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Cited by 210Tryptophan and brain disordersSuicide and Self-Harm StudiesTreatment of Major Depression

SUICIDAL IDEATION IS ASSOCIATED WITH ELEVATED INFLAMMATION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: Research Article: Suicidal Ideation and Inflammation

Open access
O'Donovan, Aoife, Rush, Gavin, Hoatam, Gerard, Hughes, Brian M., McCrohan, AnnMaria, Kelleher, Cecily, O'Farrelly, Cliona, Malone, Kevin M.·2013·Depression and Anxiety
DOI 10.1002/da.22087
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Abstract

BACKGROUND: Patients with major depressive disorder (MDD) who attempt or complete suicide have elevated inflammation compared to nonsuicidal patients with MDD. However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers. METHODS: To clarify, we measured inflammatory markers in patients with MDD with and without high levels of suicidal ideation and in nondepressed controls (N = 124). Levels of suicidal ideation, depression severity, and recent suicide attempts were assessed by structured clinical interviews. A composite score including the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) was used as an inflammatory index. Analysis of covariance models were used to assess group differences with adjustments for age and gender. RESULTS: Patients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η(2) = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial η(2) = .15, P = .009. In contrast, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52, partial η(2) = .01, P = .47. Follow-up analyses indicated that differences between patients with MDD and high versus lower suicidal ideation were independent of depression severity and recent suicide attempts. CONCLUSIONS: Suicidal ideation may be uniquely associated with inflammation in depressed patients.

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Crossref · 10.1002/da.22087

Cites

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Claims the paper makes

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  • Findingown data

    Patients with major depressive disorder and lower suicidal ideation were not significantly different from controls on the inflammatory index.

    “In contrast, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52,partial η 2 = .01,P = .47.”
    • Also stated in: § SUICIDAL IDEATION AND INFLAMMATION · plain
      “However, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52,partial η 2 = .01,P = .47.”
    Quote in the paperSubstantial claim
  • Findingown data

    Differences between patients with major depressive disorder and high versus lower suicidal ideation in inflammatory index were independent of depression severity and recent suicide attempts.

    “Follow-up analyses indicated that differences between patients with MDD and high versus lower suicidal ideation were independent of depression severity and recent suicide attempts.”
    Quote in the paperSubstantial claim
  • Findingown data

    Patients with major depressive disorder and high suicidal ideation had significantly higher inflammatory index scores than controls.

    “Patients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η 2 = .25,P < .001”
    • Also stated in: § SUICIDAL IDEATION AND INFLAMMATION · plain
      “Patients with high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η 2 = .25,P < .001”
    Quote in the paperSubstantial claim
  • Findingown data

    Patients with major depressive disorder and high suicidal ideation had significantly higher inflammatory index scores than patients with major depressive disorder and lower suicidal ideation.

    “and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial η 2 = .15,P = .009.”
    • Also stated in: § SUICIDAL IDEATION AND INFLAMMATION · plain
      “and patients with MDD and lower levels of suicidal ideation, F(1,44) = 7.59, partial η 2 = .15,P = .009.”
    Quote in the paperSubstantial claim
  • Findingown data

    There were no significant group differences in TGF-β in any of the contrasts.

    “Results indicated no significant group differences in TGF-β in any of the contrasts.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 44

  • May combine two claims.

    Findingown data

    Principal components analysis revealed that TNF-α, IL-6, IL-10, and CRP had loadings greater than .40 on a single factor, but the loading for TGF-β was less than .40.

    “Principal components analysis revealed that TNF-α, IL-6, IL-10, and CRP had loadings greater than .40 on a single factor (range: .49-.69), but that the loading for TGF-β was less than .40 at -.29.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    The results appeared independent of the duration of antidepressant treatment and of the presence versus absence of anti-inflammatory treatments.

    “Although our results appeared independent of duration of antidepressant treatment and presence versus absence of anti-inflammatory treatments”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the small number of participants in whom ACTH and cortisol were measured, there was no evidence of differences between groups, giving no support to HPA axis dysregulation as an explanation for the observed group differences in inflammation.

    “In the small number of participants for whom we measured ACTH and cortisol, we found no evidence for differences between groups and, thus, no support for the hypothesis that HPA axis dysregulation contributed to the observed group differences in inflammation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among the three groups, there were no significant differences in gender.

    “but not gender (χ 2 = .72,P = .70)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among participants with major depressive disorder, there were no group differences in duration of antidepressant treatment.

    “duration of antidepressant treatment (t = .56,P = .58)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among participants with major depressive disorder, there were no group differences in gender.

    “but there were no group differences in gender (χ 2 = .71,P = .40)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among participants with major depressive disorder, there were no group differences in use of anti-inflammatory medications.

    “or use of anti-inflammatory medications (χ 2 = .89,P = .34).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In this sample, patients who had attempted suicide in the past month did not differ significantly from other MDD patients on any inflammatory marker, including the inflammatory index (t = .42, P = .68), IL-6 (t = .40, P = .69) and CRP (t = .87, P = .38).

    “Results indicated no significant differences between suicide attempters and nonattempters on any of the inflammatory markers, including the inflammatory index (t = .42,P = .68),IL-6 (t = .40,P = .69),and CRP (t = .87,P = .38).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among participants with major depressive disorder, there were no group differences in number of episodes of depression experienced.

    “number of episodes of depression experienced (t = .73,P = .47)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Cortisol and ACTH were significantly and positively associated with one another.

    “Cortisol and ACTH were significantly and positively associated with one another (r = .61,P < .001)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among the three groups, there were no significant differences in body mass index.

    “BMI (F(2,92) = .85,P = .43)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neither cortisol nor ACTH was significantly associated with any of the inflammatory markers.

    “but neither of these was significantly associated with any of the inflammatory markers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Older individuals had significantly higher scores on the inflammatory index.

    “Older individuals had significantly higher scores on the inflammatory index (r = .37,P = .001)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among participants with major depressive disorder, there were no group differences in estimated duration of major depressive disorder in years.

    “estimated duration of MDD in years (t = .35,P = .73)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among the three groups, there were significant differences in age.

    “Among the three groups, there were significant differences in age (F(2,119) = 3.93, P = .02)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among the three groups, there were no significant differences in use of anti-inflammatory medications.

    “or use of anti-inflammatory medications (χ 2 = 1.92,P = .38).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There was a trend toward lower scores on the inflammatory index in women.

    “and there was a trend toward lower scores on the inflammatory index in women (t = 1.65,P = .10).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among participants with major depressive disorder, those with high levels of suicidal ideation were significantly older than those with lower levels of suicidal ideation.

    “Among participants with MDD, those with high levels of suicidal ideation were significantly older than those with lower levels of suicidal ideation (t = 2.04, P = .04)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was a trend toward higher levels of C-reactive protein in patients with major depressive disorder but this was not statistically significant.

    “There was also a trend toward higher levels of CRP in patients with MDD but this was not statistically significant, F(1,88) = 3.21, partial η 2 = .03,P = .08”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    All of the inflammatory markers were positively associated with one another, with the exception of TGF-β, which was negatively associated with the other inflammatory markers.

    “All of the inflammatory markers were positively associated with one another (r range: .31-.02, P range: .001-.89), with the exception of TGF-β, which was negatively associated with the other inflammatory markers”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among participants with major depressive disorder, there were no group differences in body mass index.

    “BMI (t = .76,P = .45)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Suicidal depression is characterized by hopelessness and negative expectations for the future, which have previously been associated with elevated inflammation.

    “Suicidal depression is characterized by hopelessness and negative expectations for the future, which have previously been associated with elevated inflammation.[20,21]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] MacLeod, 2005, Hopelessness and positive and negative future thinking in parasuicide, Br J Clin Psychol source

      Not checked in the free run.

    • cites [21] O'Donovan, 2009, Pessimism correlates with leukocyte telomere shortness and elevated interleukin-6 in post-menopausal women, Brain Behav Immun source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The mean inter- and intra-assay coefficients of variation were less than 9% for ACTH and cortisol.

    “The mean inter-and intra-assay coefficients of variation were <9% for ACTH for cortisol.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The Hamilton Rating Scale for Depression had acceptable reliability in the sample, with Cronbach's alpha of .91.

    “The scale had acceptable reliability in our sample (Cronbach's α = .91).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Inflammatory responses to acute stress in the laboratory are exaggerated in depressed individuals, indicating that depression may also increase inflammation by promoting greater inflammatory responses to everyday stress.

    “Additionally, inflammatory responses to acute stress in the laboratory are exaggerated in depressed individuals, indicating that depression may also increase inflammation by promoting greater inflammatory responses to everyday stress.[16,17]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Miller, 2005, Clinical depression and regulation of the inflammatory response during acute stress, Psychosom Med source

      Not checked in the free run.

    • cites [17] Pace, 2006, Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress, Am J Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    All samples were assayed in duplicate and the coefficients of variation for these assays were less than 12%.

    “All samples were assayed in duplicate and the coefficients of variation for these assays were <12%.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Numerous studies have documented hypothalamic-pituitary-adrenal axis abnormalities in major depressive disorder.

    “and numerous studies have documented HPA axis abnormalities in MDD.[30]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Pariante, 2008, The HPA axis in major depression: classical theories and new developments, Trends Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Humans treated for cancer and hepatitis C with high doses of pro-inflammatory cytokines demonstrate depression symptoms and are at high risk for developing major depressive disorder.

    “Humans who are treated for cancer and hepatitis C with high doses of pro-inflammatory cytokines also demonstrate these symptoms and are at high risk for developing MDD.[12,13]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [12] Capuron, 2001, Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [13] Capuron, 2002, Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions, Neuropsychopharmacology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The Mini International Neuropsychiatric Instrument suicidal ideation scale had acceptable reliability in the sample, with Cronbach's alpha of .88.

    “The scale had acceptable reliability in our sample (Cronbach's α = .88).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The Mini International Neuropsychiatric Instrument has high diagnostic concordance with the Structured Clinical Interview for DSM-IV.

    “which has high diagnostic concordance with the Structured Clinical Interview for DSM-IV.[31]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Sheehan, 1998, The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10, J Clin Psychiatry

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Inflammation may be elevated in only a subset of depressed patients.

    “and inflammation may be elevated in only a subset of depressed patients.[9]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Glassman, 2007, Where there is depression, there is inflammation… sometimes!, Biol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisereasoning

    Suicide attempts may be associated with high levels of physical trauma, which could in itself have strong influences on systemic inflammatory markers.

    “A complication in the interpretation of these studies is that suicide attempts may be associated with high levels of physical trauma, which could in itself have strong influences on systemic inflammatory markers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In another large-scale prospective study of healthy adults, depressive symptoms predicted levels of inflammation 6 years later whereas inflammation did not predict depressive symptoms.

    “Moreover, in another large-scale prospective study of healthy adults, depressive symptoms predicted levels of inflammation 6 years later whereas inflammation did not likewise predict depressive symptoms.[15]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Stewart, 2009, A prospective evaluation of the directionality of the depression-inflammation relationship, Brain Behav Immun source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Greater severity of depression and the medical lethality of suicide attempts could account for elevated inflammation in suicide attempters and completers.

    “However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Clinical interviewers were trained and calibrated.

    “Trained and calibrated clinical interviewers administered structured clinical interviews within 24 hr of the blood draw”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It is well-established that the hypothalamic-pituitary-adrenal axis exerts important regulatory influences on inflammation.

    “It is well-established that the hypothalamicpituitary-adrenal (HPA) axis exerts important regulatory influences on inflammation [29]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Chrousos, 1995, The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation, N Engl J Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some studies have failed to find an association between depression and inflammation.

    “and some studies have failed to find an association between depression and inflammation.[7][8][9]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] O'Donovan, 2010, Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships, Brain Behav Immun source

      Not checked in the free run.

    • cites [8] Whooley, 2007, Depression and inflammation in patients with coronary heart disease: findings from the Heart and Soul Study, Biol Psychiatry source

      Not checked in the free run.

    • cites [9] Glassman, 2007, Where there is depression, there is inflammation… sometimes!, Biol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Particularly strong evidence implicates inflammation in the development of depressive symptoms and major depressive disorder.

    “Particularly strong evidence implicates inflammation in the development of depressive symptoms and major depressive disorder (MDD).[4][5][6]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [4] Maes, 1995, Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression, J Affect Disord source

      Not checked in the free run.

    • cites [5] Alesci, 2005, Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [6] Hestad, 2003, Raised plasma levels of tumor necrosis factor alpha in patients with depression: normalization during electroconvulsive therapy, J ECT source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Emerging evidence indicates that some anti-inflammatory treatments may antagonize the effects of commonly used antidepressants, including selective serotonin reuptake inhibitors.

    “emerging evidence indicates that some anti-inflammatory treatments may antagonize the effects of commonly used antidepressant treatments including selective serotonin reuptake inhibitors.[44]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Warner-Schmidt, 2011, Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by anti-inflammatory drugs in mice and humans, Proc Natl Acad Sci USA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Kynurenine levels are elevated in patients with MDD with a history of a suicide attempt compared with those without such a history.

    “One previous report suggested that levels of kynurenine, which can be stimulated by inflammation, are elevated in patients with MDD with versus without a history of a suicide attempt.[36]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Sublette, 2011, Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder, Brain Behav Immun source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Kynurenine is thought to play a key role in inflammation-associated depression.

    “Kynurenine, in turn, is thought to play a key role in inflammation-associated depression.[3]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Dantzer, 2008, From inflammation to sickness and depression: when the immune system subjugates the brain, Nat Rev Neurosci source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Analysis of covariance models were used to assess group differences with adjustments for age and gender.

    “Analysis of covariance models were used to assess group differences with adjustments for age and gender.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Cortisol generally has anti-inflammatory effects.

    “cortisol in turn generally has anti-inflammatory effects.[29]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Chrousos, 1995, The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation, N Engl J Med source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Follow-up analyses additionally controlled for depression severity and suicide attempts in analyses including only patients with major depressive disorder.

    “and additionally controlling for depression severity and suicide attempts in follow-up analyses including only patients with MDD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Suicidal ideation may promote inflammation in patients with MDD, and inflammation may in turn exacerbate depressive symptoms.

    “Thus, suicidal ideation may promote inflammation in patients with MDD, and inflammation in turn may exacerbate depressive symptoms.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Acute threat exposure is associated with increased HPA axis activity, indexed by higher cortisol levels.

    “Acute threat exposure is associated with increased HPA axis activity as indexed by higher levels of cortisol, [23]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Dickerson, 2004, Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research, Psych Bull source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Levels of inflammatory markers are elevated in the brains of suicide completers.

    “a previous report suggesting that levels of inflammatory markers are elevated in the brains of suicide completers.[25]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Tonelli, 2008, Elevated cytokine expression in the orbitofrontal cortex of victims of suicide, Acta Psychiatr Scand source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    Circulating basal levels of ACTH and cortisol do not give complete information about HPA axis activity, because the axis operates through feedback loops involving protein and receptor expression.

    “circulating basal levels of ACTH and cortisol do not provide complete information on activity of the HPA axis, which functions through feedback loops involving the expression of proteins as well as receptors.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous research shows that suicide attempters have higher levels of inflammatory markers than comparison participants without a history of suicide attempts.

    “previous research showing that suicide attempters have higher levels of inflammatory markers than comparison participants without a history of suicide attempts.[26,27]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [26] Janelidze, 2011, Cytokine levels in the blood may distinguish suicide attempters from depressed patients, Brain Behav Immun source

      Not checked in the free run.

    • cites [27] Lindqvist, 2009, Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hopelessness and perceived psychological stress may promote inflammation in suicidal individuals.

    “In particular, hopelessness and perceived psychological stress may promote inflammation in suicidal individuals.[22,23,37]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [22] Dickerson, 2009, Social-evaluative threat and proinflammatory cytokine regulation: an experimental laboratory investigation, Psychol Sci source

      Not checked in the free run.

    • cites [23] Dickerson, 2004, Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research, Psych Bull source

      Not checked in the free run.

    • cites [37] Blascovich, 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    One plausible explanation for the findings is that suicidal ideation is more common in individuals with inflammation-associated depression.

    “one plausible explanation for our findings is that suicidal ideation is more common in individuals with inflammation-associated depression.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Dantzer, 2008, From inflammation to sickness and depression: when the immune system subjugates the brain, Nat Rev Neurosci source

      Not checked in the free run.

    • cites [35] Maes, 2011, Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression, Prog Neuropsychopharmacol Biol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Suicidal ideation in and of itself may promote inflammation in depressed patients.

    “Another potential explanation is that suicidal ideation in and of itself promotes inflammation in depressed patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    A dysregulated HPA axis could play a role in the relationship between suicidal ideation and inflammation.

    “Thus, a dysregulated HPA axis could play a role in the relationship between suicidal ideation and inflammation.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [23] Dickerson, 2004, Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research, Psych Bull source

      Not checked in the free run.

    • cites [29] Chrousos, 1995, The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Suicidal depressed patients may be at increased risk for inflammatory disorders, including chronic diseases of aging, and may benefit from treatments targeting inflammation and psychological stress.

    “the data suggest that suicidal depressed patients may be at increased risk for inflammatory disorders including chronic diseases of aging and may benefit from treatments targeting inflammation and psychological stress.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Depression severity was measured with a structured interview (HAM-D), and results might have differed had a self-report measure been used.

    “we used a structured interview measure of depression severity (HAM-D) and results may have been different if we had employed a self-report measure.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    Patients were hospital in-patients taking antidepressant and other psychotropic medications, and some were using anti-inflammatory medications, all of which could have influenced the dependent variables.

    “Second, patients in our study were hospital in-patients taking antidepressant and other psychotropic medications and some participants were using anti-inflammatory medications, all of which could have influenced levels of our dependent variables.[38]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Hiles, 2012, Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis, Psychol Medicine

      Not checked in the free run.

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  • The paper relies on this without support.

    Little is known about the relationship between suicidal ideation and inflammation in individuals without comorbid physical diseases.

    “However, little is known about the relationship between suicidal ideation and inflammation in individuals without comorbid physical diseases.”
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Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Greater suicidal ideation severity is associated with higher CRP, IL-6, and IL-10 levels and with activated microglia-related alterations of the tryptophan-kynurenine pathway.

    “Greater suicidal ideation severity is associated with higher CRP (197), IL-6, and IL-10 levels (215) and with activated microglia-related alterations of the tryptophan-kynurenine pathway (216).”

    From A brain-centric model of suicidal behavior (2020) · cites this paper as [215]

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.

  • ConsistentF(2, 119) = 3.93reported p = .02 · recomputed p = .022

    “F(2,119) = 3.93, p = .02”

  • ConsistentF(2, 92) = 0.85reported p = .43 · recomputed p = .431

    “F(2,92) = .85,p = .43”

2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • High-suicidal-ideation patients are described as older, but Table 1 shows the reverse

    Major

    The text says patients with high suicidal ideation were older than those with lower suicidal ideation. Table 1 reports mean ages of 47.00 and 54.09, respectively.

  • The direction of the IL-10 comparison with controls changes

    Major

    The results describe a trend toward lower IL-10 in high-suicidal-ideation patients than in controls, whereas the discussion describes a trend toward higher IL-10 for the same comparison.

  • The cutoff for high suicidal ideation is defined two ways

    Minor

    The measures section includes patients scoring exactly 10 in the high-suicidal-ideation group, while the data-analysis section defines that group as scoring greater than 10.

3 of 3

Cites

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Cited by

Sorted by citations

Related

Authors
O'Donovan, A., Rush, G., Hoatam, G., Hughes, B. M., McCrohan, A., Kelleher, C., O'Farrelly, C., & Malone, K. M.
Affiliations
  • St. Patrick's Hospital (IE)
  • Creighton University (US)
  • Ollscoil na Gaillimhe – University of Galway (IE)
  • St. Vincent's University Hospital (IE)
  • University College Dublin (IE)
  • School of Biochemistry and Immunology; Trinity College; Dublin; Ireland
ORCID
Venue
Depression and Anxiety
Publisher
Wiley
Published
2013-03-15
Volume
30
Issue
4
Pages
307-314
ISSN
1091-4269 (ISSN-L)
DOI
10.1002/da.22087
OpenAlex
W2115679410
Semantic Scholar
6191895575d451338dbe8477cac354caf3620f1d
Cited by
210
References
42
Citations by year
2026: 9 · 2025: 14 · 2024: 18 · 2023: 12 · 2022: 19 · 2021: 24 · 2020: 19 · 2019: 14 · 2018: 15 · 2017: 20 · 2016: 10 · 2015: 19 · 2014: 12 · 2013: 4
FWCI
5.07
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 900 d)
Locations
  • Depression and Anxiety (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
H. Lundbeck A/S
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
suicidal ideation, major depressive disorder, inflammation, inflammatory markers, TNF-α, interleukin-6, IL-10, C-reactive protein, depression severity, suicide attempts, inflammatory indices
MeSH terms
Adult, Analysis of Variance, C-Reactive Protein, Major Depressive Disorder, Female, Humans, Inflammation, Male, Middle Aged, Severity of Illness Index, Suicide, Attempted, Tumor Necrosis Factor-alpha, Interleukin-6, Case-Control Studies, Transforming Growth Factor beta, Self-Injurious Behavior, Interleukin-10, Suicidal Ideation

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 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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