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

  • Maria Antonietta Nettis
  • Carmine M. Pariante
  • Valeria MondelliEmail author
Part of the Current Topics in Behavioral Neurosciences book series


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.


Childhood maltreatment Childhood trauma Comorbidities Immune activation Inflammation Metabolic abnormalities Psychosis Schizophrenia 



This work has been supported by the South London and Maudsley (SLaM) NHS Foundation Trust & Institute of Psychiatry NIHR Biomedical Research Centre (BRC) for Mental Health; a strategic award from the Wellcome Trust (Consortium of Neuroimmunology of Mood Disorders and Alzheimer’s Disease); and the grants ‘Persistent Fatigue Induced by Interferon-alpha: A New Immunological Model for Chronic Fatigue Syndrome’ (MR/J002739/1), and ‘Immuno-psychiatry: a consortium to test the opportunity for immunotherapeutics in psychiatry’ (MR/L014815/1), from the Medical Research Council (UK).


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Maria Antonietta Nettis
    • 1
    • 2
  • Carmine M. Pariante
    • 1
    • 2
  • Valeria Mondelli
    • 1
    • 2
    • 3
    Email author
  1. 1.King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological MedicineLondonUK
  2. 2.National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College LondonLondonUK
  3. 3.Maurice Wohl Clinical Neuroscience InstituteLondonUK

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