Multiple lines of evidence suggest early life environmental factors play an important role in the aetiology of schizophrenia. Environmental insults operating in pre and post natal period can interfere with brain development, which can lead to long-term changes in subsequent brain and behavioural development by altering neurodevelopmental trajectories. Impaired neurodevelopment in childhood and risk of future schizophrenia have been demonstrated in several birth cohorts.1 Childhood CNS infections (early environmental factor) and increased risk of schizophrenia also has been reported from prospective studies.2, 3 It has been postulated that proinflammatory cytokines, and their modulators such as leptin may be associated with risk of schizophrenia, and cognitive dysfunction via their effects on the glutamatergic system.4

We propose a prospective study in ALSPAC birth cohort to test the hypotheses that that immune and metabolic dysfunction in early life increases the risk of psychotic symptoms (PLIKS), and affects childhood neurocognitive development (e.g. I.Q., working memory, attention). To our knowledge this would be the first prospective, and population-based study of immune and metabolic function in relation to risk of psychosis.

Investigation of early life risk factors, such as immune and metabolic function will be important to understand the neurobiology of schizophrenia. There will be also scope for prevention and public health interventions, as immune and metabolic dysfunctions are potentially modifiable risk factors. Besides, this may provide important clues to a link between chronic physical and neuropsychiatric illnesses of adult life. Raised inflammatory markers have been associated with established risk factors for cardiovascular disease and diabetes in ALSPAC and other cohorts. Risk of cardiovascular disease and diabetes is higher in patients with schizophrenia, which persists even after controlling for life style, antipsychotic medication, and other risk factors. This suggest a common origin for adult chronic disorders, where early life environment play crucial role.

We briefly describe below the evidence linking immune and metabolic dysfunction and schizophrenia from human epidemiological and animal model studies.

Reference:

1. Jones P, Rodgers B, Murray R, Marmot M: Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 1994; 344(8934):1398-402

2. Rantakallio P, Jones P, Moring J, Von Wendt L. Association between central nervous system infections during childhood and adult onset schizophrenia and other psychoses: a 28-year follow-up.Int J Epidemiol. 1997 Aug;26(4):837-43.

3. Dalman C, Allebeck P, Gunnell D, Harrison G, Kristensson K, Lewis G, Lofving S, Rasmussen F, Wicks S, Karlsson H. Infections in the CNS during childhood and the risk of subsequent psychotic illness: a cohort study of more than one million Swedish subjects.Am J Psychiatry. 2008 Jan;165(1):59-65.

4. Miuller N, Schwarz MJ. The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view.J Neural Transm Suppl. 2007;(72):269-80.