Overlapping evidence of innate immune dysfunction in psychotic and affective disorders

Disturbances of the immune system and immune responses after activation are a common finding in neuropsychiatric disorders. Psychotic and affective disorders such as major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BD) also share high rates of comorbidity with inflammatory and metabolic disorders. Evidence of elevated circulating inflammatory cytokines, altered numbers and function of immune cells, and evidence of neuroinflammation including activation of microglia in the brain have been found in patients with SCZ, BD and MDD. Often these findings correlate to psychological state at the time of measurement. However, significant variation exists across these studies in many aspects, creating challenges in identifying a specific signature of immune dysfunction in these disorders. Innate immune dysfunction, and alterations in monocytes, the critical sentinel cells of the innate immune system, have been seen repeatedly in all three of these disorders, with frequent overlap in findings. In this review, dysfunction specific to the innate arm of the immune system is compared for overlapping evidence across three major psychotic and affective disorders.