Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder
•This meta-analysis confirms a robust link between IL-6, CRP and major depression.•The role of TNF-α and IL-1β in major depression remains uncertain.•Further mechanistic and immunotherapeutic studies on IL-6 and CRP are needed. Cumulative meta-analyses are used to evaluate the extent to which furthe...
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| Published in | Brain, behavior, and immunity Vol. 49; pp. 206 - 215 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Inc
01.10.2015
Academic Press |
| Subjects | |
| Online Access | Get full text |
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| Abstract | •This meta-analysis confirms a robust link between IL-6, CRP and major depression.•The role of TNF-α and IL-1β in major depression remains uncertain.•Further mechanistic and immunotherapeutic studies on IL-6 and CRP are needed.
Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d=0.54, p<0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d=0.47, p<0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d=0.40, p=0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d=−0.05, p=0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression. |
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| AbstractList | Highlights • This meta-analysis confirms a robust link between IL-6, CRP and major depression. • The role of TNF-α and IL-1β in major depression remains uncertain. • Further mechanistic and immunotherapeutic studies on IL-6 and CRP are needed. •This meta-analysis confirms a robust link between IL-6, CRP and major depression.•The role of TNF-α and IL-1β in major depression remains uncertain.•Further mechanistic and immunotherapeutic studies on IL-6 and CRP are needed. Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d=0.54, p<0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d=0.47, p<0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d=0.40, p=0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d=−0.05, p=0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression. • This meta-analysis confirms a robust link between IL-6, CRP and major depression. • The role of TNF-α and IL-1β in major depression remains uncertain. • Further mechanistic and immunotherapeutic studies on IL-6 and CRP are needed. Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding ( d = 0.54, p < 0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies ( d = 0.47, p < 0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression ( d = 0.40, p = 0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression ( d = −0.05, p = 0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression. Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d=0.54, p<0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d=0.47, p<0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d=0.40, p=0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d=-0.05, p=0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression. Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d =0.54, p <0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d =0.47, p <0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor- alpha levels and major depression (d =0.40, p =0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1 beta levels and major depression (d =-0.05, p =0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor- alpha , interleukin-1 beta and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression. |
| Author | Haapakoski, Rita Alenius, Harri Kivimäki, Mika Mathieu, Julia Ebmeier, Klaus P. |
| AuthorAffiliation | c Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK b Finnish Institute of Occupational Health, Systems Toxicology Unit, Centre of Expertise for Health and Work Ability, Helsinki, Finland d Université Pierre et Marie Curie, Paris, France a Department of Epidemiology and Public Health, University College London, London, UK e Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland |
| AuthorAffiliation_xml | – name: b Finnish Institute of Occupational Health, Systems Toxicology Unit, Centre of Expertise for Health and Work Ability, Helsinki, Finland – name: d Université Pierre et Marie Curie, Paris, France – name: e Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland – name: a Department of Epidemiology and Public Health, University College London, London, UK – name: c Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK |
| Author_xml | – sequence: 1 givenname: Rita orcidid: 0000-0001-5263-0870 surname: Haapakoski fullname: Haapakoski, Rita email: r.haapakoski@ucl.ac.uk organization: Department of Epidemiology and Public Health, University College London, London, UK – sequence: 2 givenname: Julia surname: Mathieu fullname: Mathieu, Julia organization: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK – sequence: 3 givenname: Klaus P. surname: Ebmeier fullname: Ebmeier, Klaus P. organization: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK – sequence: 4 givenname: Harri surname: Alenius fullname: Alenius, Harri organization: Finnish Institute of Occupational Health, Systems Toxicology Unit, Centre of Expertise for Health and Work Ability, Helsinki, Finland – sequence: 5 givenname: Mika surname: Kivimäki fullname: Kivimäki, Mika organization: Department of Epidemiology and Public Health, University College London, London, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26065825$$D View this record in MEDLINE/PubMed |
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| Snippet | •This meta-analysis confirms a robust link between IL-6, CRP and major depression.•The role of TNF-α and IL-1β in major depression remains uncertain.•Further... Highlights • This meta-analysis confirms a robust link between IL-6, CRP and major depression. • The role of TNF-α and IL-1β in major depression remains... Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess... • This meta-analysis confirms a robust link between IL-6, CRP and major depression. • The role of TNF-α and IL-1β in major depression remains uncertain. •... |
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| SubjectTerms | Adult Allergy and Immunology C-reactive protein C-Reactive Protein - immunology C-Reactive Protein - metabolism Cumulative meta-analysis Depressive Disorder, Major - blood Depressive Disorder, Major - complications Depressive Disorder, Major - immunology Female Humans Inflammation Inflammation - blood Inflammation - complications Inflammation - immunology Inflammation Mediators - blood Inflammation Mediators - immunology Interleukin-1beta - blood Interleukin-1beta - immunology Interleukin-1β Interleukin-6 Interleukin-6 - blood Interleukin-6 - immunology Major depression Male Psychiatry Tumor Necrosis Factor-alpha - blood Tumor Necrosis Factor-alpha - immunology Tumour necrosis factor-α |
| Title | Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder |
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