Neuroinflammation in Psychiatry Simplified – The Link Between the Immune System and The Brain- Dr Sanil Rege

In a previous article, Dr Sanil Rege spoke about a young girl with mania who was found to have anti-neuronal antibodies and responded to immunosuppressants.

Getting to know the Immune System

The 4 Types of T Cells

1. Th17 – extracellular bacteria, fungi, and autoimmunity
2. Th1 – intracellular pathogens and autoimmunity
3. iTreg – immune tolerance, lymphocyte homeostasis, and regulation of immune responses
4. Th2 – extracellular parasites, allergy, and asthma

Activation of Autoimmunity

Autoimmune Reaction in the Brain

Impact of Neuroinflammation on Mitochondria and Oligodendrocytes

Microglia receive inflammatory signals from the periphery which then reach the brain. Activated microglia, in turn, initiates an inflammatory cascade releasing cytokines, chemokines, inflammatory mediators, and reactive nitrogen and oxygen species (RNS and ROS) induces mutual activation of astroglia, thereby amplifying inflammatory signals within the CNS.

Cytokines, induce the enzyme, IDO (indolamine 2,3 dioxygenase), which breaks down Tryptophan, the primary precursor of 5-HT, into quinolinic acid (QUIN), a potent NMDA agonist and stimulator of Glutamate (GLU) release.

A recent meta-analysis of 101 studies studying the kynurenine pathways in Major depressive disorder, bipolar disorder and schizophrenia showed that:

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1. Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological psychiatry, 65(9), 732-741.
2. Berk, M., Kapczinski, F., et al., (2011). Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neuroscience & biobehavioral reviews, 35(3), 804-817.
3. Marx, W., McGuinness, A. J., Rocks, T., Ruusunen, A., Cleminson, J., Walker, A. J., … & Tseng, P. T. (2020). The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Molecular Psychiatry, 1-21.