Immuno-psychiatry

[1][2][3] In 1876 Alexandar Rosenblum, and later in the 1880s Dr. Julius Wagner-Jauregg, observe patients with neurosyphilis, syphilis that had spread to the nervous system, have decreased symptoms of psychosis after contracting malaria.

[1]  Moritz Tramer then reports how schizophrenia is associated with a child being born in the winter or spring months (when influenza is most commonly contracted).

In his 1892 book, "The Principles and Practice of Medicine," he observed that clinical patients with progressive septicemia showed "early delirium and marked mental prostration and apathy.

Many of these early studies in sickness behavior showed significant differences in the many pro-inflammatory cytokines reviving interest into the role that the immune system played in psychiatric disorders.

[6] Additionally, cytokines interferon-alpha and IL-6 can cause reversible reductions in brain levels of tetrahydrobiopterin (used in the serotonin, dopamine, and norepinephrine synthesis pathways).

[6] On a molecular level, cytokines effect the glutamate metabolism of the nervous system and can lead to structural changes involving microglia similar to those seen in depressed patients.

This loss of oligodendrocytes (the astrocytes and microglia mentioned before) are a key marker in structural analysis of the brains of depressed patient populations.

And multiple studies have shown that “altered HPA stress responsivity being associated with increased risk of psychopathology” such as in the study of human brain cell, gathered post-mortem, mRNA was harvested in patients who had killed themselves with either a history or a lack of a history of early childhood stresses revealed significant epigenetic changes in glucocorticoid receptor expression.

Additional experimental support of giving an antidepressant prior to injection of endotoxin, a substance known to cause systemic inflammation) was also found to reduce self-reported symptoms of depression.

[1] Following studies revealing kynurenic acid's uniqueness as being the NMDA receptor's only endogenous (naturally found in the body) antagonist, and the fact that psychosis can be elicited from NMDA receptor antagonism, multiple studies investigated and confirmed change levels of this kynurenic acid may be related to psychosis.

Blood–brain barrier methods of transport. Given the large and charged size of cytokines, active transport is the only direct way for the same cytokine circulating in the blood to pass through an intact blood-brain barrier. Other methods, such as activation of the endothelial cells, cytokine signaling, recruitment of granulocyte cells, and activation of afferent neurons work indirectly and cause the creation or release cytokines. [ 7 ]