The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Association between a functional interleukin 6 receptor genetic variant and risk of depression and psychosis in a population-based birth cohort
Open accessAbstract
OBJECTIVE: Interleukin 6 (IL-6) levels are commonly elevated in patients with depression and psychosis and in people who are at risk of developing these disorders. A common, functional variant in the IL6R gene (IL6R Asp358Ala; rs2228145 A > C) is known to dampen down inflammation by impairing IL6R signaling. We have examined the association of Asp358Ala with diagnosis of depression and psychosis, serum IL-6, CRP levels, and a number of risk factors commonly linked with inflammation, depression or psychosis. We predicted that if IL-6 were related to depression/psychosis risk causally, rather than due to confounding, Asp358Ala would be associated with risk of these disorders, serum IL-6, CRP levels, but not with any of the confounders. METHOD: We used data from the population-based ALSPAC birth cohort. Serum IL-6 and CRP levels were measured at age 9 years. Psychotic disorder, ICD-10 diagnosis of severe depressive episode, and total depression score were assessed at age 18 years. IL6R Asp358Ala was genotyped using the Illumina HumanHap550 quad genome-wide SNP genotyping platform. Risk factors assessed include sex, body mass index, social class, ethnicity, maternal education, birth weight, gestational age, maternal post-natal depression, childhood psychological and behavioral problems, and total IQ score. RESULTS: ), consistent with an anti-inflammatory effect downstream of IL-6. Asp358Ala was not associated with total depression score. Asp358Ala was not associated with any of the other risk factors commonly linked with inflammation, depression or psychosis (all P > 0.20). CONCLUSIONS: The findings provide further evidence that the IL-6/IL6R pathways are involved in pathogenesis of severe depression and psychosis, and may be novel therapeutic targets. Previously reported associations between IL-6, depression and psychosis are unlikely to be fully explained by confounding. Based on a small number of cases, findings from the current study need replication in other samples.
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
Figures
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?
In the citing paper
“Variants in the IL6R gene have been found to be associated with increased risk of coronary artery disease24, rheumatoid arthritis, atrial fibrillation, and abdominal aortic aneurysm, and with increased susceptibility to asthma, type 1 diabetes, and depression36,37.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [36]
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
Diagnostic and Statistical Manual of Mental Disorders
(2012) · Springer eBooks · doi:10.1007/springerreference_121117 · Cited by 20,772
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
Detection of Postnatal Depression: Development of the 10-item Edinburgh Postnatal Depression Scale
Cox, J. L., Holden, J. M., & Sagovsky, R. (1987) · British Journal of Psychiatry · doi:10.1192/bjp.150.6.782 · Cited by 14,183 · cited 1×
“Mother’s postnatal depression was measured by the self-report Edinburgh Postnatal Depression Scale administered at 8 weeks postpartum (Cox et al., 1987).”
MethodMolecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577
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
Davey Smith, G., & Ebrahim, S. (2003) · International Journal of Epidemiology · doi:10.1093/ije/dyg070 · Cited by 5,882
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
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 · cited 1×
“, 2008), diabetes mellitus (Pradhan et al., 2001), depression and psychosis (Khandaker et al.”
Background
Research works printed but not linked: 1
- Wechsler, D., Golombok, S., Rust, J., 1992. Weschler Intelligence Scale for Children (3rd Edition) (WISC–III UK). The Psychological Corporation.
Cited by
Sorted by citations
Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690
Role of Interleukin-6 in Depressive Disorder
Ting, E. Y.-C., Yang, A. C., & Tsai, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062194 · Cited by 404
“indicated that a common functional variant in the IL6R gene (IL6R Asp358Ala; rs2228145 A > C), which is able to decrease inflammation by impairing IL-6R signaling, is associated with depression risk [99].”
BackgroundImmune targets for therapeutic development in depression: towards precision medicine
Drevets, W. C., Wittenberg, G. M., Bullmore, E. T., & Manji, H. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00368-1 · Cited by 348
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 287
Self-citationCytokine Alterations in Schizophrenia: An Updated Review
Momtazmanesh, S., Zare-Shahabadi, A., & Rezaei, N. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00892 · Cited by 277
“in 2018, finding a strong association between a genetic variant of IL-6 receptor relating to the levels of IL-6 and CRP and development of schizophrenia (119).”
BackgroundThe microbiota-immune axis as a central mediator of gut-brain communication
Fung, T. C. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104714 · Cited by 234
Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia
Upthegrove, R., & Khandaker, G. M. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2018_88 · Cited by 230
Self-citationKhandaker, 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
Self-citationChu, A. L., Štochl, J., Lewis, G., Zammit, S., Jones, P. B., & Khandaker, G. M. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.11.007 · Cited by 136
Self-citationPeripheral blood cellular immunophenotype in depression: a systematic review and meta-analysis
Foley, É. M., Parkinson, J. T., Mitchell, R. E., Turner, L., & Khandaker, G. M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01919-7 · Cited by 138
Self-citationKern, C., Wan, J., LeWinn, K. Z., Ramirez, F. D., Lee, Y., McCulloch, C. E., Langan, S. M., & Abuabara, K. (2021) · JAMA Dermatology · doi:10.1001/jamadermatol.2021.2657 · Cited by 103
“In cross-sectional analyses, we did not find associations between IL-6 and AD or symptoms of depression (as measured by the SMFQ) at age nine years, nor with CRP at ages 9, 14 and 16 years.”
InfluentialInflammation and depression in young people: a systematic review and proposed inflammatory pathways
Toenders, Y. J., Laskaris, L., Davey, C. G., Berk, M., Milaneschi, Y., Lamers, F., Penninx, B. W. J. H., & Schmaal, L. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01306-8 · Cited by 106
Perry, B. I., Burgess, S., Jones, H. J., Zammit, S., Upthegrove, R., Mason, A. M., Day, F. R., Langenberg, C., Wareham, N. J., Jones, P. B., et al. (2021) · PLoS Medicine · doi:10.1371/journal.pmed.1003455 · Cited by 91
Self-citationKitzbichler, M. G., Aruldass, A. R., Barker, G. J., Wood, T., Dowell, N. G., Hurley, S. A., McLean, J., Correia, M., Clarke, C., Pointon, L. J., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01272-1 · Cited by 93
“…patients therapeutically administered the pro-inflammatory cytokine interferon-α (Musselman et al., 2001), longitudinal epidemiological studies (Khandaker et al., 2018, 2014; Wium-Andersen et al., 2013; Liukkonen et al., 2006), investigations of co-morbid depression in systemic inflammatory…”
BackgroundImpaired regulatory T cell control of astroglial overdrive and microglial pruning in schizophrenia
Zuelli, F. M. D. G. C., & Deakin, J. F. W. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.03.004 · Cited by 90
Brunoni, A. R., Suen, P. J. C., Bacchi, P. S., Razza, L. B., Klein, I., dos Santos, L. A., Santos, I. S., Valiengo, L. D. C. L., Neto, J. G., Moreno, M., et al. (2021) · Psychological Medicine · doi:10.1017/s0033291721001719 · Cited by 90
Pandurangi, A. K., & Buckley, P. F. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2019_91 · Cited by 76
Khandaker, G. M., Oltean, B. P., Kaşer, M., Dibben, C. R. M., Ramana, R., Jadon, D. R., Dantzer, R., Coles, A. J., Lewis, G., & Jones, P. B. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-025333 · Cited by 74
Self-citationEvaluating the Hypothesis That Schizophrenia Is an Inflammatory Disorder
Miller, B. J., & Goldsmith, D. R. (2020) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20200015 · Cited by 73
Inflammatory biomarkers in schizophrenia: Implications for heterogeneity and neurobiology
Miller, B. J., & Goldsmith, D. R. (2019) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2019.100006 · Cited by 72
Parisinos, C. A., Serghiou, S., Katsoulis, M., George, M. J., Patel, R. S., Hemingway, H., & Hingorani, A. D. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.05.022 · Cited by 67
Gromark, C., Harris, R. A., Wickström, R., Horne, A., Silverberg-Mörse, M., Serlachius, E., & Mataix‐Cols, D. (2019) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2018.0127 · Cited by 68
“Furthermore, inflammatory markers such as CRP, IL-6, and TNF-a have been associated with development or severity of psychiatric disorders such as depression, psychosis, andbipolar disorder (Najjar et al. 2013; Goldstein et al. 2015; Khandaker et al. 2018a, 2018b).”
Dysglycaemia, Inflammation and Psychosis: Findings From the UK ALSPAC Birth Cohort
Perry, B. I., Upthegrove, R., Thompson, A. D., Marwaha, S., Zammit, S., Singh, S. P., & Khandaker, G. M. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby040 · Cited by 55
Self-citationPrenatal and childhood adverse life events, inflammation and depressive symptoms across adolescence
Flouri, E., Francesconi, M., Midouhas, E., & Lewis, G. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.09.024 · Cited by 58
Self-citationČierniková, S., Mego, M., & Chovanec, M. (2021) · Cancers · doi:10.3390/cancers13040782 · Cited by 55
Benros, M. E., & Mortensen, P. B. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2019_93 · Cited by 53
Parkinson, J. T., Foley, É. M., Jadon, D. R., & Khandaker, G. M. (2020) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x20970028 · Cited by 52
Self-citationPaternal transgenerational epigenetic mechanisms mediating stress phenotypes of offspring
Cunningham, A. M., Walker, D. M., & Nestler, E. J. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14582 · Cited by 50
Perry, B. I., Zammit, S., Jones, P. B., & Khandaker, G. M. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2021.02.008 · Cited by 49
Self-citationA longitudinal analysis of cytokines in anorexia nervosa
Dalton, B., Leppänen, J., Campbell, I. C., Chung, R., Breen, G. D., Schmidt, U. H., & Himmerich, H. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.05.012 · Cited by 43
Perry, B. I., Khandaker, G. M., Marwaha, S., Thompson, A., Zammit, S., Singh, S. P., & Upthegrove, R. (2020) · Psychological Medicine · doi:10.1017/s0033291719000308 · Cited by 42
Self-citationHafiane, A., & Daskalopoulou, S. S. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106157 · Cited by 41
Russell, A. E., Ford, T., Gunnell, D., Heron, J., Joinson, C., Moran, P., Relton, C., Suderman, M., Hemani, G., & Mars, B. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.05.065 · Cited by 39
“Similar methods have been used to study the association between inflammation and other psychiatric outcomes such as schizophrenia and depression (Hartwig et al., 2017; Prins et al., 2016; Khandaker et al., 2018).”
MethodMonocyte count in schizophrenia and related disorders: a systematic review and meta-analysis
Mazza, M. G., Capellazzi, M., Lucchi, S., Tagliabue, I., Rossetti, A., & Clerici, M. (2020) · Acta Neuropsychiatrica · doi:10.1017/neu.2020.12 · Cited by 39
“Moreover, variants of cytokines receptor genes seem to be involved in the pathogenesis of more severe psychosis (Khandaker et al., 2018).”
BackgroundSlaney, C., Sallis, H., Jones, H. J., Dardani, C., CHARGE Inflammation Working Group, Tilling, K. M., Munafo, M. R., Smith, G. D., Mahedy, L., & Khandaker, G. M. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.02.010 · Cited by 39
“One promising intervention target could be inflammation (Khandaker et al., 2018).”
Self-citationClinical phenotypes of depressed patients with evidence of inflammation and somatic symptoms
Foley, É. M., Parkinson, J. T., Kappelmann, N., & Khandaker, G. M. (2021) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2021.100079 · Cited by 34
Self-citationFlouri, E., Francesconi, M., Papachristou, E., Midouhas, E., & Lewis, G. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.02.023 · Cited by 37
Self-citationKappelmann, 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
Self-citationLongitudinal population subgroups of CRP and risk of depression in the ALSPAC birth cohort
Osimo, E. F., Stochl, J., Zammit, S., Lewis, G., Jones, P. B., & Khandaker, G. M. (2020) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2019.152143 · Cited by 30
Self-citationLevy, A., Taïb, S., Arbus, C., Péran, P., Sauvaget, A., Schmitt, L., & Yrondi, A. (2019) · Journal of Ect · doi:10.1097/yct.0000000000000570 · Cited by 32
Galan, D., Perry, B. I., Warrier, V., Davidson, C. C., Stupart, O., Easton, D. F., Khandaker, G. M., & Murray, G. K. (2022) · Scientific Reports · doi:10.1038/s41598-022-19214-4 · Cited by 34
Self-citationMiller, B. J., Herzig, K., Jokelainen, J. J., Karhu, T., Keinanen-Kiukaanniemi, S. M., Järvelin, M., Veijola, J. M., Viinamäki, H. T., Tanskanen, P., Jääskeläinen, E., et al. (2020) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-020-01134-x · Cited by 31
Osimo, E. F., Perry, B. I., Cardinal, R. N., Lynall, M.-E., Lewis, J. R., Kudchadkar, A., Murray, G. K., Pérez, J., Jones, P. B., & Khandaker, G. M. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.09.011 · Cited by 31
Self-citationGordillo‐Marañón, M., Zwierzyna, M., Charoen, P., Drenos, F., Chopade, S., Shah, T., Engmann, J., Casas, J. P., Chaturvedi, N., Papacosta, O., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25731-z · Cited by 32
IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk
Zhang, L., Omarov, M., Xu, L., deGoma, E. M., Natarajan, P., & Georgakis, M. K. (2025) · Nature Cardiovascular Research · doi:10.1038/s44161-025-00700-7 · Cited by 32
“The effect on depression is in line with previous analyses of IL6R genetic instruments 63,64 , as well as reports on tocilizumab in patients with rheumatoid arthritis 65 .”
Microbial metabolites and immune regulation: New targets for major depressive disorder
Merchak, A. R., & Gaultier, A. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100169 · Cited by 30
Unravelling the broader complexity of IL-6 involvement in health and disease
Jenkins, R. L., Hughes, S. T. O., Figueras, A. C., & Jones, S. A. (2021) · Cytokine · doi:10.1016/j.cyto.2021.155684 · Cited by 25
“Genetic studies further identify various risk alleles in IL6 and IL6R associated with major depressive disorders 221-226 .”
Викторовна, М. Е., Vyalova, N. M., Ermakov, E. A., Levchuk, L. A., Simutkin, G. G., Bokhan, N. A., & Ivanova, S. А. (2023) · Genes · doi:10.3390/genes14071460 · Cited by 26
“(2018) [47] IL6R: rs2228145 (Asp358Ala) 9912 unselected participants from the ALSPAC birth cohort Asp358Ala was associated with a reduced risk of severe depression and/or psychosis.”
BackgroundBedeutung von psychosozialen Faktoren in der Kardiologie – Update 2024
Kindermann, I., Köllner, V., Albus, C., Boer, J., Dannberg, G., Fritzsche, K., Gunold, H., Herrmann‐Lingen, C., Leithäuser, B., Meesmann, M., et al. (2024) · Die Kardiologie · doi:10.1007/s12181-024-00708-6 · Cited by 30
Brunoni, A. R., Salum, G. A., Hoffmann, M. S., Goulart, A. C., Barreto, S. M., Canhada, S., Carvalho, A. F., Koyanagi, A., Cálice-Silva, V., Lotufo, P. A., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.074 · Cited by 22
Prenatal and Childhood Immuno-Metabolic Risk Factors for Adult Depression and Psychosis
Kappelmann, N., Perry, B. I., & Khandaker, G. M. (2022) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000322 · Cited by 22
Self-citationFoley, É. M., Griffiths, S. L., Murray, A., Rogers, J. C., Zuelli, F. M. D. G. C., Hickinbotham, H., Warwick, E., Wilson, M., Kaşer, M., Murray, G. K., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2022-067944 · Cited by 25
Self-citationGüngör, B. B., Akgul, A. I., Taymur, İ., Demirci, H., & İnel, A. (2020) · Psychiatria Danubina · doi:10.24869/psyd.2020.105 · Cited by 21
New approaches in psychiatric drug development
van der Doef, T. F., Domingo, S. Z., Jacobs, G. E., Drevets, W. C., Marston, H. M., Nathan, P. J., Tome, M. B., Tamminga, C. A., van Gerven, J., & Kas, M. J. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.06.006 · Cited by 18
Yamasaki, K., Hasegawa, T., & Takeda, M. (2020) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12100 · Cited by 19
Immunity and psychiatric disorders: variabilities of immunity biomarkers are they specific?
Dubois, T., Reynaert, C., Jacques, D., Lepièce, B., Patigny, P., & Zdanowicz, N. (2018) · PubMed · Cited by 17
C-Reactive Protein (CRP): A Potent Inflammation Biomarker in Psychiatric Disorders
Orsolini, L., Pompili, S., & Volpe, U. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-19-7376-5_7 · Cited by 19
Herniman, S. E., Wood, S. J., Khandaker, G. M., Dazzan, P., Pariante, C. M., Barnes, N. M., Krynicki, C. R., Nikkheslat, N., Vincent, R. C., Roberts, A., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02570-8 · Cited by 17
“In addition to the reliable edge weights of interest (reported above), accuracy and stability analyses also revealed adequate CS-coef fi cients, ranging between 0.36 and 0.67 (See Supplementary).”
InfluentialSelf-citationENĂTESCU, V. R. (2020) · FARMACIA · doi:10.31925/farmacia.2020.3.14 · Cited by 16
“Several studies have repeatedly detected that higher levels of pro-inflammatory markers such as CRP and interleukin 6 (IL-6) were associated with an increased likelihood of the development of depression [5-7].”
BackgroundSolmi, F., Bulik, C. M., Stavola, B. L. D., Dalman, C., Khandaker, G. M., & Lewis, G. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.07.040 · Cited by 15
Self-citationGenomic-Analysis-Oriented Drug Repurposing in the Search for Novel Antidepressants
Lesmana, M. H. S., Le, N. Q. K., Chiu, W., Chung, K., Wang, C., Irham, L. M., & Chung, M. (2022) · Biomedicines · doi:10.3390/biomedicines10081947 · Cited by 15
“Furthermore, the upregulation and downregulation of IL6 and CRP affect depression severity [70,73].”
BackgroundKittel‐Schneider, S., Kaspar, M., Berliner, D., Weber, H., Deckert, J., Ertl, G., Störk, S., Angermann, C. E., & Reif, A. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.04.002 · Cited by 13
Castillo-Ávila, R. G., Mendoza, A. D. G., Juárez‐Rojop, I. E., López‐Narváez, M. L., Dionisio-García, D. M., Nolasco-Rosales, G. A., Ramos-Méndez, M. Á., Hernández‐Díaz, Y., Tovilla‐Zárate, C. A., González‐Castro, T. B., et al. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192214735 · Cited by 14
“This gene is known to regulate IL-6 bioactivity; one of the most implicated variants with a direct effect on the expression of the IL6R gene is the Asp358Ala, rs2228145 A > C (formerly known as rs8192284) [26,49].”
BackgroundInfluentialSpanoudaki, M., Papadopoulou, S. Κ., Antasouras, G., Papadopoulos, K., Psara, E., Vorvolakos, T., Solovos, E., Chrysafi, M., Psallas, M., Mentzelou, M., et al. (2024) · Life · doi:10.3390/life14040479 · Cited by 16
Ferreira, N. V., Gonçalves, N. G., Khandpur, N., Steele, E. M., Levy, R. B., Monteiro, C. A., Goulart, A. C., Brunoni, A. R., Bacchi, P. S., Lotufo, P. A., et al. (2024) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2024.10.012 · Cited by 14
Kang, Y., Shin, D., Kim, A., Tae, W., Ham, B., & Han, K. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.11.017 · Cited by 15
Khandaker, G. M. (2019) · International Journal of Epidemiology · doi:10.1093/ije/dyz201 · Cited by 13
Self-citationInflammatory Markers and Episodic Memory Functioning in Depressive Disorders
Wachowska, K., Szemraj, J., Śmigielski, J., & Gałecki, P. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11030693 · Cited by 13
“It has also been suggested in longitudinal studies that elevated levels of interleukins might precede mental disorders [19,20] and are associated with certain genetic variants [21].”
BackgroundMarco, R. D., Barritt, A. W., Cercignani, M., Cabbai, G., Colasanti, A., & Harrison, N. A. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.04.010 · Cited by 15
Liu, M., Fan, G., Meng, L., Yang, K., & Liu, H. (2024) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2300343 · Cited by 10
Khantakova, J. N., Bondar, N. P., Antontseva, E. V., & Reshetnikov, V. V. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.1066794 · Cited by 10
“Children with elevated levels of IL-6 and C-reactive protein at 9 years of age are at a higher risk of depression onset by 18 years of age (Khandaker et al., 2018).”
BackgroundWang, Y., Meagher, R. B., Ambati, S., Ma, P., & Phillips, B. G. (2020) · Sleep And Breathing · doi:10.1007/s11325-020-02205-y · Cited by 9
Kitzbichler, M. G., Aruldass, A. R., Barker, G. J., Wood, T., Dowell, N. G., Hurley, S. A., McLean, J., Correia, M., Clarke, C., Pointon, L. J., et al. (2020) · medRxiv · doi:10.1101/2020.09.09.20191262 · Cited by 9
Sub-clinical systemic inflammation as a determinant of admission duration in psychosis
Blackman, G., DeLaney, J., MacCabe, J. H., Khandaker, G. M., & McGuire, P. K. (2025) · Schizophrenia Research · doi:10.1016/j.schres.2024.12.010 · Cited by 9
“There is growing evidence that immune dysfunction plays a significant role in the pathophysiology of psychotic disorders (Miller et al., 2011; Khandaker et al., 2014; Khandaker et al., 2018).”
Self-citationMonitoring inflammation in psychiatry: Caveats and advice
Khalfallah, O., Barbosa, S., Martinuzzi, E., Davidovic, L., Yolken, R. H., & Glaichenhaus, N. (2021) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.09.003 · Cited by 8
Mendelian randomization study on the effect of tumor necrosis factor on schizophrenia
Ma, N., & Wang, R. (2022) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000329 · Cited by 8
Inflammatory pathology in depression and suicide: a mechanistic distillation of clinical correlates
Costanza, A., Amerio, A., Aguglia, A., Magnani, L., Parise, A., Nguyen, K. D., Berardelli, I., Pompili, M., Amore, M., & Serafini, G. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1479471 · Cited by 7
Binić, I., Petrovic, J., Žikić, O., Tošić-Golubović, S., Djordjevic, V., Stevanovic, M., Krtinić, D., & Apostolovic, M. A. (2025) · Brain Sciences · doi:10.3390/brainsci15090932 · Cited by 6
“Carefully selected participants—non-smokers, without obesity, somatic or metabolic comorbidities—enabled the minimisation of known modulators of peripheral IL-6 levels [20,33].”
Primak, A. L., Дмитриевич, Б. К., Rubina, K. A., Станиславович, Д. С., Neyfeld, E. A., Illarionova, M. E., Semina, E. V., Sheleg, D., Va, T., & Karagyaur, M. N. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1361764 · Cited by 7
Francesconi, M., Minichino, A., Khandaker, G. M., Midouhas, E., Lewis, G., & Flouri, E. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.07.035 · Cited by 6
Self-citationGordillo‐Marañón, M., Zwierzyna, M., Charoen, P., Drenos, F., Chopade, S., Shah, T., Engmann, J., Casas, J. P., Chaturvedi, N., Papacosta, O., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.11.377747 · Cited by 6
Petrillo, A. D., Favale, A., Onali, S., Kumar, A., Abbracciavento, G., & Fantini, M. C. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14155522 · Cited by 7
“In a Mendelian randomization study involving candidate genes, a functional SNP in the IL-6 receptor promoter was identified, providing estimates of CRP, IL-6, and the severity of depression symptoms in a population cohort study [31].”
Gut Microbes: The Gut Brain Connection
Lynch, C. M. K., O’Riordan, K. J., Clarke, G. A., & Cryan, J. F. (2023) · Springer eBooks · doi:10.1007/978-3-031-46712-7_4 · Cited by 5
Potential links between brown adipose tissue, circadian dysregulation, and suicide risk
Sarlon, J., Partonen, T., & Lang, U. E. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1196029 · Cited by 5
“IL-6 is involved in the physiological homeostasis of neural tissue and in neuropsychiatric disorders (Rothaug et al., 2016; Khandaker et al., 2018).”
BackgroundDardani, C., Yarmolinsky, J., Robinson, J. W., Zheng, J., Smith, G. D., Lewis, S. J., & Sinclair, L. I. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/712133 · Cited by 5
Rees, K., Aicheler, R., Butcher, L., Dodd, A., Geen, J., Lynch, C., Massey, I., Morris, K., Tennant, B. P., & Webb, R. (2025) · Cytokine · doi:10.1016/j.cyto.2025.156884 · Cited by 4
Kohshour, M. O., Adorjan, K., Budde, M., Heilbronner, M., Kalman, J. L., Navarro‐Flores, A., Reich‐Erkelenz, D., Schulte, E. C., Senner, F., Vogl, T., et al. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116492 · Cited by 4
“…those pertaining to inflammatory cytokines, to the etiology, development, and severity of psychiatric disorders (Bull et al., 2009; Felger and Lotrich, 2013; Kalmady et al., 2014; Khandaker et al., 2018; Mikhalitskaya et al., 2023; Momtazmanesh et al., 2019; Rodrigues-A-morim et al., 2018).”
Inflammation, Sickness Behaviour and Depression
Khandaker, G. M., Colasanti, A., & Harrison, N. A. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108539623.008 · Cited by 5
Self-citationWeaving Causal Explanations of Schizophrenia in Urban Areas
Jongsma, H. E., & Jones, P. B. (2018) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2018.1795 · Cited by 4
Self-citationFrycz, B. A., Dutsch-Wicherek, M., Płaza, O., Szulc, A., Bijata, M., Włodarczyk, J., & Dzwonek, J. (2026) · Pharmacological Reports · doi:10.1007/s43440-026-00827-9 · Cited by 2
Anti-inflammatory Drugs in the Treatment of Depression
Cavanagh, J. (2023) · Current topics in behavioral neurosciences · doi:10.1007/7854_2023_459 · Cited by 6
Tsermpini, E. E., Goričar, K., Plesničar, B. K., Ilješ, A. P., & Dolžan, V. (2023) · Antioxidants · doi:10.3390/antiox13010020 · Cited by 4
“Within our study, we also found an association between IL6R rs2228145 and compulsions in alcohol-addicted patients and aggressive symptomatology in healthy individuals. rs2228145 has been associated with decreased IL-6-induced C-reactive protein (CRP) levels [32] and depression severity [33].”
Hallab, A., & The Health and Aging Brain Study (HABS-HD) Study Team (2025) · medRxiv · doi:10.1101/2025.04.14.25325836 · Cited by 3
Lee, S. W., Lee, Y. L., Kang, C., Cho, H., Park, J. H., Dong, J. J., Wolde, H. M., Shin, W., Jung, H., & Bae, Y. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1686890 · Cited by 2
Tang, Y., Huang, Y., Pan, J., Li, C., Yang, J., Tan, X., 胡康安, Wen, L., Xie, P., Liu, Y., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03593-5 · Cited by 4
“Similarly, variants in IL6R have been negatively associated with severe depression and psychosis [8].”
Nakagawa, R., Nakashima, H., Sato, M., Nagamine, M., Kinoshita, M., Asai, F., Yoshino, A., Toda, H., & Koga, M. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149787 · Cited by 2
Borovčanin, M., Milovanović, M., Vesić, K., Muric, N. N., Milovanović, J., Arsenijević, A., & Arsenijević, N. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85415-3.00011-8 · Cited by 2
Francesconi, M., Minichino, A., Khandaker, G. M., Midouhas, E., Lewis, G., & Flouri, E. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.11.009 · Cited by 1
Self-citationZhang, J., Zhang, Y., Chen, Y., & Zhu, J. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.119519 · Cited by 1
Sayed, M. M., Gaafary, M. M. E., Elsheikh, M. M. E., Hamed, S. S., Mohamed, R. M. A., & Mohamed, M. Y. (2025) · Middle East Current Psychiatry · doi:10.1186/s43045-025-00549-3 · Cited by 1
“Retrospective studies indicate that early-life inflammation may predict later depressive symptoms [15, 36].”
Metadata
- Authors
- Khandaker, G. M., Zammit, S., Burgess, S., Lewis, G., & Jones, P. B.
- Affiliations
- University of Cambridge (GB)
- University of Bristol (GB)
- University College London (GB)
- Corresponding author
- Khandaker, Golam M.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 69
- Pages
- 264-272
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC5871397
- OpenAlex
- W2774979768
- Cited by
- 118
- References
- 67
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 17 · 2020: 20 · 2019: 18 · 2018: 10
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust (204623/Z/16/Z, 102215/2/13/2), 088869/Z/09/Z, 095844/Z/11/Z, 088869, 102215, /Z/11/Z, 100114, 102215/2/13/, 201486 /Z/16/Z, 80354, 201486, 100114/Z/12/Z, 095844)
- NIHR Bristol Biomedical Research Centre
- National Institute for Health and Care Research (NF-SI-0617-10113, NF-SI-0512-10165, RP-PG-0606-1335)
- British Heart Foundation (RG/13/13/30194)
- Academy of Medical Sciences (AMS-SGCL13-Khandaker, 80354)
- University of Bristol (102215/2/13/2, 201486/Z/16/Z)
- Medical Research Council (102215, ref: 102215/2/13/2, MR/L003120/1, 201486/Z/16/Z, 102215/2/13/2, MR/L010305/1, MC_PC_15018)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- IL-6 receptor, rs2228145, depression, psychosis, interleukin-6, C-reactive protein, inflammation, genetic susceptibility, ALSPAC birth cohort, childhood risk factors, postpartum depression
- MeSH terms
- Adolescent, C-Reactive Protein, Child, Depressive Disorder, Female, Genotype, Humans, Male, Psychotic Disorders, Cohort Studies, Interleukin-6, Receptors, Interleukin-6, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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
