The Link Between the Immune System, Environment, and Psychosis

The last decade has witnessed a burgeoning interest in studies exploring the link between psychosis spectrum disorders (PSD) and altered immune function. While epidemiological and clinical studies point to evidence for increased peripheral inflammatory markers in PSD, it is not clear whether peripheral inflammation correlates with central inflammation in the brain. Furthermore, these studies are confounded by multiple methodological and disorder-related factors such as antipsychotic medications, smoking, obesity, and metabolic syndrome, all of which independently contribute to altered inflammation. Clinical and animal studies provide encouraging evidence that inflammatory processes can define trans-diagnostic neuropsychiatric domains such as positive/negative valence, affective dysregulation, and cognitive impairment. In this commentary, we speculate on whether inflammation-mediated pathways may serve as a final-common pathway for environmental risk factors of early-childhood adversity, adolescent cannabis use, social exclusion, and on the possible mechanisms mediating the pathophysiology of PSD. We propose an integrative framework and suggest future research strategies that may help disentangle the link between immune dysfunction and PSD.