Neuroimmunology

Question 1

Immunopsychiatry / Neuroimmunology

Answer 1

Study of the connection between the brain and the immune system

Question 2

Basic Premise of the Immunopsychiatry Lecture

Answer 2

Autoimmune response to infection is associated with a transdiagnostic biological vulnerability to psychiatric disorders

Question 3

Evidence for Immunopsychiatry link

Answer 3

i) Infection,
ii) autoimmune disorders and
iii) elevated markers of inflammation
are all risk factors for later psychiatric disorders

And other way round: stress disorder -> increased risk of autoimmune disease

Question 4

What kinds of psychiatric disorders are implicated in neuroimmunology?

Answer 4

Mood disorders, stress disorders, Schizophrenia, and more

Thought to induce ‘transdiagnostic vulnerability’, rather than any specific disorder

Question 5

Increased risk of Schizophrenia following hospitalisation with infection?

Answer 5

50% higher

Even more if the infection was bacterial

Question 6

Autoimmune diseases

Answer 6

Over 100 of them

In brain, blood, nerves, muscles, bones, lungs, skin etc.

Question 7

True or False: the link between psychosis and immunology has only recently been noticed

Answer 7

False

Long history in medicine going back over 100 years

Question 8

Evidence for Plausible Causal Link (infection -> psychiatric disorders)

Answer 8

Immunological inflammation induces fatigue, withdrawal, depression-like symptoms etc. Potentially evolutionary advantageous behaviour induced by immune system

Increased biomarkers of inflammation in the blood and CSF found for many psychiatric disorders. Specifically increased levels of cytokines found in patients with SCZ and especially MDD

Cytokines given as a cancer treatment; been found to increase depression in these patients

Animal models: administration of immune stimuli and cytokines induces depression-like symptoms in mice. Similar results with SCZ

Question 9

Causation Problem

Answer 9

Chickens, eggs, yada yada: causation is not clear, probably bidirectional

Immune response could be defending against an oncoming disorder: maybe we only see the people who have an unsuccessful response

Question 10

Two types of immunity

Answer 10

Innate immunity: rapid response to infection
T cells and many more

Adaptive immunity: slow response to infection
T cells, B cells, antibodies

Question 11

NMDA receptor (NDMAR)

[Expect a question on this!]

Answer 11

Glutamate system

‘Coincidence detector’ crucial for learning and memory

NDMAR antibodies (especially in CA1 area in hippocampus) can cause reduced NMDAR density

Question 12

Anti-NMDA receptor encephalitis

[Expect a question on this!]

Answer 12

Classic neuropsychiatric syndrome: brain inflammation caused by antibodies

Killed cuddly Berlin boi, Knut

80% female, mean onset 21 years

Typical progression: viral infection -> psychiatric symptoms (esp. psychosis) -> coma -> long-term deficits

Question 13

Neuroimmunological effects of anti-NMDA receptor encephalitis

Answer 13

Possible link between a (‘paraneoplastic’) subtype of the condition and developing various psychiatric symptoms

Question 14

Clinical Relevance of it all

Answer 14

Diagnosis?
Using immunological biomarkers? Maybe, but it’s difficult. Likely that by the time you find out that inflammation caused SCZ, it happened 15 years ago so info is not that helpful

Therapy?
Some evidence that some anti-inflammatory treatments (including cytokine inhibitors) could be effective for SCZ or especially MDD.
Might find ‘inflammatory subtypes’ for whom this kind of treatment works.