The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life: A Population-Based Longitudinal Study
Open accessAbstract
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MEASUREMENT OF EXPOSURE: Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Fludrocortisone, a mineralocorticoid receptor agonist, has been shown to accelerate the onset of action of standard antidepressants in one randomized controlled trial 79”
From Major depressive disorder (2016) · cites this paper as [79]
Experimental — accuracy not yet measuredIn the citing paper
“Indeed, about a third of all depressed patients seem to express CRP levels > 3.0 mg/L [86,119,120].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [120]
In the citing paper
“The idea that stress itself induces endocrine mediators like IL6, which is traditionally associated with inflammation, has since been supported by the detection of increased circulating cytokines in depression and anxiety (Felger and Lotrich, 2013; Khandaker et al., 2014), and by the association of IL6 polymorphisms in individuals with depression (Zhang et al., 2016).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Khandaker et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.593 · Cited by 20,391
The Strengths and Difficulties Questionnaire: A research note
Goodman, R. (1997) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1997.tb01545.x · Cited by 14,908
Multiple imputation using chained equations: Issues and guidance for practice
White, I. R., Royston, P., & Wood, A. M. (2011) · Statistics in Medicine · doi:10.1002/sim.4067 · Cited by 9,792
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., & Wang, P. S. (2003) · JAMA · doi:10.1001/jama.289.23.3095 · Cited by 7,988
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus
Pradhan, A. D. (2001) · JAMA · doi:10.1001/jama.286.3.327 · Cited by 4,433
Immunobiology: the immune system in health and disease
(1995) · Choice Reviews Online · doi:10.5860/choice.32-3876 · Cited by 4,111
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848
Danesh, J., Wheeler, J. G., Hirschfield, G. M., Eda, S., Eiriksdottir, G., Rumley, A., Lowe, G. D. O., Pepys, M. B., & Gudnason, V. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032804 · Cited by 2,953
Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766
Belmaker, R. H., & Agam, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra073096 · Cited by 2,166
Saha, S., Chant, D., & McGrath, J. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.10.1123 · Cited by 2,065
(1995) · International Journal of Methods in Psychiatric Research · Cited by 1,847
Measuring the global burden of disease
Murray, C. J. L., & Lopez, A. D. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1201534 · Cited by 1,818
Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects
Miller, B. J., Buckley, P., Seabolt, W., Mellor, A., & Kirkpatrick, B. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.013 · Cited by 1,742
Risk of Cardiovascular Events Associated with Selective COX-2 Inhibitors
Mukherjee, D. (2001) · JAMA · doi:10.1001/jama.286.8.954 · Cited by 1,741
Lewis, G., Pelosi, A. J., Araya, R., & Dunn, G. (1992) · Psychological Medicine · doi:10.1017/s0033291700030415 · Cited by 1,487
Self-citationCytokine-Associated Emotional and Cognitive Disturbances in Humans
Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365
C-reactive protein, fibrinogen, and cardiovascular disease prediction
The Emerging Risk Factors Collaboration (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1107477 · Cited by 1,150
Fetal and infant origins of adult disease
Barker, D. J. P. (2001) · Monatsschrift Kinderheilkunde · doi:10.1007/s001120170002 · Cited by 1,042
Continuities and discontinuities in psychopathology between childhood and adult life
Rutter, M., Kim‐Cohen, J., & Maughan, B. (2006) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2006.01614.x · Cited by 824
Müller, N., Schwarz, M. J., Dehning, S., Douhe, A., Cerovecki, A., Goldstein-Müller, B., Spellmann, I., Hetzel, G., Maino, K., Kleindienst, N., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001805 · Cited by 794
Depressed Affect, Hopelessness, and the Risk of Ischemic Heart Disease in a Cohort of U.S. Adults
Anda, R. F., Williamson, D. F., Jones, D., Macera, C., Eaker, E. D., Glassman, A. H., & Marks, J. S. (1993) · Epidemiology · doi:10.1097/00001648-199307000-00003 · Cited by 770
Inflammatory Biomarkers, Hormone Replacement Therapy, and Incident Coronary Heart Disease
Pradhan, A. D., Manson, J. E., Rossouw, J. E., Siscovick, D. S., Mouton, C. P., Rifai, N., Wallace, R. B., Jackson, R. D., Pettinger, M. B., & Ridker, P. M. (2002) · JAMA · doi:10.1001/jama.288.8.980 · Cited by 683
Kendler, K. S. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830110060007 · Cited by 676
Danesh, J., Kaptoge, S., Mann, A. G., Sarwar, N., Wood, A., Angleman, S. B., Wensley, F., Higgins, J. P. T., Lennon, L., Eiriksdottir, G., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050078 · Cited by 676
Benros, M. E., Nielsen, P. R., Nordentoft, M., Eaton, W. W., Dalton, S. O., & Mortensen, P. B. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11030516 · Cited by 582
Autoimmune Diseases and Severe Infections as Risk Factors for Mood Disorders: A Nationwide Study
Benros, M. E., Waltoft, B. L., Nordentoft, M., Østergaard, S. D., Eaton, W. W., Krogh, J., & Mortensen, P. B. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.1111 · Cited by 572
Gimeno, D., Kivimäki, M., Brunner, E. J., Elovainio, M., De Vogli, R., Steptoe, A., Kumari, M., Lowe, G. D. O., Rumley, A., Marmot, M. G., et al. (2009) · Psychological Medicine · doi:10.1017/s0033291708003723 · Cited by 561
Wellcome Trust Case Control Consortium, Green, E. K., Grozeva, D., Jones, I., Jones, L., Kirov, G., Caesar, S., Gordon-Smith, K., Fraser, C., Forty, L., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.49 · Cited by 526
Elevated C-Reactive Protein Levels, Psychological Distress, and Depression in 73 131 Individuals
Wium-Andersen, M. K., Ørsted, D. D., Nielsen, S. F., & Nordestgaard, B. G. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.102 · Cited by 489
Khandaker, G. M., Zimbron, J., Lewis, G., & Jones, P. B. (2012) · Psychological Medicine · doi:10.1017/s0033291712000736 · Cited by 468
Self-citationPrerequisites for cytokine measurements in clinical trials with multiplex immunoassays
de Jager, W., Bourcier, K., Rijkers, G. T., Prakken, B. J., & Seyfert‐Margolis, V. (2009) · BMC Immunology · doi:10.1186/1471-2172-10-52 · Cited by 428
Müller, N., Riedel, M. J., Scheppach, C., Brandstätter, B., Sokullu, S., Krampe, K., Ulmschneider, M., Engel, R. R., Möller, H., & Schwarz, M. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.6.1029 · Cited by 388
Zammit, S., Kounali, D., Cannon, M., David, A. S., Gunnell, D., Heron, J., Jones, P. B., Lewis, S., Sullivan, S., Wolke, D., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12060768 · Cited by 319
Chaudhry, I. B., Hallak, J. E. C., Husain, N., Minhas, F., Stirling, J., Richardson, P., Dursun, S. M., Dunn, G., & Deakin, J. F. W. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881112444941 · Cited by 284
Childhood infection and adult schizophrenia: A meta-analysis of population-based studies
Khandaker, G. M., Zimbron, J., Dalman, C., Lewis, G., & Jones, P. B. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.05.023 · Cited by 257
Self-citationBirth Weight, Schizophrenia, and Adult Mental Disorder
Abel, K. M., Wicks, S., Susser, E., Dalman, C., Pedersen, M. G., Mortensen, P. B., & Webb, R. T. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.100 · Cited by 216
Prevalence of diabetes and impaired glucose tolerance in patients with schizophrenia
Bushe, C., & Holt, R. I. G. (2004) · The British Journal of Psychiatry · doi:10.1192/bjp.184.47.s67 · Cited by 212
Matthews, K. A., Schott, L. L., Bromberger, J. T., Cyranowski, J. M., Everson-Rose, S. A., & Sowers, M. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.08.005 · Cited by 132
Tzoulaki, I., Järvelin, M., Hartikainen, A., Leinonen, M., Pouta, A. M., Paldanius, M., Ruokonen, A., Canoy, D., Sovio, U., Saikku, P., et al. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn105 · Cited by 105
Knudsen, L. S., Christensen, I. J., Lottenburger, T., Svendsen, M. N., Nielsen, H. J., Nielsen, L., Hørslev‐Petersen, K., Jensen, J. B., Kollerup, G., & Johansen, J. S. (2008) · Biomarkers · doi:10.1080/13547500701615017 · Cited by 86
Dopamine and schizophrenia: An analysis of the theory
Carlton, P. L., & Manowitz, P. (1984) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(84)90029-0 · Cited by 48
Neonatal levels of acute phase proteins and later risk of non-affective psychosis
Gardner, R. M., Dalman, C., Wicks, S., Lee, B. K., & Karlsson, H. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.5 · Cited by 48
Flagged first, then by citations
Research works printed but not linked: 1
- [32]World Health Organization SCAN: Schedules for Clinical Assessment in Neuropsychiatry, Version 2.0 1994 Psychiatric Publishers International/American Psychiatric Press Inc Geneva, Switzerland
Cited by
Sorted by citations
Otte, C., Gold, S. M., Penninx, B. W., Pariante, C. M., Etkin, A., Fava, M., Mohr, D. C., & Schatzberg, A. F. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.65 · Cited by 2,269
Kandola, A., Ashdown-Franks, G., Hendrikse, J., Sabiston, C. M., & Stubbs, B. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.09.040 · Cited by 1,309
Haapakoski, R., Mathieu, J., Ebmeier, K. P., Alenius, H., & Kivimäki, M. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.06.001 · Cited by 1,129
Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa
Dantzer, R. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2016 · Cited by 1,073
Osimo, E. F., Pillinger, T., Rodriguez, I. M., Khandaker, G. M., Pariante, C. M., & Howes, O. D. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.02.010 · Cited by 937
Self-citation
Metadata
- Authors
- Khandaker, G. M., Pearson, R. M., Zammit, S., Lewis, G., & Jones, P. B.
- Affiliations
- National Health Service (GB)
- University of Bristol (GB)
- Corresponding author
- Khandaker, Golam M.
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2014-10-01
- Volume
- 71
- Issue
- 10
- Pages
- 1121
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC4561502
- OpenAlex
- W2134549690
- Cited by
- 846
- References
- 45
- Citations by year
- 2026: 85 · 2025: 66 · 2024: 75 · 2023: 81 · 2022: 72 · 2021: 102 · 2020: 100 · 2019: 70 · 2018: 52 · 2017: 57 · 2016: 48 · 2015: 35 · 2014: 3
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Wellcome Trust (088869/Z/09/Z, 095844/Z/11/Z, 102215, 092731, 095844, 084268/Z/07/Z)
- National Institute for Health and Care Research (RP-PG-0606-1335)
- Medical Research Council (MR/L010305/1, MC_PC_15018)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- interleukin-6, C-reactive protein, depression, psychosis, psychotic experiences, inflammatory markers, early adulthood, Avon Longitudinal Study of Parents and Children, dose-response relationship, postpartum depression, psychiatric comorbidity, cardiovascular comorbidity, diabetes comorbidity, first-episode psychosis, psychotic relapse
- MeSH terms
- Adolescent, C-Reactive Protein, Child, Depression, England, Female, Humans, Interview, Psychological, Male, Prospective Studies, Psychiatric Status Rating Scales, Psychotic Disorders, Risk Factors, Biomarkers, Interleukin-6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
