Depression – new ideas for the diagnosis and treatment

iStock_000011113599_XXXLargeIt is currently believed that depression may be caused by improper functioning of immune system cells in brain. The scientists from The Hebrew University of Jerusalem claim that treatment of depression may be revolutionized by the use of new psychotropic drugs. The results of the analysis were published in Cell Press in the section Trends in Neurosciences.

Depression affects one in six people in the same age group and it is one of the main causes of human suffering. It is also the leading global cause of disability that is measured by DALY (disability adjusted life-years) and it is ahead of cardiovascular diseases, respiratory diseases, cancer and HIV/AIDS.

Despite recent progress in understanding the molecular and cellular biological mechanisms that underlie this disease, the reason for its formation is still not known. It is believed that a large number of glial cells might be the cause. The development of new and effective antidepressants is very slow.

The newest scientific information points out that the function of microglia is essential, both in physiological processes in the brain, such as synaptic transmission and neuronal plasticity, and in brain pathology concerning neuropsychiatric disorders. Microglia constitutes 10% of all brain cells and it is considered as immune cells which are present there. Their function is to defense our brain against infectious agents such as bacteria or viruses. What is more, immune cells play an important role in the processes of regeneration and healing of brain tissue.

The newest research by Professor Yrmiya, Director of Psychoneuroimmunology Lab in The Hebrew University of Jerusalem, would have significant influence on the future development of antidepressant. Current drugs are not always effective so there is an urgent need to discover new biological mechanisms of drugs, in order to be able to reach the roots of depression. It would facilitate both diagnosis and the right treatment of patients with depression.

The scientists from The Hebrew University of Jerusalem claim that microglia disorders may lead to depression and drugs which would restore proper functioning of these cells may be effective also as fast-acting antidepressants. The scientists also affirm that human depression studies, which were conducted with the use of post-mortem brain tissue and special imaging techniques mainly positron emission tomography (PET), as well as animal depression studies have shown that when the structure and function of microglia is changed, these cells cannot control neither the processes in the brain nor behavior, and this leads to depression.

There are certain conditions in which microglia cells become active and it means that they become big and round and what is more, they excrete the compounds that coordinate inflammatory response in brain. This is observed in many diseases associated with a high incidence of depression, such as infection, trauma, aging, autoimmune diseases such as multiple sclerosis (MS), or neurodegenerative diseases (Alzheimer’s disease). The shape and function of microglia may also be modified after exposure to the chronic and unpredictable psychological stress which is one of the main causes of depression. Moreover, as Professor Yirmiya noticed during his studies, there are some microglia cells which die after exposure to the psychological stress and there are cells which turn into small and damaged cells. This confirms the existence of this dependency. These findings have both theoretical and clinical implications. According to the newest theory, both activation and atrophy of microglia may lead to depression and that is why the same class of drugs cannot be used to treat the disease evenly.

Israeli researchers have observed the existence of a significant dependency between local and common inflammation and depression. Their conclusion is that the levels of markers of common inflammation may serve as a replacement marker of microglia in the brain. Hence, patients with high levels of inflammatory markers (eg. CRP, TNF, IL-1 and IL-6) should be treated with drugs that suppress the activity of microglia, such as minocycline, TNF (infliximab) or COX-2 inhibitors (celecoxib). In turn, patients with low levels of inflammatory markers should be cured with substances which stimulate microglial cells such as M-CSF or GM-CSF.

Professor Yirmiya notes that if there are any types of depression caused by microglia disease the first thing that should be done in the treatment is to determine the status of microglia in individual patients and then start personalized medical treatment. The drugs should either suppress the overactive microglia or invigorate the one of which activity is suppressed.

The conclusions of the analysis conducted by the Jerusalem scientists allow us to look at depression as a disease with immunological etiology. This in turn opens up new depression treatment ideas. The results seem to be promising.

Written by: Agata Zwierz, Klaudia Zyzak, Katarzyna Gałaszkiewicz.

Source:
1. Raz Yirmiya, Neta Rimmerman, Ronen Reshef. Depression as a Microglial Disease. Trends in Neurosciences, 2015; 38 (10):
2. Halassa, M.M. and Haydon, P.G. (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu. Rev. Physiol. 72, 335–355
3. Kettenmann, H. et al. (2011) Physiology of microglia. Physiol. Rev. 91, 461–553
4. Tremblay, M.E. et al. (2011) The role of microglia in the healthy brain. J. Neurosci. 31, 16064–16069
5. Bayer, T.A. et al. (1999) Evidence for activation of microglia inpatients with psychiatric illnesses. Neurosci. Lett. 271, 126–128
6. Raison, C.L. et al. (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70, 31–41
7. Bauer, J. et al. (1995) Induction of cytokine synthesis and fever suppresses REM sleep and improves mood in patients with major depression. Biol. Psychiatry 38, 611–621
8. Dantzer, R. and Kelley, K.W. (2007) Twenty years of research on cytokine-induced sickness behavior. Brain Behav. Immun. 21, 153–160
9. Rothermundt, M. et al. (2001) Inflammatory markers in major depression and melancholia. J. Affect. Disord. 63, 93–102


Would You like to know more? Watch on MEDtube.net: Brain Bleed Leading to Vision Impairment

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