Clinical PhD Programme at the University of Cambridge: 'Early life immune and metabolic function and psychotic symptoms in the ALSPAC birth cohort.' (360G-Wellcome-094790_Z_10_Z)

Schizophrenia is associated with proinflammatory changes (increased cytokines in serum and CSF). Recent evidence suggests important effects of hormone leptin on immune system and cognition. Cognitive dysfunction is also prominent in patients with schizophrenia. However, prospective studies are required to establish importance of inflammatory cytokines and their modulators, such as leptin in the pathophysiology of schizophrenia. Increased risk of schizophrenia is also observed among individuals exposed to immune activation or infection during early life. There is evidence, inflammatory cytokines can increase fetal exposure to maternal glucocorticoids leading to long term changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. Alterations of HPA axis functioning by early life environmental factors may be a common link between chronic diseases of adult life, such as hypertension, type 2 diabetes and schizophrenia. Besides, schizophrenia is associated with subtle alterations in motor and cognitive development early in life. Early environmental factors such as immune activation may interfere with neurodevelopment, and thus contribute to disease risk. However, effects of early life immune dysfunction on human neurodevelopment are yet to be explored. We propose a study of early life (pre and post natal) immune activation and risk of psychotic symptoms, and motor and neurocognitive development in ALCPAC birth cohort.