Elevated inflammation levels in depressed adults with a history of childhood maltreatment
Open accessAbstract
CONTEXT: The association between depression and inflammation is inconsistent across research samples. OBJECTIVE: To test whether a history of childhood maltreatment could identify a subgroup of depressed individuals with elevated inflammation levels, thus helping to explain previous inconsistencies. DESIGN: Prospective longitudinal cohort study. SETTING: New Zealand. PARTICIPANTS: A representative birth cohort of 1000 individuals was followed up to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Study members were assessed for history of childhood maltreatment and current depression. MAIN OUTCOME MEASURES: Inflammation was assessed using a clinically relevant categorical measure of high-sensitivity C-reactive protein (>3 mg/L) and a dimensional inflammation factor indexing the shared variance of continuous measures of high-sensitivity C-reactive protein, fibrinogen, and white blood cells. RESULTS: Although depression was associated with high levels of high-sensitivity C-reactive protein (relative risk,1.45; 95% confidence interval,1.06-1.99), this association was significantly attenuated and no longer significant when the effect of childhood maltreatment was taken into account. Individuals with current depression and a history of childhood maltreatment were more likely to have high levels of high-sensitivity C-reactive protein compared with control subjects (n = 27; relative risk, 2.07; 95% confidence interval, 1.23-3.47). In contrast, individuals with current depression only had a nonsignificant elevation in risk (n = 109; relative risk, 1.40; 95% confidence interval, 0.97-2.01). Results were generalizable to the inflammation factor. The elevated inflammation levels in individuals who were both depressed and maltreated were not explained by correlated risk factors such as depression recurrence, low socioeconomic status in childhood or adulthood, poor health, or smoking. CONCLUSIONS: A history of childhood maltreatment contributes to the co-occurrence of depression and inflammation. Information about experiences of childhood maltreatment may help to identify depressed individuals with elevated inflammation levels and, thus, at greater risk of cardiovascular disease.
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- Findingown data
Maltreated individuals had elevated high hsCRP (RR=1.71; 95% CI 1.22-2.41).
“maltreated individuals had elevated levels of inflammation markers (high hsCRP: RR=1.71; 95%CI=1.22;2.41”
Quote in the paperSubstantial claim - Findingown data
Recurrent depression was associated with significantly elevated mean inflammation factor levels (b=0.09; 95% CI 0.00-0.17).
“and significantly elevated mean levels of the inflammation factor (b=0.09; 95%CI=0.00,0.17)”
Quote in the paperNot a substantial claim - Findingown data
Recurrent depression was associated with a non-significant elevation in risk for high hsCRP (RR=1.11; 95% CI 0.94-1.31).
“individuals with recurrent depression showed non-significant elevation in risk for high hsCRP (RR=1.11; 95%CI=0.94,1.31)”
Quote in the paperNot a substantial claim - Findingown data
After controlling for adult SES, the association between depression+maltreatment and inflammation markers remained significant.
“However, after controlling for adult SES, the association between depression+maltreatment and inflammation markers remained significant (Table 3, Model 5).”
Quote in the paperSubstantial claim - Findingown data
The cardiovascular risk cluster was associated with elevated high hsCRP (RR=2.39; 95% CI 1.84-3.10).
“The cardiovascular risk cluster was associated with elevated inflammation in adulthood (high hsCRP: RR=2.39; 95%CI=1.84,3.10”
Quote in the paperNot a substantial claim
- Findingown data
Depression was associated with high hsCRP (RR=1.45; 95% CI 1.06-1.99).
“Although depression was associated with high hsCRP (RR=1.45; 95%CI=1.06;1.99)”
- Also stated in: § Is depression associated with inflammation? · plain
“Depression was associated with inflammation markers (high hsCRP: RR=1.45; 95%CI=1.06;1.99”
Quote in the paperSubstantial claim - Also stated in: § Is depression associated with inflammation? · plain
- Findingown data
Depressed+maltreated participants were more likely to smoke.
“Consistent with the “health-behavior hypothesis,” depressed+maltreated participants were more likely to smoke (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
After controlling for childhood SES, the association between depression+maltreatment and inflammation markers remained significant.
“However, after controlling for the effect of childhood SES, the association between depression+maltreatment and inflammation markers remained significant (Table 3, Model 4).”
Quote in the paperSubstantial claim - Findingown data
Depression was associated with the inflammation factor (b=0.18; 95% CI 0.00-0.36).
“inflammation factor: b=0.18; 95%CI=0.00;0.36”
Quote in the paperSubstantial claim - Findingown data
The prevalence of the cardiovascular risk cluster did not differ across study groups.
“we found that the prevalence of the cardiovascular risk cluster did not differ across study groups (Table 1).”
Quote in the paperSubstantial claim - Findingown data
Smoking was not associated with the risk for high hsCRP (RR=0.98; 95% CI 0.84-1.13).
“but was not associated with the risk for high hsCRP levels (RR=0.98; 95%CI=0.84,1.13)”
Quote in the paperNot a substantial claim - Findingown data
Low childhood SES was associated with elevated inflammation factor levels (b=0.26; 95% CI 0.15-0.37).
“inflammation factor: b=0.26; 95%CI=0.15,0.37)”
Quote in the paperNot a substantial claim - Findingown data
Low childhood SES was associated with elevated high hsCRP in adulthood (RR=1.36; 95% CI 1.09-1.68).
“low childhood SES was associated with elevated inflammation in adulthood (high hsCRP: RR=1.36; 95%CI=1.09,1.68”
Quote in the paperNot a substantial claim - Findingown data
There was no systematic difference in depressive symptom presentation between depressed+maltreated and depressed-only individuals.
“We found no systematic difference in symptom presentation (Table 2)”
Quote in the paperNot a substantial claim - Findingown data
Within depressed individuals, those with depression+maltreatment had higher mean inflammation factor levels than depressed-only individuals (0.48 vs 0.07, F=2.88; p=0.09).
“had higher mean levels of the inflammation factor (0.48 versus 0.07, F=2.88; p=0.09) than individuals with depression-only”
Quote in the paperSubstantial claim - Findingown data
Depressed+maltreated participants were more likely to have experienced multiple depressive episodes.
“Consistent with the “depression-history hypothesis,” depressed+maltreated participants were more likely to have experienced multiple depressive episodes (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
Maltreated individuals had elevated inflammation factor scores (b=0.36; 95% CI 0.14-0.59).
“inflammation factor: b=0.36; 95%CI=0.14;0.59”
Quote in the paperSubstantial claim - Findingown data
Low adult SES was associated with elevated inflammation factor levels (b=0.13; 95% CI 0.05-0.21).
“inflammation factor: b=0.13; 95%CI=0.05,0.21)”
Quote in the paperNot a substantial claim - Findingown data
Smoking was associated with elevated mean inflammation factor levels (b=0.13; 95% CI 0.06-0.20).
“smoking was associated with elevated mean levels of the inflammation factor (b=0.13; 95%CI=0.06,0.20)”
Quote in the paperNot a substantial claim - Findingown data
After controlling for cardiovascular risk clustering, the association between depression+maltreatment and inflammation markers remained significant.
“After controlling for cardiovascular risk clustering, the association between depression+maltreatment and inflammation markers remained significant (Table 3, Model 6).”
Quote in the paperSubstantial claim - Findingown data
A Sobel-Goodman test confirmed statistically significant attenuation of the depression-inflammation association after adjustment for maltreatment history (19.2% reduction for hsCRP, z=2.277, p=0.023; 22.2% reduction for the inflammation factor, z=2.451, p=0.014).
“A Sobel-Goodman test confirmed a statistically significant attenuation of the association between depression and inflammation markers after adjustment for maltreatment history (reduction of 19.2% for hsCRP, z=2.277, p=0.023; reduction of 22.2% for the inflammation factor, z=2.451, p=0.014).”
Quote in the paperSubstantial claim - Findingown data
Depressed+maltreated participants were more likely to have low adult SES.
“Consistent with the “adulthood-risk hypothesis,” depressed+maltreated participants were more likely to have low adult SES (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
Low adult SES was associated with elevated high hsCRP (RR=1.17; 95% CI 1.00-1.38).
“low adult SES was associated with elevated inflammation in adulthood (high hsCRP: RR=1.17; 95%CI=1.00,1.38”
Quote in the paperNot a substantial claim - Findingown data
After controlling for smoking, the association between depression+maltreatment and inflammation markers remained significant.
“After controlling for smoking, the association between depression+maltreatment and inflammation markers remained significant (Table 3, Model 7).”
Quote in the paperSubstantial claim - Findingown data
Individuals with current depression and a history of childhood maltreatment were more likely to show high hsCRP than controls (N=27; RR=2.07; 95% CI 1.23-3.47).
“Individuals with current depression and childhood maltreatment history were more likely to show high hsCRP levels than controls (N=27; RR=2.07; 95%CI=1.23;3.47).”
Quote in the paperSubstantial claim - Findingown data
Depressed+maltreated participants were more likely to have grown up in low-SES families.
“Consistent with the “childhood-risk hypothesis,” depressed+maltreated participants were more likely to have grown up in low-SES families (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
Within depressed individuals, those with depression+maltreatment were 1.48 times more likely to show high hsCRP than depressed-only individuals (95% CI 0.82-2.68).
“Individuals with depression+maltreatment were 1.48 times (95%CI=0.82;2.68) more likely to show high hsCRP levels”
Quote in the paperSubstantial claim - Findingown data
The cardiovascular risk cluster was associated with elevated inflammation factor levels (b=0.87; 95% CI 0.70-1.04).
“inflammation factor: b=0.87; 95%CI=0.70,1.04)”
Quote in the paperNot a substantial claim - Findingown data
After controlling for recurrent depression history, the association between age-32 depression+maltreatment and inflammation markers remained significant.
“However, after controlling for recurrent depression history, the association between age-32 depression+maltreatment and inflammation markers remained significant (Table 3, Model 3).”
Quote in the paperSubstantial claim - Findingown data
Individuals with current depression only showed a non-significant elevation in risk for high hsCRP (N=109; RR=1.40; 95% CI 0.97-2.01).
“In contrast, individuals with current depression only showed a non-significant elevation in risk (N=109; RR=1.40; 95%CI=0.97;2.01).”
Quote in the paperSubstantial claim - Findingown data
Childhood maltreatment was more common among depressed than non-depressed individuals (RR=2.40; 95% CI 1.58-3.63).
“childhood maltreatment was more common in depressed than in non-depressed individuals (RR=2.40; 95%CI=1.58;3.63)”
Quote in the paperSubstantial claim - Findingown data
The continuous measures of log-transformed hsCRP, fibrinogen and WBC at age 32 were positively correlated (range r=.20 to .63).
“the continuous measures of (log-transformed) hsCRP, fibrinogen and WBC at age 32 were positively correlated (range r= .20 to .63).”
Quote in the paperSubstantial claim - Interpretationcitation
Elevated inflammation levels and cardiovascular disease risk observed in individuals with a history of depression but no current depression may be due to the long-term effect of childhood maltreatment.
“Results also suggest that elevated inflammation levels and cardiovascular disease risk observed in individuals with a history of depression but no current depression may be due to the long-term effect of childhood maltreatment7,17.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [7] Danese A Pariante CM Caspi A Taylor A Poulton R Childhood maltreatment predicts adult inflammation in a life-course study Proc Natl Acad Sci USA 2007 104 1319 24 17229839 PMC1783123
Not checked in the free run.
- cites [17] Dong M Giles WH Felitti VJ Dube SR Williams JE Chapman DP Anda RF Insights into causal pathways for ischemic heart disease: adverse childhood experiences study Circulation 2004 110 1761 6 15381652
Not checked in the free run.
- Premisecitation
Childhood maltreatment predicts adult inflammation.
“Evidence that childhood maltreatment - a major risk factor for depression - predicts adult inflammation7”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] Danese A Pariante CM Caspi A Taylor A Poulton R Childhood maltreatment predicts adult inflammation in a life-course study Proc Natl Acad Sci USA 2007 104 1319 24 17229839 PMC1783123
Not checked in the free run.
- Rests on an assumption: Childhood maltreatment is a major risk factor for depression.
- Interpretationreasoning
Previous inconsistencies across studies in the depression-inflammation association could be due to variation in the prevalence of childhood maltreatment in different samples.
“This suggests that previous inconsistencies across studies could be due to variation in the prevalence of childhood maltreatment in different samples.”
Quote in the paperSubstantial claim - Interpretationown data
A history of childhood maltreatment contributes to the co-occurrence of depression and inflammation in adulthood.
“A history of childhood maltreatment contributes to the co-occurrence of depression and inflammation.”
- Also stated in: § CONCLUSIONS · hedged
“The results suggest that a history of maltreatment has a significant role in explaining the co-occurrence of depression and inflammation in adulthood.”
Quote in the paperSubstantial claim - Also stated in: § CONCLUSIONS · hedged
- Premisereasoning
Depressed individuals may be at higher risk for inflammation.
“and may therefore be at higher risk for inflammation11.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Miller GE Stetler CA Carney RM Freedland KE Banks WA Clinical depression and inflammatory risk markers for coronary heart disease Am J Cardiol 2002 90 1279 83 12480034
Not checked in the free run.
- Interpretationown data
Information about childhood maltreatment experiences may help identify depressed individuals with elevated inflammation levels and thus cardiovascular disease risk.
“Information about experiences of childhood maltreatment may help to identify depressed individuals with elevated inflammation levels and thus cardiovascular disease risk.”
Quote in the paperSubstantial claim - Interpretationown data
Other commonly assessed factors with potential influence on inflammation processes do not account for the effect of childhood maltreatment on adult inflammation in depressed individuals.
“we showed that other commonly assessed factors with potential influence on inflammation processes do not account for the effect of childhood maltreatment on adult inflammation in depressed individuals (see Table 3).”
Quote in the paperSubstantial claim - Premisecitation
Not all individuals with depression show elevated inflammation levels.
“Yet, not all individuals with depression show elevated inflammation levels5.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Raison CL Capuron L Miller AH Cytokines sing the blues: inflammation and the pathogenesis of depression Trends Immunol 2006 27 24 31 16316783 PMC3392963
Not checked in the free run.
- Interpretationown data
In this cohort, the information conveyed by maltreatment history was not captured by information about symptom presentation during the depressive episode.
“in our cohort the information conveyed by maltreatment history was not captured by information about symptom presentation during the depressive episode (see Table 2).”
Quote in the paperSubstantial claim - Premisecitation
Depressed individuals often show impaired glucocorticoid signaling.
“Depressed individuals often show impaired glucocorticoid signaling10”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] Pariante CM Miller AH Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment Biol Psychiatry 2001 49 391 404 11274650
Not checked in the free run.
- Premisecitation
Therapeutic reduction in inflammation levels decreases cardiovascular disease risk.
“Moreover, therapeutic reduction in inflammation levels decreases cardiovascular disease risk13.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Ridker PM Cannon CP Morrow D Rifai N Rose LM McCabe CH Pfeffer MA Braunwald E C-reactive protein levels and outcomes after statin therapy N Engl J Med 2005 352 20 8 15635109
Not checked in the free run.
- Interpretationreasoning
A subgroup of depressed individuals with stressful developmental experiences may be at highest risk for future disease.
“It is possible that a subgroup of depressed individuals with stressful developmental experiences is at highest risk for future disease.”
Quote in the paperSubstantial claim - Premisecitation
All three inflammatory measures index long-term risk for cardiovascular disease.
“Given that all three inflammatory measures index long-term risk for cardiovascular disease23”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Danesh J Collins R Appleby P Peto R Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies JAMA 1998 279 1477 82 9600484
Not checked in the free run.
- Study design and conductown data
The test comparing depressed+maltreated to depressed-only individuals was compromised by low power.
“This test was compromised by low power, as it involved comparing 27 depressed+maltreated individuals to 109 depressed-only individuals.”
Quote in the paperNot a substantial claim - Premisecitation
Only the experience of two or more indicators of childhood maltreatment significantly predicted inflammation in adulthood.
“We previously reported that only the experience of two or more indicators of childhood maltreatment significantly predicted inflammation in adulthood7.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] Danese A Pariante CM Caspi A Taylor A Poulton R Childhood maltreatment predicts adult inflammation in a life-course study Proc Natl Acad Sci USA 2007 104 1319 24 17229839 PMC1783123
Not checked in the free run.
- Study design and conductown data
A principal-component analysis identified a single inflammation factor accounting for 59% of the variance in the continuous measures of the three markers.
“A principal-component analysis identified a single inflammation factor accounting for 59% of the variance in the continuous measures of these three markers of inflammation7.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] Danese A Pariante CM Caspi A Taylor A Poulton R Childhood maltreatment predicts adult inflammation in a life-course study Proc Natl Acad Sci USA 2007 104 1319 24 17229839 PMC1783123
Not checked in the free run.
- Study design and conductown data
Lacking measures of inflammation markers before the onset of depression, the study is unable to test the direction of the effect.
“lacking measures of inflammation markers before the onset of depression, we are unable to test the direction of the effect.”
Quote in the paperSubstantial claim - Premisecitation
Inflammation persists in individuals with a history of depression even when depressive symptoms are absent.
“inflammation persists in individuals with a history of depression even when their depressive symptoms are absent15.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Kling MA Alesci S Csako G Costello R Luckenbaugh DA Bonne O Duncko R Drevets WC Manji HK Charney DS Gold PW Neumeister A Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A Biol Psychiatry 2007 62 309 13 17178112 PMC2546515
Not checked in the free run.
- Premisecitation
Depression, inflammation, and cardiovascular disease may share common origins in early-life stress such as childhood maltreatment.
“Initial evidence suggests that depression, inflammation, and cardiovascular disease may share common origins in early-life stress, such as childhood maltreatment7,16,17.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [7] Danese A Pariante CM Caspi A Taylor A Poulton R Childhood maltreatment predicts adult inflammation in a life-course study Proc Natl Acad Sci USA 2007 104 1319 24 17229839 PMC1783123
Not checked in the free run.
- cites [16] Widom CS DuMont K Czaja SJ A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up Arch Gen Psychiatry 2007 64 49 56 17199054
Not checked in the free run.
- cites [17] Dong M Giles WH Felitti VJ Dube SR Williams JE Chapman DP Anda RF Insights into causal pathways for ischemic heart disease: adverse childhood experiences study Circulation 2004 110 1761 6 15381652
Not checked in the free run.
- Premisecitation
Studies testing the association between depression and inflammation have reported inconsistent results.
“studies testing the association between depression and inflammation have reported inconsistent results5.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Raison CL Capuron L Miller AH Cytokines sing the blues: inflammation and the pathogenesis of depression Trends Immunol 2006 27 24 31 16316783 PMC3392963
Not checked in the free run.
- Premisecitation
Poor prognosis of heart disease persists in individuals with a history of depression even when depressive symptoms have been significantly reduced by treatment.
“poor prognosis of heart disease, which can be influenced by inflammation, persists in individuals with a history of depression even when depressive symptoms have been significantly reduced by treatment4.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] Berkman LF Blumenthal J Burg M Carney RM Catellier D Cowan MJ Czajkowski SM DeBusk R Hosking J Jaffe A Kaufmann PG Mitchell P Norman J Powell LH Raczynski JM Schneiderman N Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial JAMA 2003 289 3106 16 12813116
Not checked in the free run.
- May combine two claims. 7
- Classified as probably not a substantial claim. 20
May combine two claims.
Findingown dataDepressed+maltreated and, to a lesser extent, maltreated-only individuals were more likely to show high hsCRP and higher mean inflammation factor levels than controls, whereas depressed-only individuals showed a non-significant elevation.
“Depressed+maltreated and, to a lesser extent, maltreated-only individuals were more likely to show high hsCRP levels and higher mean levels of the inflammation factor than controls.”
- Also stated in: § Which depressed individuals show increased inflammation? · plain
“In contrast, depressed-only individuals showed a non-significant elevation in inflammatory markers”
Quote in the paperSubstantial claim- Also stated in: § Which depressed individuals show increased inflammation? · plain
May combine two claims.
Findingown dataAfter adjustment for childhood maltreatment history, the association between depression and the inflammation factor was attenuated and no longer statistically significant (b=0.14; 95% CI −0.04-0.32).
“inflammation factor: b=0.14; 95%CI= -0.04,0.32”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAfter adjustment for childhood maltreatment history, the association between depression and high hsCRP was attenuated and no longer statistically significant (RR=1.35; 95% CI 0.98-1.86).
“Once the effect of maltreatment history was taken into account, the association between depression and inflammation markers was attenuated and no longer significant (high hsCRP: RR=1.35; 95%CI=0.98,1.86”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
FindingcitationThe past-year depression prevalence in the Dunedin cohort was 16%, comparable to the past-year prevalence of 12% for 15-34 year olds in the National Comorbidity Survey.
“At age 32, the past-year depression prevalence in the Dunedin cohort was 16% (62% female), which is comparable to the past-year prevalence of 12% for 15-34 year olds in the National Comorbidity Survey22.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Kessler RC McGonagle KA Swartz M Blazer DG Nelson CB Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence J Affect Disord 1993 29 85 96 8300981
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEven mild rises in inflammation levels appear to predict increased risk of cardiovascular disease in apparently healthy individuals.
“Even mild rises in inflammation levels appear to predict increased risk of cardiovascular disease in apparently healthy individuals6.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [6] Ridker PM Cushman M Stampfer MJ Tracy RP Hennekens CH Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men N Engl J Med 1997 336 973 9 9077376
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
Interpretationown dataRoutine assessment of maltreatment history could provide clinicians with information to identify depressed individuals with elevated risk of inflammation and potentially poor health.
“we suggest that routine assessment of maltreatment history could provide clinicians with necessary information to identify depressed individuals with elevated risk of inflammation and potentially poor health.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationInflammation has been associated with both depression and cardiovascular disease.
“inflammation has been associated with both conditions5,6”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [5] Raison CL Capuron L Miller AH Cytokines sing the blues: inflammation and the pathogenesis of depression Trends Immunol 2006 27 24 31 16316783 PMC3392963
Not checked in the free run.
- cites [6] Ridker PM Cushman M Stampfer MJ Tracy RP Hennekens CH Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men N Engl J Med 1997 336 973 9 9077376
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMajor depression is a multi-systemic disorder affecting both brain and bodily functions.
“Major depression is a multi-systemic disorder affecting both brain and bodily functions1.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Insel TR Charney DS Research on major depression: strategies and priorities JAMA 2003 289 3167 8 12813123
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationInflammation may be related to depression through two-way neuro-immunoendocrine interactions.
“Inflammation may be related to depression through two-way neuro-immunoendocrine interactions.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] Sternberg EM Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens Nat Rev Immunol 2006 6 318 28 16557263 PMC1783839
Not checked in the free run.
- cites [9] Pace TW Hu F Miller AH Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression Brain Behav Immun 2007 21 9 19 17070667 PMC1820632
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationDepression and cardiovascular disease often co-occur.
“depression and cardiovascular disease often co-occur3,4”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [3] Frasure-Smith N Lesperance F Talajic M Depression following myocardial infarction. Impact on 6-month survival JAMA 1993 270 1819 25 8411525
Not checked in the free run.
- cites [4] Berkman LF Blumenthal J Burg M Carney RM Catellier D Cowan MJ Czajkowski SM DeBusk R Hosking J Jaffe A Kaufmann PG Mitchell P Norman J Powell LH Raczynski JM Schneiderman N Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial JAMA 2003 289 3106 16 12813116
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInflammation is related to cardiovascular disease through its involvement in the pathophysiology of atherosclerosis.
“Inflammation is also related to cardiovascular disease, through its involvement in the pathophysiology of atherosclerosis12.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Pepys MB Hirschfield GM C-reactive protein: a critical update J Clin Invest 2003 111 1805 12 12813013 PMC161431
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInflammation may contribute to the link between psychological and somatic symptoms in depressed individuals.
“Increasing evidence suggests that inflammation may contribute to the link between psychological and somatic symptoms in depressed individuals2.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Evans DL Charney DS Lewis L Golden RN Gorman JM Krishnan KR Nemeroff CB Bremner JD Carney RM Coyne JC Delong MR Frasure-Smith N Glassman AH Gold PW Grant I Gwyther L Ironson G Johnson RL Kanner AM Katon WJ Kaufmann PG Keefe FJ Ketter T Laughren TP Leserman J Lyketsos CG McDonald WM McEwen BS Miller AH Musselman D O’Connor C Petitto JM Pollock BG Robinson RG Roose SP Rowland J Sheline Y Sheps DS Simon G Spiegel D Stunkard A Sunderland T Tibbits P Jr. Valvo WJ Mood disorders in the medically ill: scientific review and recommendations Biol Psychiatry 2005 58 175 89 16084838
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductcitationClinical interviews for the diagnosis of depression at age 32 used the Diagnostic Interview Schedule and followed DSM-IV.
“Clinical interviews for the diagnosis of depression at age 32 used the Diagnostic Interview Schedule (DIS)20, and followed DSM-IV21.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [20] Robins LN Cottler L Bucholz KK Compton W The Diagnostic Interview Schedule for DSM-IV 1995 Washington University St. Louis, MO
Not checked in the free run.
- cites [21] American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders 1994 American Psychiatric Association Washington, DC 4th edn.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataPregnant women were excluded from the reported analyses.
“Pregnant women (N=26) were excluded from the reported analyses.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationDepressed adults with increased early-life stress have greater inflammatory response to an acute psychosocial stress challenge than non-depressed controls.
“Experimental research also shows that depressed adults with increased early-life stress have greater inflammatory response to an acute psychosocial stress challenge than non-depressed controls”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Pace TW Mletzko TC Alagbe O Musselman DL Nemeroff CB Miller AH Heim CM Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress Am J Psychiatry 2006 163 1630 3 16946190
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenThe study is a prospective longitudinal cohort study.
“Prospective longitudinal cohort study.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationhsCRP>3mg/L is the CDC/AHA definition of high cardiovascular risk.
“We adopted the CDC/AHA definition of high cardiovascular risk (hsCRP>3mg/L) to identify our risk group14.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Pearson TA Mensah GA Alexander RW Anderson JL Cannon RO III Criqui M Fadl YY Fortmann SP Hong Y Myers GL Rifai N Smith SC Jr. Taubert K Tracy RP Vinicor F Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association Circulation 2003 107 499 511 12551878
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenParticipants represent the full range of socioeconomic status in the general population of New Zealand's South Island and are primarily white.
“Participants represent the full range of socioeconomic status in the general population of New Zealand’s South Island and are primarily white.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenSex and medication use were controlled for in all adjusted analyses.
“Sex and medication use were controlled for in all adjusted analyses.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenPhysical examinations and venepuncture were always conducted between 4:15 and 4:45 pm.
“Physical examinations and venepuncture (always between 4:15-4:45 pm) were conducted at the age-32 assessment”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInflammation has been hypothesized to partly explain the comorbidity between depression and cardiovascular disease.
“Inflammation has therefore been hypothesized to partly explain the observed comorbidity between depression and cardiovascular disease2”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Evans DL Charney DS Lewis L Golden RN Gorman JM Krishnan KR Nemeroff CB Bremner JD Carney RM Coyne JC Delong MR Frasure-Smith N Glassman AH Gold PW Grant I Gwyther L Ironson G Johnson RL Kanner AM Katon WJ Kaufmann PG Keefe FJ Ketter T Laughren TP Leserman J Lyketsos CG McDonald WM McEwen BS Miller AH Musselman D O’Connor C Petitto JM Pollock BG Robinson RG Roose SP Rowland J Sheline Y Sheps DS Simon G Spiegel D Stunkard A Sunderland T Tibbits P Jr. Valvo WJ Mood disorders in the medically ill: scientific review and recommendations Biol Psychiatry 2005 58 175 89 16084838
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductown dataChildhood maltreatment during the first decade of life was ascertained using parental reports, prospective behavioral observations, and retrospective reports by Study members.
“evidence of childhood maltreatment during the first decade of life (ages 3-11) was ascertained using parental reports, prospective behavioral observations, and retrospective reports by Study members once they reached adulthood.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
Study design and conductnone givenFindings from this New Zealand cohort require replication in other studies and in different ethnic groups.
“findings from this New Zealand cohort require replication in other studies and in different ethnic groups.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationhsCRP has been endorsed as an adjunct to traditional risk-factor screening for cardiovascular disease.
“a marker of inflammation – the high-sensitivity C-reactive protein (hsCRP) - has been recently endorsed as an adjunct to traditional risk-factor screening for cardiovascular disease14.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Pearson TA Mensah GA Alexander RW Anderson JL Cannon RO III Criqui M Fadl YY Fortmann SP Hong Y Myers GL Rifai N Smith SC Jr. Taubert K Tracy RP Vinicor F Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association Circulation 2003 107 499 511 12551878
Not checked in the free run.
The paper relies on this without support.
Childhood maltreatment is a major risk factor for depression.
“Evidence that childhood maltreatment - a major risk factor for depression - predicts adult inflammation7”
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?
Most findings, but not all, suggest a robust correlation between ELS/CT and adult CRP levels.
“Most findings, but not all, suggest a robust correlation between ELS/CT and adult CRP levels (165, 166, 170, 199–202).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [166]
The Results section (page not provided) reports higher hsCRP in adults with both childhood maltreatment and current depression than in controls, with a lesser elevation in the maltreated-only group. This supports an association, but this single study does not establish that most findings show a robust correlation across adults generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPositive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (a pro-inflammatory phenotype) in adulthood.
“There is growing evidence suggesting that positive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (i.e., a pro-inflammatory phenotype) in adulthood (101, 164–172).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [166]
The Results report elevated inflammatory markers at age 32 among people with childhood maltreatment, and the Conclusions state that maltreatment history conferred elevated inflammation risk even without current depression. The Results also show that the depression-plus-maltreatment association remained significant after adjustment for several other risk factors. The paper measured inflammation at age 32; it does not establish that inflammatory excess persisted over time or assess peripheral immune dysregulation broadly. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAlthough depression was strongly associated with high CRP levels, this association was no longer significant when analyses adjusted for the effects of early life stress.
“although depression was also strongly associated with high CRP levels, this association was no longer significant when analyses adjusted for the effects of early life stress”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Danese et al., 2008
Recent studies have found that depression and inflammation cluster in persons who experienced childhood adversity.
“Consistent with this possibility, recent studies have found that depression and inflammation cluster in persons who experienced childhood adversity.”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [14]
In the Dunedin cohort, depressed subjects who were negative for maltreatment were statistically indistinguishable from controls.
“However, depressed subjects who were negative for maltreatment were statistically indistinguishable from controls.”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [14]
In the Dunedin cohort, greater inflammation was also seen among subjects exposed to maltreatment alone.
“Greater inflammation was also seen among subjects exposed to maltreatment alone.”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [14]
In the Dunedin cohort, composite inflammation scores were higher among subjects with a maltreatment history and recent depression, relative to controls with neither.
“Composite scores were higher among subjects with a maltreatment history and recent depression, relative to controls with neither.”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [14]
Stimulated increases in proinflammatory cytokines were associated with sickness behavior symptoms resembling affective-cognitive and somatic symptoms of depression.
“Stimulated increases in proinflammatory cytokines were associated with symptoms such as fatigue, negative mood, anhedonia, cognitive impairment, social withdrawal, motor slowing – a variety of symptoms collectively referred to as sickness behavior and resembling those of affective-cognitive and somatic symptoms of depression (Dantzer et al., 2008; Eisenberger et al., 2010).”
From The interplay between stress, inflammation, and emotional attention: relevance for depression (2019) · cites this paper as Dantzer et al., 2008
Early life stress is a potential risk factor for inflammation-related depression.
“Potential risk factors include early life stress (Danese et al., 2008; Kuhlman et al., 2017)”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Danese et al., 2008
People with a history of childhood trauma tend to have higher adult inflammatory biomarkers and higher rates of depression.
“persons with a history of childhood trauma tend to have higher inflammatory biomarkers as adults and also exhibit higher rates of depression”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Danese et al., 2008
Inappropriate inflammation increases the risk and severity of mood disorders.
“This elevated inflammatory state has also been associated with increased risk and severity of mood disorders including depression (Aschbacher et al, 2012;Danese et al, 2008;Pace et al, 2012).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Danese et al, 2008
Increased inflammation is present not only in subjects who are depressed and have a history of childhood maltreatment but also in those who have experienced maltreatment but are not depressed.
“we showed that this increased inflammation is present not only in subjects who are depressed and have a history of childhood maltreatment but also in those who have experienced maltreatment but are not depressed (Danese et al., 2008)”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Danese et al., 2008
Individuals with maltreatment histories are reported to have elevated inflammation, elevated production of antibodies, compromised immune functioning, and poorer health compared to nonmaltreated individuals.
“individuals with maltreatment histories are reported to have elevated inflammation, elevated production of antibodies, compromised immune functioning, and poorer health compared to nonmaltreated individuals (Danese et al., 2008; Shirtcliff, Coe, & Pollak, 2009).”
From Associations Between Early Life Stress and Gene Methylation in Children (2015) · cites this paper as Danese et al., 2008
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Consistentz = 2.277reported p = .023 · recomputed p = .023
“z=2.277, p = .023”
- Consistentz = 2.451reported p = .014 · recomputed p = .014
“z=2.451, p = .014”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
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Insights Into Causal Pathways for Ischemic Heart Disease: Adverse Childhood Experiences Study
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The Lifelong Effects of Early Childhood Adversity and Toxic Stress
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“Interestingly, although depression was also strongly associated with high CRP levels, this association was no longer significant when analyses adjusted for the effects of early life stress (Danese et al., 2008).”
BackgroundInfluentialAdverse childhood experiences, allostasis, allostatic load and age-related disease
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“For example, maltreated individuals tend to have elevated inflammation levels (7, 9), which have been associated with recurrent depressive episodes (10) and poor treatment response (11).”
BackgroundInfluentialSelf-citationAllele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
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Self-citationImmune system to brain signaling: Neuropsychopharmacological implications
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“…with non-response to treatment with conventional antidepressant medications as well as early life stress, which is likewise associated with an antidepressant treatment non response (Sluzewska et al., 1997; Lanquillon et al., 2000; Nemeroff et al., 2003; Danese et al., 2007; Danese et al., 2008).”
BackgroundInflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications
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“…that may exhibit increased inflammation and that may be less responsive to standard antidepressant therapy, persons with a history of childhood trauma tend to have higher inflammatory biomarkers as adults and also exhibit higher rates of depression (Danese et al., 2007, Danese et al., 2008).”
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“…with a current major depression and a documented history of childhood maltreatment were over two times more likely to show high peripheral blood concentrations of high-sensitivity (hs) CRP (43 mg/l) compared with depressed individuals without a history of childhood abuse (Danese et al, 2008).”
BackgroundHeim, C., & Binder, E. B. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2011.10.032 · Cited by 986 · see citing works
“…include glucocorticoid resistance, increased levels of inflammation, increased central corticotropin-releasing hormone activity and decreased activity of the prosocial neuropeptide, oxytocin (for example, Carpenter et al., 2004; Danese et al., 2008, 2011; Heim et al., 2008a, 2009a, 2009b).”
CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies.
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“[11–13] These associations are in part due to (1) the ability of cytokines to sabotage and circumvent mechanisms of action of conventional antidepressant agents including cytokine effects on neurotransmitter function and synaptic plasticity (e.”
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“Among adults with major depression, those with a history of earlymaltreatment hadhigherCRP levels than thosewithout such a history (60).”
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“Promising avenues of research in this arena include gene–experience interaction,(44) the influence of early life experience on genomic expression (epigenetics),(45) and the role of inflammation.(46) The complex interplay of gene–environment interactions has been reviewed by an earlier study.”
BackgroundOsimo, E. F., Baxter, L. J., Lewis, G., Jones, P. B., & Khandaker, G. M. (2019) · Psychological Medicine · doi:10.1017/s0033291719001454 · Cited by 774 · see citing works
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BackgroundParadise lost: the neurobiological and clinical consequences of child abuse and neglect
Nemeroff, C. B. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.019 · Cited by 768 · see citing works
“Subsequently Danese, Pariente, and their colleagues (Danese et al., 2007, 2008) using the approximately 1,000 subjects in the Dunedin Multidisciplinary Health and Development Study reported that maltreated children exhibit a significant and graded increase in C-reactive protein (CRP) 20 years…”
BackgroundCalcia, M., Bonsall, D. R., Bloomfield, P. S., Selvaraj, S., Barichello, T., & Howes, O. D. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4218-9 · Cited by 710 · see citing works
“cytokines in childhood and are also associated with the high risk of mental illness in adulthood (Khandaker et al. 2014; Danese et al. 2008).”
BackgroundAdverse childhood experiences and life opportunities: shifting the narrative
Metzler, M., Merrick, M. T., Klevens, J., Ports, K. A., & Ford, D. C. (2017) · Children and Youth Services Review · doi:10.1016/j.childyouth.2016.10.021 · Cited by 713 · see citing works
“…factors that impact early brain development (McCrory, De Brito, & Viding, 2011; Shonkoff, Boyce, & McEwen, 2009; Shonkoff & Garner, 2012; Danese et al., 2008), the immune system (Bierhaus et al., 2003), and the endocrine system (Colborn, 2004; Roth, Lubin, Funk, & Sweatt, 2009; Szyf,…”
Nusslock, R., & Miller, G. E. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.017 · Cited by 672 · see citing works
“(92) stratified young adults into subgroups based upon a history of childhood maltreatment and past-year major depression.”
BackgroundCicchetti, D. (2013) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2012.02608.x · Cited by 653 · see citing works
“…have been shown to exhibit increased allostatic load in later life and this cumulative stress is associated with adverse emotional and physical health outcomes in adulthood (Danese et al., 2008; Dube et al., 2009; Felitti et al., 1998; Miller, Chen, & Parker, 2011; Wegman & Stetler, 2009).”
BackgroundAnnual Research Review: Suicide among youth – epidemiology, (potential) etiology, and treatment
Cha, C. B., Franz, P. J., M. Guzmán, E., Glenn, C. R., Kleiman, E. M., & Nock, M. K. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12831 · Cited by 602 · see citing works
“However, chronic early-life stress can result in reduced levels of cortisol, which may fail to suppress the body’s immune response, leading to increased inflammation (Danese et al., 2008).”
BackgroundMehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., Rex-Haffner, M., Loeschner, A., Gonik, M., Mercer, K. B., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217750110 · Cited by 548 · see citing works
“Proc Natl Acad Sci USA 104(4):1319–1324.”
BackgroundLippard, E. T. C., & Nemeroff, C. B. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19010020 · Cited by 527 · see citing works
Suglia, S. F., Koenen, K. C., Boynton-Jarrett, R., Chan, P. S., Clark, C. J., Danese, A., Faith, M. S., Goldstein, B. I., Hayman, L. L., Isasi, C. R., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000536 · Cited by 518 · see citing works
Self-citationTrauma exposure and stress-related disorders in inner city primary care patients
Gillespie, C. F., Bradley, B., Mercer, K., Smith, A. K., Conneely, K. N., Gapen, M., Weiss, T., Schwartz, A. C., Cubells, J. F., & Ressler, K. J. (2009) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2009.05.003 · Cited by 504 · see citing works
“The clinical and biological consequences of trauma exposure and neglect during youth and adulthood are well documented and substantially elevate adult risk formood and anxiety disorders [5–7,21,22], suicide attempt [6,21], substance abuse [6,21], unintended first pregnancy [23], systemic inflammation [24,25] and a var…”
BackgroundImmunoneuropsychiatry — novel perspectives on brain disorders
Pape, K., Tamouza, R., Leboyer, M., & Zipp, F. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0174-4 · Cited by 455 · see citing works
The Science of Early Life Toxic Stress for Pediatric Practice and Advocacy
Johnson, S. B., Riley, A. W., Granger, D. A., & Riis, J. L. (2013) · PEDIATRICS · doi:10.1542/peds.2012-0469 · Cited by 469 · see citing works
Zannas, A. S., Arloth, J., Carrillo-Roa, T., Iurato, S., Röh, S., Ressler, K. J., Nemeroff, C. B., Smith, A. K., Bradley, B., Heim, C., et al. (2015) · Genome Biology · doi:10.1186/s13059-015-0828-5 · Cited by 469 · see citing works
“themselves risk factors for such diseases [15, 16].”
Inflammation Effects on Motivation and Motor Activity: Role of Dopamine
Felger, J. C., & Treadway, M. T. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.143 · Cited by 453 · see citing works
“Subjects with a history of childhood trauma exhibit elevated inflammatory biomarkers and higher rates of depression as adults (Danese et al, 2008; Danese et al, 2007), and a ‘biological embedding’ or imprinting of stress through inflammatory processes in childhood has been proposed (Danese et al,…”
BackgroundCattaneo, A., Gennarelli, M., Uher, R., Breen, G., Farmer, A., Aitchison, K. J., Craig, I. W., Anacker, C., Zunsztain, P. A., McGuffin, P., et al. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.191 · Cited by 436 · see citing works
“…less responsive to antidepressant treatment, eg, depressed patients with a history of childhood trauma tend to have higher inflammatory biomarkers (Danese et al, 2008) and to be less responsive to pharmacological intervention (Nanni et al, 2012; Nemeroff et al, 2003); in this case, the increased…”
BackgroundMethodSelf-citationImaging the Role of Inflammation in Mood and Anxiety-related Disorders
Felger, J. C. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666171123201142 · Cited by 432 · see citing works
“Persons with a history of childhood trauma exhibit elevated inflammatory biomarkers and higher rates of depression as adults [58, 59], and a “biological embedding” or imprinting of stress through inflammatory processes in childhood has been proposed [60, 61].”
BackgroundChildhood maltreatment and inflammatory markers: a systematic review.
Coelho, R., Viola, T. W., Walss‐Bass, C., Brietzke, E., & Grassi‐Oliveira, R. (2014) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12217 · Cited by 426 · see citing works
“Second, although there were three longitudinal studies reviewed, they were all from the New Zealand birth-cohort (21, 35, 36).”
InfluentialAgnew‐Blais, J. C., & Danese, A. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00544-1 · Cited by 421 · see citing works
Self-citationKerker, B. D., Zhang, J., Nadeem, E., Stein, R. E. K., Hurlburt, M. S., Heneghan, A., Landsverk, J., & McCue Horwitz, S. (2015) · Academic Pediatrics · doi:10.1016/j.acap.2015.05.005 · Cited by 412 · see citing works
The Economics and Psychology of Inequality and Human DEvelopment
Cunha, F., & Heckman, J. J. (2009) · Journal of the European Economic Association · doi:10.1162/jeea.2009.7.2-3.320 · Cited by 407 · see citing works
“…adverse early environments on adult health.38 Nutritional deficiencies in early life cause lifelong health, cognitive, and personality problems.39 Danese et al. (2008) show that maltreatment in childhood has powerful negative effects on adult inflammation, a serious health risk.40 35Evidence on…”
Poulton, R., Moffitt, T. E., & Silva, P. A. (2015) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-015-1048-8 · Cited by 394 · see citing works
“This was followed by data showing elevated inflammation via C-reactive protein, fibrinogen, and white blood cell count in adult victims of child abuse [66, 67].”
Self-citationResilience in Development: Progress and Transformation
Masten, A. S., & Cicchetti, D. (2016) · Developmental Psychopathology · doi:10.1002/9781119125556.devpsy406 · Cited by 416 · see citing works
Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?
Danese, A., & J Lewis, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.198 · Cited by 393 · see citing works
“Furthermore, adults with a history of maltreatment showed elevated inflammation levels in the context of depression, daily stressors, or caregiving stress in later life compared to controls (Danese et al, 2008; Gouin et al, 2012; Kiecolt-Glaser et al, 2011).”
BackgroundInfluentialSelf-citationAgorastos, A., Pervanidou, P., Chrousos, G. P., & Baker, D. G. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00118 · Cited by 385 · see citing works
Pariante, C. M. (2017) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.04.001 · Cited by 382 · see citing works
“In subsequent reports, we showed that this increased inflammation is present not only in subjects who are depressed and have a history of childhood maltreatment but also in those who have experienced maltreatment but are not depressed (Danese et al., 2008); moreover, the increased inflammation clusters with metabolic…”
Self-citationDiet, Stress and Mental Health
Bremner, J. D., Moazzami, K., Wittbrodt, M. T., Nye, J. A., Lima, B. B., Gillespie, C. F., Rapaport, M. H., Pearce, B. D., Shah, A. J., & Vaccarino, V. (2020) · Nutrients · doi:10.3390/nu12082428 · Cited by 394 · see citing works
Zannas, A. S., Jia, M., Hafner, K., Baumert, J. J., Wiechmann, T., Pape, J. C., Arloth, J., Ködel, M., Martinelli, S., Roitman, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1816847116 · Cited by 342 · see citing works
“Because early life trauma is among the strongest risk factors for developing MDD (5), we further examined whether the effect of depression on age-related decrease in FKBP5 methylation is moderated by childhood trauma A”
Black sheep get the blues: a psychobiological model of social rejection and depression
Slavich, G. M., O’Donovan, A., Epel, E. S., & Kemeny, M. E. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.01.003 · Cited by 362 · see citing works
“Early maltreatment also predicts elevations in inflammation in adulthood (Danese et al., 2008).”
Genome-Wide Pharmacogenetics of Antidepressant Response in the GENDEP Project
Uher, R., Perroud, N. A., Ng, M., Hauser, J., Henigsberg, N., Maier, W., Mors, O. N., Placentino, A., Rietschel, M., Souery, D., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09070932 · Cited by 350 · see citing works
The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?
Misiak, B., Łoniewski, I., Marlicz, W., Frydecka, D., Szulc, A., Rudzki, L., & Samochowiec, J. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109951 · Cited by 343 · see citing works
Cytokines and Glucocorticoid Receptor Signaling
Pace, T. W. W., & Miller, A. H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04984.x · Cited by 339 · 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
“Childhood maltreatment predisposes to depression and may play a role in increasing the risk for inflammation in adulthood; 47,48 this has not been entered into the models, as these data were not available.”
BackgroundClustering of depression and inflammation in adolescents previously exposed to childhood adversity
Miller, G. E., & Cole, S. W. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.02.034 · Cited by 331 · see citing works
Childhood adversity and inflammatory processes in youth: a prospective study
Slopen, N., Kubzansky, L. D., McLaughlin, K. A., & Koenen, K. C. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.05.013 · Cited by 330 · see citing works
Teicher, M. H., Gordon, J. B., & Nemeroff, C. B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01367-9 · Cited by 325 · see citing works
“, inflammation [1, 67, 68], HPA axis disturbance [64, 86], dysfunctional neuroanatomic circuits [4, 87], abnormal neural activity [88– 91], and neurotransmitter dysfunction [92–94]) as well as a host of critical clinical risk factors such as inadequate response to antidepressants [3].”
BackgroundEffect of childhood physical abuse on cortisol stress response
Carpenter, L. L., Shattuck, T. T., Tyrka, A. R., Geracioti, T. D., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2007-4 · Cited by 307 · see citing works
“In addition to neurohormonal dysregulation, early life stress in the form of maltreatment may mediate changes in immune function, as evidenced by elevated levels of inflammatory markers (Danese et al. 2008).”
Zunszain, P. A., Hepgul, N., & Pariante, C. M. (2012) · Current topics in behavioral neurosciences · doi:10.1007/7854_2012_211 · Cited by 317 · see citing works
Self-citationBiological embedding of stress through inflammation processes in childhood
Danese, A., Caspi, A., Williams, B., Ambler, A., Sugden, K., Mika, J., Werts, H., Freeman, J., Pariante, C. M., Moffitt, T. E., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.5 · Cited by 301 · see citing works
Self-citationLeveraging the biology of adversity to address the roots of disparities in health and development
Shonkoff, J. P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121259109 · Cited by 307 · see citing works
Associations Between Early Life Stress and Gene Methylation in Children
Romens, S. E., McDonald, J., Svaren, J., & Pollak, S. D. (2015) · Child Development · doi:10.1111/cdev.12270 · Cited by 299 · see citing works
“In fact, individuals with maltreatment histories are reported to have elevated inflammation, elevated production of antibodies, compromised immune functioning, and poorer health compared to nonmaltreated individuals (Danese et al., 2008; Shirtcliff, Coe, & Pollak, 2009).”
BackgroundHidden wounds? inflammatory links between childhood trauma and psychopathology
Danese, A., & Baldwin, J. R. (2017) · Annual Review of Psychology · doi:10.1146/annurev-psych-010416-044208 · Cited by 286 · see citing works
“Finally, depressed individuals with a history of childhood maltreatment show both elevated unstimulated inflammation levels (Danese et al. 2008) and greater inflammatory responses to acute psychosocial stress (Pace et al.”
BackgroundInfluentialSelf-citationChildhood bullying involvement predicts low-grade systemic inflammation into adulthood
Copeland, W. E., Wolke, D., Lereya, S. T., Shanahan, L., Worthman, C., & Costello, E. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323641111 · Cited by 291 · see citing works
“The finding of greater increases in CRP levels for pure victims is less surprising given previous evidence of short- and long-term impaired health functioning (1, 6, 8) and associations between childhood psychosocial adversity and inflammation levels (27, 28).”
BackgroundBrain microglia in psychiatric disorders
Mondelli, V., Vernon, A. C., Turkheimer, F., Dazzan, P., & Pariante, C. M. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30101-3 · Cited by 262 · see citing works
Self-citationPolanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A., Sugden, K., Uher, R., Poulton, R., & Moffitt, T. E. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.114 · Cited by 285 · see citing works
Self-citationThe molecular bases of the suicidal brain
Turecki, G. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3839 · Cited by 281 · see citing works
Miller, A. H. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.08.006 · Cited by 261 · see citing works
“, 2007), and depressed patients with early life stress appear to be especially likely to exhibit increased innate immune responses at baseline and following stress (Danese et al., 2008; Pace et al., 2006).”
Buss, C., Entringer, S., Moog, N. K., Toepfer, P., Fair, D. A., Simhan, H. N., Heim, C. M., & Wadhwa, P. D. (2017) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2017.03.001 · Cited by 250 · see citing works
Computational identification of gene–social environment interaction at the human <i>IL6</i> locus
Cole, S. W., Arevalo, J. M. G., Takahashi, R., Sloan, E. K., Lutgendorf, S. K., Sood, A. K., Sheridan, J. F., & Seeman, T. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911515107 · Cited by 256 · see citing works
A Developmental Psychopathology Perspective on Child Maltreatment
Toth, S., & Cicchetti, D. (2013) · Child Maltreatment · doi:10.1177/1077559513500380 · Cited by 277 · see citing works
The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)
Raison, C. L., & Miller, A. H. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.2 · Cited by 253 · see citing works
Microbial ‘Old Friends’, immunoregulation and stress resilience
Rook, G. A. W., Lowry, C. A., & Raison, C. L. (2013) · Evolution Medicine and Public Health · doi:10.1093/emph/eot004 · Cited by 245 · see citing works
Adverse childhood experiences and risk of type 2 diabetes: A systematic review and meta-analysis
Huang, H., Yan, P., Shan, Z., Chen, S., Li, M., Luo, C., Gao, H., Hao, L., & Liu, L. (2015) · Metabolism · doi:10.1016/j.metabol.2015.08.019 · Cited by 239 · see citing works
“[19] Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A.”
BackgroundInflammation in Children and Adolescents With Neuropsychiatric Disorders: A Systematic Review
Mitchell, R. H. B., & Goldstein, B. I. (2013) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.11.013 · Cited by 241 · see citing works
The Neurobiological Toll of Child Abuse and Neglect
Neigh, G. N., Gillespie, C. F., & Nemeroff, C. B. (2009) · Trauma Violence & Abuse · doi:10.1177/1524838009339758 · Cited by 240 · see citing works
“ELS exposure increases the incidence of systemic inflammation (Danese, Pariante, Caspi, Taylor, & Poulton, 2007; Danese et al., 2008) and a variety of medical illnesses, including obesity (Felitti et al.”
BackgroundMoffitt, T. E., & Tank, T. K.-G. 2. T. (2013) · Development and Psychopathology · doi:10.1017/s0954579413000801 · Cited by 239 · see citing works
“Moreover, some research suggests that violence exposure has its greatest effects on future health among the subset of violence-exposed individuals who develop mental disorders following violence exposure (Danese et al., 2008, 2011; Heim et al., 2000; Vythilingam et al., 2002).”
BackgroundSelf-citationEarly adversity and adult health outcomes
Taylor, S. E., Way, B. M., & Seeman, T. E. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000411 · Cited by 235 · see citing works
Bufalino, C., Hepgul, N., Aguglia, E., & Pariante, C. M. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.04.009 · Cited by 228 · see citing works
Self-citationDanger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders
Fleshner, M., Frank, M., & Maier, S. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.125 · Cited by 216 · see citing works
Poverty Grown Up: How Childhood Socioeconomic Status Impacts Adult Health
Conroy, K., Sandel, M. T., & ZUCKERMAN, B. S. (2010) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e3181c21a1b · Cited by 223 · see citing works
Antidepressant therapies inhibit inflammation and microglial M1-polarization
Kalkman, H. O., & Feuerbach, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.001 · Cited by 212 · see citing works
Imaging phenotypes of major depressive disorder: genetic correlates
Savitz, J. B., & Drevets, W. C. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.03.082 · Cited by 216 · see citing works
Serum and gene expression profile of cytokines in first-episode psychosis
Di Nicola, M., Cattaneo, A., Hepgul, N., Di Forti, M., Aitchison, K. J., Janiri, L., Murray, R. M., Dazzan, P., Pariante, C. M., & Mondelli, V. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.06.010 · Cited by 217 · see citing works
“This notion is consistent with our previous studies finding an association between a history of childhood trauma and peripheral inflammation in adults (Danese et al., 2007, 2008) as well as children (Danese et al., 2010).”
ResultSelf-citationEnduring psychobiological effects of childhood adversity
Ehlert, U. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.06.007 · Cited by 213 · see citing works
“Additional analyses showed that the association between childhood maltreatment and elevated CRP levels was particularly strong among individuals with current depression (Danese et al., 2008).”
BackgroundChild maltreatment and the development of substance use and disorder
Cicchetti, D., & Handley, E. D. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.100144 · Cited by 210 · see citing works
Microbial ‘old friends’, immunoregulation and socioeconomic status
Rook, G. A. W., Raison, C. L., & Lowry, C. A. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12269 · Cited by 207 · see citing works
Intergenerational transmission of maltreatment and psychopathology: the role of antenatal depression
Plant, D. T., Barker, E. D., Waters, C. S., Pawlby, S., & Pariante, C. M. (2013) · Psychological Medicine · doi:10.1017/s0033291712001298 · Cited by 201 · see citing works
“This threshold has previously been identified as a valid index of childhood maltreatment (Danese et al. 2008).”
BackgroundSelf-citationGenes, Environments, and Time: The Biology of Adversity and Resilience
Boyce, W. T., Levitt, P. R., Martínez, F. D., McEwen, B. S., & Shonkoff, J. P. (2021) · PEDIATRICS · doi:10.1542/peds.2020-1651 · Cited by 212 · see citing works
McIntyre, R. S., Subramaniapillai, M., Lee, Y., Pan, Z., Carmona, N. E., Shekotikhina, M., Rosenblat, J. D., Brietzke, E., Soczynska, J. K., Cosgrove, V. E., et al. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.0779 · Cited by 200 · see citing works
“Daily cigarette smoking 8 (27) 6 (21) .”
The interplay between stress, inflammation, and emotional attention: relevance for depression
Maydych, V. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00384 · Cited by 193 · see citing works
Roque, A., Ochoa‐Zarzosa, A., & Torner, L. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.09.017 · Cited by 190 · 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
“Indeed, there is evidence that inflammation moderates the association between childhood maltreatment and risk of depression in adulthood (Danese et al. 2008).”
BackgroundModulatory effects of α7 nAChRs on the immune system and its relevance for CNS disorders
Kalkman, H. O., & Feuerbach, D. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2175-4 · Cited by 182 · see citing works
“Inflammation and exposure to stress are generally recognized as strong proximal factors for the development of depression symptoms [109].”
BackgroundAlt, S. R., Turner, J. D., Klok, M. D., Meijer, O. C., Lakke, E. A. J. F., DeRijk, R. H., & Muller, C. P. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.09.001 · Cited by 184 · see citing works
“On the other hand, the incidence of childhood abuse is highly variable in depressed patients, ranging from 4% to 12% (Danese et al., 2008), 13% (Mullen et al.”
BackgroundInflammatory cytokine-associated depression
Lotrich, F. E. (2015) · Brain Research · doi:10.1016/j.brainres.2014.06.032 · Cited by 183 · see citing works
The biology of depression in cancer and the relationship between depression and cancer progression
Sotelo, J. L., Musselman, D. L., & Nemeroff, C. B. (2014) · International Review of Psychiatry · doi:10.3109/09540261.2013.875891 · Cited by 180 · see citing works
“…to the age of 32, those with current major depression and a history of childhood maltreatment were over twice as likely to exhibit elevated peripheral blood concentrations of high sensitivity CRP ( 3 mg/L) compared with equally depressed individuals without a history of abuse (Danese et al., 2008).”
BackgroundDooley, L. N., Kuhlman, K. R., Robles, T. F., Eisenberger, N. I., Craske, M. G., & Bower, J. E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.006 · Cited by 176 · see citing works
“Following the summary of the kynurenine pathway in the previous paragraph, QUIN and glutamate released by activated microglia operate synergistically to promote excitotoxicity (Dantzer and Walker, 2014).”
Is there a role for immune-to-brain communication in schizophrenia?
Khandaker, G. M., & Dantzer, R. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3975-1 · Cited by 169 · see citing works
“Furthermore, evidence from the Dunedin birth cohort suggests higher levels of CRP mediate the association between childhood maltreatment and risk of depression in adulthood (Danese et al. 2008).”
BackgroundRogosch, F. A., Dackis, M. N., & Cicchetti, D. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000587 · Cited by 170 · see citing works
“We also are currently collecting C-reactive protein as a biomarker of immune functioning (i.e., inflammation; cf. Danese et al., 2008).”
Boer, M. M. B.-D., van Wetten, M.-L., & Pruimboom, L. (2012) · Nutrition & Metabolism · doi:10.1186/1743-7075-9-32 · Cited by 166 · see citing works
“Factors such as stress endured early in life, trauma and polymorphisms are possible risk factors for loss of GR and catecholamine sensitivity [33-35].”
BackgroundBiomarkers of adverse childhood experiences: A scoping review
Deighton, S., Neville, A., Pusch, D., & Dobson, K. S. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.08.097 · Cited by 165 · see citing works
“All 14 studies showed a link between ACEs and greater inflammation (Bertone-Johnson et al., 2012; Carpenter et al., 2010; Crosswell et al., 2014; Danese et al., 2008, 2007; Hostinar et al., 2015; Kiecolt-Glaser et al., 2011; Li et al., 2015; Matthews et al., 2014; Rooks et al., 2012; Schrepf et…”
Inflammation Models of Depression in Rodents: Relevance to Psychotropic Drug Discovery
Remus, J. L., & Dantzer, R. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw028 · Cited by 166 · see citing works
“…depression are now reported to have elevated levels of inflammatory markers, including proinflammatory cytokines (Kim et al., 2008; Shelton and Claiborne, 2010), C-reactive protein (Danese et al., 2008; Vogelzangs et al., 2012; Morris et al., 2014), and myeloperoxidase (Vaccarino et al., 2008).”
Background
- Authors
- Danese, A., Moffitt, T. E., Pariante, C. M., Ambler, A., Poulton, R., & Caspi, A.
- Affiliations
- King's College London (GB)
- Duke University (US)
- University of Otago (NZ)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2008-04-01
- Volume
- 65
- Issue
- 4
- Pages
- 409
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC2923056
- OpenAlex
- W2138970660
- Cited by
- 641
- References
- 37
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 16 · 2023: 26 · 2022: 32 · 2021: 41 · 2020: 39 · 2019: 56 · 2018: 48 · 2017: 37 · 2016: 49 · 2015: 54 · 2014: 37 · 2013: 41 · 2012: 39
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (080276, 58408)
- National Institute of Mental Health (MH-49414, MH-077874, MH 45070, R01MH049414, R01MH077874, R01MH045070)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, child abuse, inflammation, C-reactive protein, fibrinogen, leukocytes, cardiovascular risk, Dunedin Multidisciplinary Health and Development Study, birth cohort
- MeSH terms
- Adult, C-Reactive Protein, Child, Child Abuse, Child, Preschool, Depressive Disorder, Major, Major Depressive Disorder, Female, Follow-Up Studies, Humans, Inflammation, Male, Prospective Studies, Smoking, Cohort Studies, Biomarkers, Parenting, Sex Distribution, Diagnostic and Statistical Manual of Mental Disorders
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-02.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-02.
Statistics and arithmetic are recomputed, not judged.
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