Longitudinal population subgroups of CRP and risk of depression in the ALSPAC birth cohort
Open accessAbstract
BACKGROUND: Meta-analyses confirm increased circulating C-reactive protein (CRP) levels in depression. Longitudinal studies have linked one-off measurements of CRP at baseline with increased risk of developing depressive symptoms subsequently at follow-up, but studies with repeat CRP measures from the same individuals are scarce. METHODS: We have examined whether longitudinal patterns of inflammation, based on three CRP measurements from childhood to early-adulthood, are associated with the risk of depression in early-adulthood in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort. RESULTS: Using Gaussian mixture modelling of available CRP data from age 9, 15 and 18 years, we identified four population clusters/sub-groups reflecting different longitudinal patterns of CRP: persistently low (N=463, 29.5%); persistently high (N=371, 24%); decreasing (N=360, 23%); increasing (N=367, 23.5%). The increasing group showed a steep increase in CRP levels between adolescence and early-adulthood. Participants in this group had a higher risk of moderate/severe depression at age 18 years, compared with those with persistently low CRP; adjusted odds ratio (OR)=3.78 (95% Confidence Interval (CI), 1.46-9.81; p=0.006). The odds of moderate/severe depression were also increased for the persistently high CRP group, but this was not statistically significant; OR=2.54 (95% CI, 0.90-7.16). LIMITATIONS: Repeat CRP measures were available for a subset, who may not be representative of all cohort participants. CONCLUSIONS: The results suggest that an increasing pattern of inflammation from adolescence to early-adulthood is associated with risk of depression in early-adulthood.
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
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?
In 1561 participants, subjects who displayed a pattern of increasing CRP levels from childhood to early adulthood had a higher risk of moderate/severe depression at 18 years, compared to those who had persistently low CRP levels.
“A UK general population-based birth cohort study, named the Avon Longitudinal Study of Parents and Children (ALSPAC), evaluating CRP levels in 1561 participants, identified population sub-groups of young people characterized by different longitudinal patterns of CRP levels. Subjects who displayed a pattern of increasing CRP levels from childhood to early adulthood had a higher risk of moderate/se”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [29]
Subjects who displayed persistently elevated CRP levels also had increased ORs of moderate/severe depression at 18 years, even though this association was not statistically significant.
“Subjects who displayed persistently elevated CRP levels also had increased ORs of moderate/severe depression at 18 years, even though this association was not statistically significant.”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [29]
Overall, an increase in low-grade inflammatory levels from childhood to early adulthood is strongly associated with the risk of developing depression in early adulthood.
“Overall, an increase in low-grade inflammatory levels from childhood to early adulthood is strongly associated with the risk of developing depression in early adulthood [29].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Modern Applied Statistics with S
Venables, W., & Ripley, B. (2010) · Statisctics and computing/Statistics and computing · doi:10.1007/978-0-387-21706-2 · Cited by 16,188 · see citing works
ggplot2: Elegant Graphics for Data Analysis
Wickham, H. (2009) · doi:10.1007/978-0-387-98141-3 · Cited by 14,447 · see citing works
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,501 · see citing works
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 · see citing works
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 · see citing works
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729 · see citing works
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009 · see citing works
Boyd, A., Golding, J., Macleod, J., Lawlor, D. A., Fraser, A., Henderson, J., Molloy, L., Ness, A., Ring, S., & Davey Smith, G. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dys064 · Cited by 2,996 · see citing works
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 · see citing works
mclust 5: Clustering, Classification and Density Estimation Using Gaussian Finite Mixture Models
Scrucca, L., Fop, M., Murphy, T. B., & Adrian, E. R. (2016) · The R Journal · doi:10.32614/rj-2016-021 · Cited by 2,914 · see citing works
The Split-Apply-Combine Strategy for Data Analysis
Wickham, H. (2011) · Journal of Statistical Software · doi:10.18637/jss.v040.i01 · Cited by 2,901 · see citing works
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 · see citing works
Elevated C-reactive protein levels in overweight and obese adults
Visser, M. (1999) · JAMA · doi:10.1001/jama.282.22.2131 · Cited by 2,494 · see citing works
Cohort Profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort
Fraser, A., Macdonald-Wallis, C., Tilling, K., Boyd, A., Golding, J., Davey Smith, G., Henderson, J., Macleod, J., Molloy, L., Ness, A., et al. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dys066 · Cited by 2,494 · see citing works
Modern Applied Statistics with S,
Kemp, F. (2003) · Journal of the Royal Statistical Society Series D (The Statistician) · doi:10.1046/j.1467-9884.2003.t01-19-00383_22.x · Cited by 2,321 · see citing works
Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses
Danesh, J. (2000) · BMJ · doi:10.1136/bmj.321.7255.199 · Cited by 1,692 · see citing works
Goldsmith, D. R., Rapaport, M. H., & Miller, B. J. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.3 · Cited by 1,683 · see citing works
Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.4 · Cited by 1,617 · see citing works
Lewis, G., Pelosi, A. J., Araya, R., & Dunn, G. (1992) · Psychological Medicine · doi:10.1017/s0033291700030415 · Cited by 1,487 · see citing works
Self-citationHaapakoski, 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 · see citing works
Prevalence and incidence studies of anxiety disorders: A systematic review of the literature
Somers, J. M., Goldner, E. M., Waraich, P., & Hsu, L. (2006) · The Canadian Journal of Psychiatry · doi:10.1177/070674370605100206 · Cited by 1,114 · see citing works
CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies.
Valkanova, V., Ebmeier, K. P., & Allan, C. L. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.06.004 · Cited by 972 · see citing works
Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment
Khandaker, G. M., Cousins, L., Deakin, J., Lennox, B. R., Yolken, R., & Jones, P. B. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(14)00122-9 · Cited by 926 · see citing works
Self-citationRuhé, H. G., Mason, N. S., & Schene, A. H. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001949 · Cited by 861 · see citing works
Khandaker, G. M., Pearson, R. M., Zammit, S., Lewis, G., & Jones, P. B. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1332 · Cited by 846 · see citing works
Self-citationLeonard, B., & Maes, M. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.12.005 · Cited by 805 · see citing works
Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., & Critchley, H. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.015 · Cited by 756 · see citing works
Kappelmann, N., Lewis, G., Dantzer, R., Jones, P. B., & Khandaker, G. M. (2018) · Molecular Psychiatry · doi:10.1038/mp.2016.167 · Cited by 659 · see citing works
Self-citationGimeno, 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 · see citing works
Prevalence and Incidence Studies of Mood Disorders: A Systematic Review of the Literature
Waraich, P., Goldner, E. M., Somers, J. M., & Hsu, L. (2004) · The Canadian Journal of Psychiatry · doi:10.1177/070674370404900208 · Cited by 522 · cited 2× · see citing works
“Depression and other mood disorders are common in all poplations [1], and a quarter of all cases emerge before 20 years of ge [2,3].”
BackgroundElevated 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 · see citing works
Jenkins, R., Lewis, G., Bebbington, P., Brugha, T. S., Farrell, M., GILL, B., & Meltzer, H. (1997) · Psychological Medicine · doi:10.1017/s0033291797005308 · Cited by 430 · see citing works
Self-citationvon Känel, R., Hepp, U., Kraemer, B., Traber, R., Keel, M., Mica, L., & Schnyder, U. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.06.009 · Cited by 408 · see citing works
Fernandes, B. S., Steiner, J., Bernstein, H.-G., Dodd, S., Pasco, J. A., Dean, O. M., Nardin, P., Gonçalves, C.-A., & Berk, M. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.87 · Cited by 348 · see citing works
Association of high-sensitivity C-reactive protein with <i>de novo</i> major depression
Pasco, J. A., Nicholson, G. C., Williams, L. J., Jacka, F. N., Henry, M. J., Kotowicz, M. A., Schneider, H. G., Leonard, B. E., & Berk, M. (2010) · British Journal of Psychiatry · doi:10.1192/bjp.bp.109.076430 · Cited by 321 · see citing works
Khandaker, G. M., Zuber, V., Rees, J. M. B., Carvalho, L. A., Mason, A. M., Foley, C. N., Gkatzionis, A., Jones, P. B., & Burgess, S. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0395-3 · Cited by 279 · see citing works
Self-citationCumulative Depression Episodes Predict Later C-Reactive Protein Levels: A Prospective Analysis
Copeland, W. E., Shanahan, L., Worthman, C., Angold, A., & Costello, E. J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.09.023 · Cited by 265 · see citing works
Genetic Contributions of Inflammation to Depression
Barnes, J., Mondelli, V., & Pariante, C. M. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.169 · Cited by 237 · see citing works
Immunopsychiatry: important facts
Khandaker, G. M., Dantzer, R., & Jones, P. B. (2017) · Psychological Medicine · doi:10.1017/s0033291717000745 · Cited by 200 · see citing works
Self-citationLow-grade inflammation predicts persistence of depressive symptoms
Zalli, A., Jovanova, O., Hoogendijk, W. J. G., Tiemeier, H. W., & Carvalho, L. A. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3919-9 · Cited by 193 · see citing works
Assessing psychiatric disorder with a human interviewer or a computer.
Lewis, G. (1994) · Journal of Epidemiology & Community Health · doi:10.1136/jech.48.2.207 · Cited by 151 · see citing works
Self-citationReview of Three Latent Class Cluster Analysis Packages: Latent Gold, poLCA, and MCLUST
Haughton, D., Legrand, P., & Woolford, S. (2009) · The American Statistician · doi:10.1198/tast.2009.0016 · Cited by 139 · see citing works
Khandaker, G. M., Zuber, V., Rees, J. M. B., Carvalho, L. A., Mason, A. M., Foley, C. N., Gkatzionis, A., Jones, P. B., & Burgess, S. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0857-7 · Cited by 139 · see citing works
Self-citationJenkins, R., Lewis, G., Bebbington, P., Brugha, T. S., Farrell, M., Gill, B., & Meltzer, H. (2003) · International Review of Psychiatry · doi:10.1080/0954026021000045921 · Cited by 125 · see citing works
Self-citationMetcalf, S. A., Jones, P. B., Nordström, T., Timonen, M., Mäki, P. H., Miettunen, J., Jääskeläinen, E., Järvelin, M., Štochl, J., Murray, G. K., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.09.008 · Cited by 124 · see citing works
Self-citationKhandaker, G. M., Zammit, S., Burgess, S., Lewis, G., & Jones, P. B. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.11.020 · Cited by 118 · see citing works
Self-citationKnudsen, 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 · see citing works
Khandaker, G. M., Štochl, J., Zammit, S., Goodyer, I. M., Lewis, G., & Jones, P. B. (2017) · Psychological Medicine · doi:10.1017/s0033291717003038 · Cited by 67 · see citing works
Self-citationSpiers, N. A., Bebbington, P., McManus, S., Brugha, T. S., Jenkins, R., & Meltzer, H. (2011) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.110.084269 · Cited by 49 · see citing works
Kappelmann, N., Khandaker, G. M., Dal, H., Štochl, J., Kosidou, K., Jones, P. B., Dalman, C., & Karlsson, H. (2018) · Psychological Medicine · doi:10.1017/s0033291718000831 · Cited by 33 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
C-Reactive protein as a biomarker for major depressive disorder?
Orsolini, L., Pompili, S., Tempia Valenta, S., Salvi, V., & Volpe, U. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031616 · Cited by 171 · see citing works
Eccles, J. A., Quadt, L., McCarthy, H., Davies, K. A., Bond, R., David, A. S., Harrison, N. A., & Critchley, H. D. (2022) · BMJ Open · doi:10.1136/bmjopen-2022-066130 · Cited by 20 · see citing works
- Authors
- Osimo, E. F., Stochl, J., Zammit, S., Lewis, G., Jones, P. B., & Khandaker, G. M.
- Affiliations
- University of Cambridge (GB)
- University College London (GB)
- Corresponding author
- Osimo, Emanuele F.
- Venue
- Comprehensive Psychiatry
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 96
- Pages
- 152143
- ISSN
- 0010-440X (ISSN-L)
- PMC
- PMC6945112
- OpenAlex
- W2984556316
- Cited by
- 30
- References
- 51
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 3
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Comprehensive Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Medical Research Council
- MQ: Transforming Mental Health
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- C-reactive protein, depression, inflammation, subpopulations, childhood to early adulthood, adolescence, ALSPAC birth cohort
- MeSH terms
- Adolescent, Adult, C-Reactive Protein, Child, Depression, Depressive Disorder, Female, Humans, Longitudinal Studies, Male, Prospective Studies, Risk, Cohort Studies
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
