SYMPOSIUM 3: Microglia role in neuropsychiatric disease and its potential as a treatment target

(chaired by Valeria Mondelli & Peter Talbot)


Given that clinical, genetic and pharmacological findings indicate that inflammatory molecules and their associated pathways are enhanced in neuropsychiatric disorders such as major depressive disorder and schizophrenia, Monday morning’s symposium 3 dealt with the importance of microglia cells in these disorders. Microglia are immune cells within the central nervous system and respond to neuroinflammation as the native immune cells defending organism homeostasis against pathogens. As such, current anti-inflammatory drugs and novel immune mediators are prospective targets for modulating the microglia system for treating these psychiatric ailments. Our speakers gave an introduction to this and how successful these prospective treatments are fairing in clinical trials.


  1. Peripheral and central inflammation in patients with psychiatric disorders: what is relevant for future treatment strategies (Valeria Mondelli, King’s College London)

Given the high incidence of immune mediators in both the peripheral and central nervous systems, the co-chair opened proceedings by guiding us through which components are relevant for prospective psychiatric treatments and whether these systems are linked. Her methods included quantifying certain immune markers in treatment-resistant, treatment-responsive and drug-naïve depressive and schizophrenic patients. She presented that the peripheral immune marker high sensitive C reactive protein was enhanced in treatment-resistant depressed patients, whilst interleukin-6 levels were increased in treatment-resistant schizophrenics. Hence, these studies demonstrate increased neuroinflammation in these disorders, particularly in treatment-resistant patients. As this field is still in its relevant infancy, future studies will need to elucidate link between peripheral and central immune mediators in neuropsychiatry. In addition, how putative antidepressants such as ketamine and minocycline, an immune mediator suppressing viral replication by reducing T cell activation, affect microglia will be interesting and relevant to discover in the near future.


  1. Innate immunity as a treatment target in neuropsychiatric disorders (Josef Priller, University of Edinburgh)

Josef Priller opened by telling us that immune modulation of psychiatry disorders has been successful over one century ago as neurosyphilis symptoms were improved with immune modulators. Now that clinical trials with the anti-alpha4 integrin ligand natalizumab is being tried to treat schizophrenia, innate immunity modulators are now being tested in this century. He then detailed the maternal immune activation model in non-human species as a primer for psychiatric disorders. By activating the material immune system and altering her microbiome during pregnancy, offspring develop a compulsive-like phenotype and increased microglial activation. Interestingly, these neurodevelopment, behavioural and decreased neurogenesis effects can be attenuated by minocycline administration. Indeed, minocycline has been shown to improve rodent schizophrenic-relevant negative and cognitive phenotypes. However, minocycline has not always been associated with positive outcomes in these recent human studies. As a result of reduced TSPO binding to increase p-NFL levels, a harmful effect of this drug was found in traumatic brain injury sufferers. Minocycline and aspirin co-adminstration is also been tried in bipolar patients.

Finally, Priller finishing by introducing the new era of deep immunoprofiling and GWAS (genome-wide association studies) for probing heterogeneous immune factors in schizophrenia to help identify new drug targets for the disorders.

A question regarding the use of minocycline in treatment clinical schizophrenic populations after the presentation was not answered completely as Bill Deakin, BAP lifetime award winner of 2017, would give a talk on exactly that topic later on Monday.


  1. Targeting neuroinflammation in schizophrenia using monoclonal antibodies (Tiago Reis Marques, Imperial College London)

Dr Marques introduced his talk with some interesting points regarding inflammation in schizophrenia including:

  1. Microglia activity is correlated to psychosis onset
  2. Inflammation markers including microglia ones are increased in schizophrenia
  3. Current dopamine D2 antagonist antipsychotics do not appear to be better than placebo for reduce this inflammation
  4. One case study revealed that bone marrow donation of allogenic stem cell transplants from one schizophrenic brother to his 67 year old leukaemia-affect, schizophrenic-unaffected brother resulted also in transplantation of the schizophrenic condition. This is substantial evidence that the immune system is implicated in schizophrenia pathogenesis. Sadly that transplanted patients committee suicide two years after receiving the transplanted due to schizophrenic-associated positive symptoms.

Based on those introductory slides, Marques asked whether enhanced microglia activation in schizophrenia can be specifically modulated by monoclonal antibodies. To elucidate this a drug-placebo control study is necessary. The antibody Aducanumab has been previously shown to reduce amyloid beta plaques in Alzheimer’s disease, so Marques and colleagues will undertake a 3 month long trial in schizophrenic patients to include treatment success ratings, neuroimaging and cerebrospinal fluid measurements. Come back in a few years to BAP to find out how the trial goes!


  1. Does innate immunity activation contribute to the pathogenesis of Alzheimer’s disease? (Michael Heneka, University of Bonn)

This symposium was concluded with Michael Heneka, a world leader in the neuroinflammation of neurodegenerative disorders such as Alzheimer’s disease (AD). He opened by telling us about the role of microglia attacking bacteria and the history of how Congo red staining facilitated quantifiably measuring bacteria levels.

The NLRP3 inflammasome system is activated in AD which is mediated majorly by the apoptosis factor caspase-3. Knockout of factors in this system result in reduced AD-like phenotypes and associated characteristics in mice. Amyloid-beta sheets are dangerous to microglia as they enhance neuroinflammation via inflammasome activation. AD amyloid-beta plaques require ASC, a molecule released by microglia which bind to amyloid-beta peptides,  plaque aggregate and drive disease progression. Heneka’s group is ongoing in their search for discovering more important factors which facilitate AD progression in the bid to identify putative treatment targets for this destructive neurodegeneration disease.

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