences.Microglia, which comprise 10 percent of all brain cells, are the brain’s immune cells that fight bacterial and viral infections. They also promote repairing and healing processes of damages caused by brain injury and trauma.“Our views on microglia have dramatically changed over the last decade,” he said. “We now know that these cells play a role in the formation and fine-tuning of the connections between neurons (synapses) during brain development, as well as in changes of these connections throughout life. These roles are important for normal brain and behavioral functions, including pain, mood and cognitive abilities.”Major depression, which afflicts one in six people at some point in their life, is the leading global cause of disability – surpassing cardiovascular and respiratory diseases, cancer and HIV/AIDS combined.“Progress in the understanding of the biology of depression has been slow,” said Yirmiya, and it requires expanding our knowledge beyond the “abnormalities in the functioning of neurons.” Other brain cells – often neglected by researchers – may be more relevant in causing depression, he said.Some forms of depression may result from malfunctioning microglia, he said, but this does not mean that all sub-types of depression or other psychiatric diseases are caused by abnormalities in these cells.Yirmiya’s new research could have a profound impact on the future development of anti-depressant medications; current drugs do not always have the desired effect on patients, so there is an urgent need to discover novel biological mechanisms and drug targets for diagnosing the root cause of depression and for treating such patients appropriately.“Studies in humans, using postmortem brain tissue or special imaging techniques, as well as studies in animal models of depression, demonstrated that when the structure and function of microglia change, these cells can no longer regulate normal brain and behavior processes and this can lead to depression,” Yirmiya said.Indeed, changes in microglia occur during many conditions associated with high incidence of depression, including infection, injury, trauma, aging, autoimmune diseases such as multiple sclerosis and neurodegenerative diseases such as Alzheimer’s.In these conditions, microglia assume an “activated” state in which they become big and round and secrete compounds that orchestrate an inflammatory response in the brain.The shape and function of microglia can be also changed following exposure to chronic unpredictable psychological stress, which is one of the leading causes of depression in humans. Importantly, the HU research recently discovered that following exposure to stress, some microglia die and the remaining cells appear small and degenerated. According to the new theory, either activation or decline of microglia can lead to depression, so the same class of drugs cannot treat the disease uniformly.Yirmiya recommends adopting a personalized medical approach in which the status of the microglia in the individual patient is established first. Based on this initial assessment, treatment with drugs that either inhibit the over-active microglia or stimulate the suppressed microglia should be employed.