Tuesday, September 02, 2014

Cytokines and Psychiatry- Few facts


    At a time when the only thing the people are interested in Ebola, it is probably very difficult to impress the fact that more is there on infectious literature. There is no doubt that at this point it is a global priority and hence rightly the interest. Leaving the trend aside, I have many a times in this post talked about the possible role of microbes in psychiatric conditions. For example, there probably is a good possibility that toxoplasma (Link), Endogenous retrovirus (Link) or other microbes (Link) can influence.

   It is been a question for me to think, how can a microbe after all influence a neurochemical process? Of course the answer doesn't look straightforward. But as far as I could gain from current evidence, in some cases at least there looks to be an immunology component influencing. There has been a number of studies more recently concentrated on studying the immunological parameters in psychiatry. The field referred to as PNI (Psychoneuroimmunology) probably will help us uncover more facts. So, I have put together a few important points in this post, that let me argue that immune cytokines and psychiatry have some relation

   In my opinion, the point that Central Nervous System (CNS), is highly protected from immunology is probably because the mediators of immune system, have tremendous cross signalling with important neural functions. It thus also makes sense to me argue that Blood Brain Barrier (BBB), strictly polices the signalling molecules. But the potential of cytokines to be involved with BBB regulation is not well studied. Recently a study published in mBio, studied the importance of PRR (Pattern recognition receptor) in context with West Nile Virus and BBB regulation. The study found that interleukins such as IL-1, can cause loss of BBB integrity and additional lymphocyte trafficking. It occurred to me if interleukin dysregulation alone could explain a lot of psychiatric condition based on following.

1. Infections in prenatal period that induced large quantities of inflammatory cytokines (especially IL-6 and IL 8) in the mother during pregnancy, especially during the 2nd trimester is a known risk factor for schizophrenia.
2. Cytokines have shown to directly influence brain developments in hippocampal regions, which is linked with schizophrenia.
3. Interleukin levels are known to effect and alter neurotransmitters especially serotonin and glutamate.
4. Patients treated with Interferon γ, for HCV infection develop significant mood disorders overtime.
5. Commonly used antidepressant drugs (reboxetine, desipramine, fluoxetine and clomipramine) show anti-inflammatory properties.
6. People administered immunomodulatory drugs with standard anti-psychotic therapy show better response.

      It is very tempting to say that dys-regulated immune function in the CNS can explain a lot of psychiatry conditions. To show how this works, let me try a very simple example. Imbalance in TH1/TH2 response is known to effect IDO (Indoleamine 2, 3-Dioxygenase), effecting the Tryptophan – Kynurenine metabolism. The final product, quinolinic acid directly antagonizes the NMDA receptor, and probably subsequent schizophrenia.

     But yes, the question still remains as to how the immune system comes to be deregulated in the first place. I don't have a good answer for that yet, but thats a good question to begin asking.

Muller, N., & J. Schwarz, M. (2010). The Role of Immune System in Schizophrenia Current Immunology Reviews, 6 (3), 213-220. PMID: 21057585

Gray SM, & Bloch MH (2012). Systematic review of proinflammatory cytokines in obsessive-compulsive disorder. Current psychiatry reports, 14 (3), 220-8 PMID: 22477442

Daniels BP, Holman DW, Cruz-Orengo L, Jujjavarapu H, Durrant DM, & Klein RS (2014). Viral Pathogen-Associated Molecular Patterns Regulate Blood-Brain Barrier Integrity via Competing Innate Cytokine Signals. mBio, 5 (5) PMID: 25161189

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