This review describes a key role for mononuclear phagocytes in the pathogenesis of major psychiatric disorders. There is accumulating evidence for activation of microglia (histopathology and PET scans) and circulating monocytes (enhanced gene expression of immune genes, an overproduction of monocyte/macrophage-related cytokines) in patients with bipolar disorder, major depressive disorder, and schizophrenia. These data are strengthened by observations in animal models, such as the MIA models, the chronic stress models, and the NOD mouse model. In these animal models of depressive-, anxiety-, and schizophrenia-like behavior, similar activations of microglia and circulating monocytes can be found. These animal models also make in-depth pathogenic studies possible and show that microglia activation impacts neuronal development and function in brain areas congruent with the altered depressive and schizophrenia-like behaviors.

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These observations are consistent with a role for 5-HT in mediating sustained antidepressant activity of ketamine in the FST. Molecular and cellular changes induced by ketamine may produce a rapid adaptation of 5-HT transmission which underlies the antidepressant response.

It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.