Early-Life Adversity, Systemic Inflammation and Comorbid Physical and Psychiatric Illnesses of Adult Life.

Recently, the evidence of increased immune activation in patients with schizophrenia has suggested a role for the immune system in the development of psychosis. However, what is causing this increased immune activation and how this leads to the development of psychopathology remain still unclear. In this chapter we discuss the evidence about the role of childhood trauma as possible underlying cause of the increased immune activation in patients with schizophrenia. According to preclinical and clinical models, early adverse events can disrupt the homeostatic control of immune responses and lead to enduring inflammatory dysregulation at a peripheral and central level. In fact, persisting systemic inflammation may facilitate peripheral tissues damage and breach the blood-brain barrier, leading to microglia activation and to neuroinflammation.Such chronic immune dysregulation also appear to partially explain the frequent comorbidity between psychosis and metabolic abnormalities, which have previously mainly considered as side effect of antipsychotic treatment.Overall, this evidence suggests that early stress may contribute to development of schizophrenia spectrum disorders through a modulation of the peripheral and central immune system and support the immune pathways as possible future therapeutic approach for psychosis.