The brain and the immune system

Where psychiatry and neurology meet

I have read with great interest this phenomenal article by Natasha Loder on the Economist.

In some cases, psychiatric syndromes are brought about by very 'bodily' triggers such as streptococcus infections; these conditions can be often treated with antibiotics, anti-inflammatory drugs and immunoglobulins.

Natasha delves on several examples of such immune-mediated psychiatric conditions (including PANS/PANDAS, a subset of OCD, ME/CFS) and through to the voice of patients describes the difficulties in getting a diagnosis and proper treatment. The article also features several quotes from experts and a general reflection on the state of the art of #medicine in this field.

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Why this article is in my opinion a must-read:

1. Immune-mediated psychiatric conditions are very well-known to neurologists and psychiatrists active in research but far less known in medical practice - the result is often misdiagnosis of conditions that actually have a simple and effective treatment. It is crucial to raise awareness, promote a dedicated medical education on this topic and eventually have diagnostic algorithms that routinely include a check for immune markers in any, especially acute, presentation of psychiatric symptoms

'Thomas Pollak, a senior clinical lecturer and consultant neuropsychiatrist at King’s College London, says MRI scans should probably be used on patients after their first episode of psychosis as in 5% to 6% of patients it would change the way they are treated'

2. As Natasha correctly points out, these conditions exemplify the overlap between psychiatry and neurology; for instance, many encephalitis have psychiatric symptoms but are considered neurological diseases and are often treated by neurologists, who are not always specialized in psychiatric treatment. Psychiatric symptoms emerge in a number of other diseases of the brain which are traditionally treated by neurologists, such as #Parkinson, #ataxia and #multiplesclerosis. And vice-versa, psychiatric patients have increased risk of neurological symptoms, from cognitive decline to sleep disorders.

'But many of the field’s problems could be resolved by relaxing the distinctions that exist today between neurology, which studies and treats physical, structural and functional disorders of the brain, and psychiatry, which deals with mental, emotional and behavioural disorders'.

The division between #psychiatry and #neurology, which in some countries is a real chasm, fails patients and should be reconsidered - doctors need to be able to treat the brain, regardless of the cause and type of symptoms. In this regard I want to highlight that the European Academy of Neurology and the European Psychiatric Association are since years working together to strengthen collaborations and promote joined initiatives on brain health - I was happy to attend a co-hosted session at the latest EPA meeting in Budapest, featuring EAN current president Paul Boon (in the pic), Claudio Lino Bassetti , EAN president-elect Elena Moro and EPA current president Geert Dom .

3. As a scientist, I find this topic fascinating. The fact that infections, often systemic, can trigger a psychiatric syndrome clearly indicate that the brain and the immune system are linked and that acting on one you can modulate the activity of the other. We have all collectively learned this with COVID, which can, in some individuals, elicit a post-infectious syndrome called #longCOVID. Its prevalent manifestations are neurological and psychiatric, including brainfog and depression. I have personally studied for long time the role of the immune system in #Alzheimer, and described how brain amyloidosis in this context can elicit a response in the adaptive immune system in both the brain and in blood . Even psychoactive drugs like ketamine have unexpected effects on #microglial cells, the resident immune cells in the brain responsible for synaptic pruning. Psychological and physical stressors in early life can predispose the brain for later development of psychiatric diseases, most likely through changes in microglial interaction with synapses. This phenomenon calls for a profound reconsideration of how the brain works, the mechanisms linking brain activity to inflammatory markers as well as the development of potential new, immune-related treatments. At the end of the day it highlights the fact that the brain is an organ like any other, and when it stops functioning it means there is some biological cause for it.

What I would add to the article:

1. ?The sex and gender aspect. Most post-infectious syndromes and in general neuro-immune diseases affect overwhelmingly women. There is clearly a higher vulnerability of the adult female brain to this specific class of diseases in which the immune system affects the nervous system. I did an entire TED-X talk to say that studying women in this context is a must - it's an example of how #gendermedicine can unlock new discoveries that would be missed without stratifying data by sex. Also, it should be noted that women presenting with this type of symptoms are often neglected or not believed, because of highly ingrained gender biases in the medical system. Higher awareness of these conditions would help an incredible number of women to get the treatment they need. Which leads me to my final comment:
2. Trust the patients. Immune-mediated psychiatric syndromes are often misdiagnosed or diagnosed late. In children especially, PANS/PANDAS is so little known that parents travel for years before getting an answer and encounter high level of dismissal in the process. But these diseases are real and have very real causes - we must trust the patients (and their families). This applies to psychiatry in general. I find it atrocious the recent statement by the UK government on the need to reduce 'sick notes' for mental health conditions, as allegedly we are medicalizing normal up-and-downs of life. We are not - psychiatric symptoms are real, they show that something is not working properly in the brain of patients and, exactly like any other symptom, need to be investigated and addressed. We must trust the patients and trust the science - also when it comes to the brain.

To conclude

This article is a great starting point for a global discussion on the brain (which is an organ like any other), its disease (which are real and have often identifiable organic causes) and how we want to promote brain health in the society (trusting the patients, raising awareness and improving patient pathways). There is no health without brain health - but do we really understand what brain health is?

(edited to add a few more scientific examples of brain-immune interactions)