Golam M Khandaker1, Jan Stochl2, Stanley Zammit3, Glyn Lewis4, Peter B Jones2. 1. Department of Psychiatry, University of Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK; Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, UK. Electronic address: gmk24@medschl.cam.ac.uk. 2. Department of Psychiatry, University of Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK. 3. Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, UK; Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK. 4. Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, UK; Division of Psychiatry, University College London, UK.
Abstract
BACKGROUND: Several studies suggest a link between early-life infection and adult schizophrenia. Cross-sectional studies have reported: (1) increased prevalence of Epstein-Barr Virus (EBV), a member of the Herpesviridae family in schizophrenia; (2) a possible role of Herpes simplex virus in cognitive dysfunction in schizophrenia and healthy controls. We report a longitudinal serological study of early-life EBV infection, childhood IQ, and subsequent risk of psychotic experiences (PE) in adolescence. METHODS: Serum antibodies to EBV (anti-VCA IgG) were measured in 530 participants from the ALSPAC cohort at age 4 years. Assessments for IQ at age 9 and PE at age 13 were attended by 401 and 366 of these individuals, respectively. Logistic regression calculated odds ratio (OR) for PE in EBV-exposed, compared with unexposed group. Mean IQ scores were compared between these groups; effect of IQ on the EBV-PE association was examined. Potential confounders included age, gender, ethnicity, social class, household crowding, and concurrent depression and anxiety. RESULTS: About 25% of the sample was exposed to EBV at age 4. EBV exposure was associated with subsequent risk of definite PE in adolescence; OR 5.37 (95% CI 1.71-16.87), which remained significant after confounding adjustment. EBV-exposed individuals compared with unexposed performed worse on all IQ measures; mean difference in full-scale IQ 4.15 (95% CI 0.44-7.87); however, this was explained by socio-demographic differences. The EBV-PE association was not explained by IQ. CONCLUSIONS: Early-life exposure to EBV is associated with PE in adolescence, consistent with a role of infection/immune dysfunction in the aetiology of psychosis.
BACKGROUND: Several studies suggest a link between early-life infection and adult schizophrenia. Cross-sectional studies have reported: (1) increased prevalence of Epstein-Barr Virus (EBV), a member of the Herpesviridae family in schizophrenia; (2) a possible role of Herpes simplex virus in cognitive dysfunction in schizophrenia and healthy controls. We report a longitudinal serological study of early-life EBV infection, childhood IQ, and subsequent risk of psychotic experiences (PE) in adolescence. METHODS: Serum antibodies to EBV (anti-VCA IgG) were measured in 530 participants from the ALSPAC cohort at age 4 years. Assessments for IQ at age 9 and PE at age 13 were attended by 401 and 366 of these individuals, respectively. Logistic regression calculated odds ratio (OR) for PE in EBV-exposed, compared with unexposed group. Mean IQ scores were compared between these groups; effect of IQ on the EBV-PE association was examined. Potential confounders included age, gender, ethnicity, social class, household crowding, and concurrent depression and anxiety. RESULTS: About 25% of the sample was exposed to EBV at age 4. EBV exposure was associated with subsequent risk of definite PE in adolescence; OR 5.37 (95% CI 1.71-16.87), which remained significant after confounding adjustment. EBV-exposed individuals compared with unexposed performed worse on all IQ measures; mean difference in full-scale IQ 4.15 (95% CI 0.44-7.87); however, this was explained by socio-demographic differences. The EBV-PE association was not explained by IQ. CONCLUSIONS: Early-life exposure to EBV is associated with PE in adolescence, consistent with a role of infection/immune dysfunction in the aetiology of psychosis.
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