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3. SUICIDAL IDEATION IS ASSOCIATED WITH ELEVATED INFLAMMATION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER

Author

O'Donovan, Aoife, Rush, Gavin, Hoatam, Gerard, Hughes, Brian M, McCrohan, AnnMaria, Kelleher, Cecily, O'Farrelly, Cliona, and Malone, Kevin M

Subjects
Depression, Biological markers, Mood disorders, Stress, Suicide/self-harm
Abstract

BackgroundPatients 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.MethodsTo 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.ResultsPatients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η2 = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial η2 = .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 η2 = .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.ConclusionsSuicidal ideation may be uniquely associated with inflammation in depressed patients.

Published
2013

4. Clinical anxiety, cortisol and interleukin-6: Evidence for specificity in emotion-biology relationships

Author

O'Donovan, Aoife, Hughes, Brian M, Slavich, George M, Lynch, Lydia, Cronin, Marie-Therese, O’Farrelly, Cliona, and Malone, Kevin M

Subjects
Anxiety, Depression, Cortisol, Interleukin-6, Neuroticism
Abstract

Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases.

Published
2010

17. Neuroanatomic correlates of psychopathologic components of major depressive disorder

Author

Milak, Matthew S., Parsey, Ramin V., Keilp, John, Oquendo, Maria A., Malone, Kevin M., and Mann, J. John

Subjects
Neurotransmitters -- Research, Glucose metabolism -- Measurement, Depression, Mental -- Measurement, Depression, Mental -- Research, PET imaging, Brain research, Health, Psychology and mental health
Published
2005

19. Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression

Author

Oquendo, Maria A., Placidi, Giovanni P.A., Malone, Kevin M., Campbell, Carl, Keilp, John, Brodsky, Beth, Kegeles, Lawrence S., Cooper, Thomas B., Parsey, Ramin V., Heertum, Ronald L. van, and Mann, J. John

Subjects
Depression, Mental -- Physiological aspects, Suicidal behavior -- Physiological aspects, Serotonin metabolism, PET imaging, Health, Psychology and mental health
Published
2003

29. Anxiety in Major Depression

Author

PLACIDI, GIOVANNI P.A., OQUEDO, MARIA A., MALONE, KEVIN M., BRODSKY, BETH, ELLIS, STEVEN P., and MANN, J. JOHN

Published
2001

32. Delusions and Suicidality

Author

Grunebaum, Michael F., Oquendo, Maria A., Harkavy-Friedman, Jill M., Ellis, Steven P., Li, Shuhua, Haas, Gretchen L., Malone, Kevin M., and Mann, J. John

Published
2001

42. Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms

Author

Buckley Avril, Tewari Prerna, Bolger Sharon, Lynch Dermot, Casement Alison, Bannan Noreen, Maher Anne, Brown Katherine, Jeffers Anne, Reilly Michael, Brady John, O'Grady John, Corcoran Eleanor, McClelland Roy, Foster Tom, Kelly Chris, Ryan Maria, Murphy Therese M, Quinlivan Leah, Daly Leslie, Kelleher Cecily, and Malone Kevin M

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested. Methods DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions. Results Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse. Conclusion Preliminary findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.

Published
2011
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47. Dr. Mann and Colleagues Reply

Author

Mann, J. John, Malone, Kevin M., Diehl, David J., Perel, James, Cooper, Thomas B., and Mintun, Mark A.

Published
1997

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