title: Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study.
abstract: OBJECTIVE
  Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear.
  
  
  OBJECTIVE
  To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis.
  
  
  METHODS
  The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments.
  Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years.
  
  
  METHODS
  Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule-Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview.
  
  
  RESULTS
  After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner.
  
  
  CONCLUSIONS
  Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, England2National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, England3Collaboration for Leadership in Applied Health Research and Care, East of England, Cambri.
authors.forename: Golam M
authors.initials: GM
authors.lastname: Khandaker
authors.affiliation: Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, Bristol, England.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Pearson
authors.affiliation: Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, Bristol, England6Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric.
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, Bristol, England7Division of Psychiatry, University College London, London, England.
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, England2National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, England3Collaboration for Leadership in Applied Health Research and Care, East of England, Cambri.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002648:Child; D003863:Depression / Q000097:blood* / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007406:Interview, Psychological; D008297:Male; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood* / Q000453:epidemiology; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein