ABOVE: © lisa clark

One of the most well-known autoantibodies with targets in the brain is the anti-NMDAR antibody, which targets the NMDA receptor (NMDAR) that is found on excitatory neurons in the brain. When present, this autoantibody prompts neurons to engulf NMDARs and reduces these receptors’ numbers at the synapse. This dearth of NMDARs, in turn, causes problems in synaptic transmission that underlie a range of neuropsychiatric symptoms such as hallucinations, delusions, seizures, and movement abnormalities. Researchers have pinpointed more than two dozen other brain-targeting antibodies, most of which are found in patients with autoimmune disease of the central nervous system. The role these antibodies play in psychiatric illnesses such as schizophrenia is the subject of active investigation. 

Illustration comparing healthy synapse and anti-NMDAR disease
© Lisa Clark

Cytokine contributions to psychosis 

Some researchers have found higher-than-normal levels of cytokines, chemical messengers of the immune system, in people with psychosis. The mechanism through which these molecules might contribute to psychiatric symptoms remains an open question, but at least two potential pathways have been proposed: one in which cytokines act via connections with the peripheral nervous system (A) and another in which the molecules enter the brain by penetrating the blood-brain barrier (B). 

Illustration comparing neural pathway and the humoral pathway
© lisa clark

A) Neural pathway 

Cytokines in the body’s periphery may activate the vagus nerve, a large, multi-branched cluster of neurons that carries signals from the brain to various organs and vice versa. This may, in turn, trigger immune cells and chemical messengers in the brain that alter neurotransmission.

B) Humoral pathway

Inflammation may cause the blood-brain barrier to become “leaky” and allow immune cells and molecules such as cytokines to enter the surrounding brain tissue.

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