The Neuroinflammatory Hypothesis

Question 1

What is this?

Answer 1

The idea that the brains immune system (migroglia) is overactive in people are risk - animal studies show a link between pro-inflammatory agents and schizophrenia symptoms. The symptoms are revered with antipsychotics or antibiotics which reduce microglial activation
This supports the evidence for prenatal or perinatal infection and increased risk

Question 2

How can this be treated?

Answer 2

Antipsychotics or antibiotics reduce microglial in the brain, reduces the symptoms

Question 3

What does this hypothesis support?

Answer 3

The early neurodevelopmental theory - that prenatal infection can increase the risk

Question 4

What are microglia?

Answer 4

The immune system of the brain

Question 5

What happens with high risk subjects?

Answer 5

PET imaging in health volunteers - high risk subjects and patients have more activation of microglial activity as the severity increases

Question 6

What have genome wide association studies showed?

Answer 6

More than 100 genes contribute to genetic risk
The dopamine receptor gene DRD2 - associated with risk
Most significant association is on chromosome 6 which includes a region containing genes involved in acquired immunity (MHC)

Question 7

What are microglia in health conditions vs threat?

Answer 7

Healthy - ramified state (thin cell bodies, made up of legs) - survey the brain for pathogens

When they see a threat, they become activated - they are ready to tackle brains

Then turn into amoeboid - peak up regulation

Question 8

What does their function go beyond?

Answer 8

The immune system - involved in lots of homeostatic functions in a healthy brain such as:
neuronal death and survival
synaptogenesis
synpatic pruning

Question 9

When does microglial respond?

Answer 9

It isn’t instant in response to infectious agents - it grows steadily throughout the life span, reaching peak in late adolescence and early adulthood

Question 10

What does a prenatal infection do?

Answer 10

Primes microglia by an early pathogen, this priming may interact with cells in the developing nervous system. May lead to a subtle rearragement of synaptic circuitry resulting in behavioural impairment in adolescence - explains why it is shown later on

Question 11

What have animal studies shown?

Answer 11

Decreased hippocampal neurogenesis in response to microglial activation

Decreased reelin (signal for neurons) expression in hippocampus, accompanied by impairments in WM and motor skills

Aberrant synapse formation as a result of microglial activation, and oligodendrocyte (myelin) loss in the frontal cortex - reversed by antipsychotics