title: Childhood Epstein-Barr Virus infection and subsequent risk of psychotic experiences in adolescence: a population-based prospective serological study.
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.
authors.affiliation: 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.
authors.forename: Golam M
authors.initials: GM
authors.lastname: Khandaker
authors.affiliation: Department of Psychiatry, University of Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Stochl
authors.affiliation: 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.
authors.forename: Stanley
authors.initials: S
authors.lastname: Zammit
authors.affiliation: 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.
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
authors.affiliation: Department of Psychiatry, University of Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007360:Intelligence; D007361:Intelligence Tests; D007406:Interview, Psychological; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000097:blood* / Q000453:epidemiology*; D012306:Risk
chemical_list: D007074:Immunoglobulin G
keywords: ALSPAC birth cohort; Epstein-Barr Virus; Herpes Simplex Virus; IQ; IgG antibody; Neurodevelopment; Psychotic experiences; Schizophrenia risk; Serology