Microglia May Be Behind Some Forms of Depression

The new theory supports a more personalized approach to the treatment of depression.

Depression is not a one-size-fits-all disease, and now researchers from the Hebrew University of Jerusalem are calling for a more personalized approach to depression treatment.

In a review paper published in Trends in Neurosciences, researchers suggest that some forms of depression should be considered as a microglial disease, and therefore be treated with a different class of antidepressants that either inhibit or stimulate microglial status dependent on the patient’s depression.

“Our views on microglia have dramatically changed over the last decade,” said review author Prof. Raz Yirmiya, director of the Hebrew University’s Laboratory for PsychoNeuroImmunology. “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.”

“Studies in humans, using post-mortem brain tissues 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,” he said.

CLINICAL CHART: Psychotropic Drug Indications

The researchers note that many conditions induce microglial activation, including various bacterial and viral infections, brain trauma, and neurodegenerative diseases, which trigger an inflammatory response in the brain. In other cases, such as chronic psychological stress, microglia die or become small and degenerated. The researchers theorize that both activation and decline of microglia can lead to depression. These forms of depression, they suggest, could be considered “microglioplathies.”

Notably, the microglial inhibitor minocycline has been found to attenuate lipopolysaccharide (LPS)-induced depressive symptoms in illness-associated depression, while anti-inflammatory drugs have shown promise in attenuating an HIV-induced neurobehavioral syndrome with depressive qualities.

“Deviations from microglial homeostasis should be regarded as important therapeutic targets for major depression,” the authors wrote. “This implies that depression cannot be treated uniformly, but should instead be treated by a personalized medical approach based on the microglial status of the individual depressed patient.”

The researchers suggest that future studies should focus on the development of diagnostic procedures that are reasonable for routine use in the identification of microglial status.


  1. Yirmiya R et al. Trends Neurosci. 2015; doi:10.1016/j.tins.2015.08.001.