A Preliminary Study of Cytokines in Suicidal and Nonsuicidal Adolescents with Major Depression
Open accessAbstract
BACKGROUND: Increased systemic cytokine levels, modulators of the immune system, have been repeatedly documented in adult and adolescent major depressive disorder (MDD). This preliminary study extends this work to test the role of cytokines in suicidal symptomatology in adolescent MDD. Hypotheses were that acutely suicidal depressed adolescents would have: (1) increased plasma levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, and (2) a proinflammatory/antiinflammatory cytokine imbalance (indexed by plasma IFN-gamma/IL-4), compared to nonsuicidal depressed adolescents and healthy controls. METHODS: Twelve suicidal adolescents with MDD (7 females [58%]; 5 medication-free/naïve), 18 nonsuicidal adolescents with MDD (12 females [67%]; 8 medication-free/naïve), and 15 controls (8 females [53%]) were enrolled. MDD had to be of at least 6 weeks duration, with a minimum severity score of 40 on the Children's Depression Rating Scale-Revised. Plasma cytokines were examined using enzyme-linked immunosorbent assays. Nonparametric tests were used to compare subject groups. RESULTS: Unexpectedly, suicidal adolescents with MDD had significantly decreased plasma TNF-alpha concentrations compared to nonsuicidal adolescents with MDD (1.33 +/- 2.95 pg/mL versus 30.9 +/- 110.9 pg/mL; p = 0.03). IFN-gamma was increased in both suicidal and nonsuicidal adolescents with MDD compared to controls (2.14 +/- 6.22 and 4.20 +/- 14.48 versus 0.37 +/- 0.64; p < 0.02, p = 0.005). Findings remained evident when controlled for age and gender. CONCLUSIONS: Our preliminary findings suggest that immune system dysregulation may be associated with suicidal symptomatology in adolescent MDD. These findings should be replicated in larger samples with medication-free adolescents.
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Adolescents with major depressive disorder and suicidal ideation showed higher interferon-γ levels than controls.
“adolescents with major depressive disorder and suicidal ideation (N = 12) showed higher levels of interferon-γ compared with controls (N = 15) (Gabbay et al. 2009)”
From Adolescent Suicide as a Failure of Acute Stress-Response Systems. (2019) · cites this paper as Gabbay et al. 2009
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“Clinical case reports worldwide have noted the emergence of depressive symptoms and death by suicide in patients treated with cytokines (Denicoff et al. 1987; Meyers 1999; Capuron et al. 2000; Capuron et al. 2001; Maes et al. 2001; Bonaccorso et al. 2002; Van Gool et al. 2003).”
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Attitudes to seclusion in Virginia
Mann, L. S., & Wise, T. N. (1989) · The British Journal of Psychiatry · doi:10.1192/bjp.155.2.263b · Cited by 15 · see citing works
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- Fujigaki S Saito K Sekikawa K Tone S Takikawa O Fujii H Wada H Noma A Seishima M Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism. Eur J Immunol 2001 31 2313 2318 11477543
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Understanding the Complex of Suicide in Depression: from Research to Clinics
Orsolini, L., Latini, R., Pompili, M., Serafini, G., Volpe, U., Vellante, F., Fornaro, M., Valchera, A., Tomasetti, C., Fraticelli, S., et al. (2020) · Psychiatry Investigation · doi:10.30773/pi.2019.0171 · Cited by 373 · see citing works
Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims
Pandey, G. N., Rizavi, H. S., Ren, X., Fareed, J., Hoppensteadt, D. A., Roberts, R. C., Conley, R. R., & Dwivedi, Y. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.08.006 · Cited by 378 · see citing works
“There is only one study of cytokines in the blood of adolescent suicidal patients by Gabbay et al. (2009). They found decreased plasma levels in adolescent suicidal patients with MDD, whereas IFN-γ was increased in both suicidal and non-suicidal MDD patients.”
BackgroundBlack, C., & Miller, B. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.10.014 · Cited by 366 · see citing works
Cytokine levels in the blood may distinguish suicide attempters from depressed patients
Janelidze, S., Mattei, D., Westrin, Å., Träskman-Bendz, L., & Brundin, L. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.10.010 · Cited by 298 · see citing works
Depression and inflammation among children and adolescents: A meta-analysis
Colasanto, M., Madigan, S. L., & Korczak, D. J. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.09.025 · Cited by 278 · see citing works
Role of Inflammation in Suicide: From Mechanisms to Treatment
Brundin, L., Bryleva, E. Y., & Thirtamara Rajamani, K. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.116 · Cited by 257 · see citing works
“However, there are studies that also report a decrease in cytokine levels in suicidal individuals (Clark et al , 2016; Gabbay et al , 2009).”
Loftis, J. M., Huckans, M. S., & Morasco, B. J. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.11.015 · Cited by 252 · see citing works
Inflammation 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
Adolescent Suicide as a Failure of Acute Stress-Response Systems.
Miller, A. B., & Prinstein, M. J. (2019) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050718-095625 · Cited by 235 · see citing works
“For instance, one study revealed that adolescents with major depressive disorder and suicidal ideation (N = 12) showed higher levels of interferon-γ compared with controls (N = 15) (Gabbay et al. 2009).”
BackgroundThe role of cytokines in the pathophysiology of suicidal behavior
Ganança, L., Oquendo, M. A., Tyrka, A. R., Cisneros-Trujillo, S., Mann, J. J., & Sublette, M. E. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.10.008 · Cited by 217 · see citing works
“, 2013), there was no difference in blood levels between depressed attempters and nonattempters, but cytokine levels did distinguish depressed patients from healthy controls (Gabbay et al., 2009; Kim et al., 2008; Lee and Kim, 2010), indicating more of a role as biomarkers for depression than suicide.”
BackgroundResultInfluentialSerafini, G., Parisi, V. M., Aguglia, A., Amerio, A., Sampogna, G., Fiorillo, A., Pompili, M., & Amore, M. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17072393 · Cited by 172 · see citing works
“(2009) [30] 12 suicidal adolescents, 18 non-suicidal adolescents with MDD, 15 controls Cross-sectional case-control study IFN-γ, TNF-α, IL-6, IL-1β, IL-4 Suicidal adolescents with MDD had significantly decreased plasma TNF-α concentrations compared to non-suicidal adolescents with MDD.”
BackgroundMethodInfluentialThe role of inflammatory cytokines in suicidal behavior: A systematic review
Serafini, G., Pompili, M., Elena Seretti, M., Stefani, H., Palermo, M., Coryell, W., & Girardi, P. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.06.002 · Cited by 151 · see citing works
“…in MDD suicidal behavior (Isung et al., 2012a, 2012b; Kim et al., 2008; Sublette et al., 2011; GrassiOliveira et al., 2012; Janelidze et al., 2011; Gabbay et al., 2009; Lindqvist et al., 2009; Mendlovic et al., 1999; Nassberger and Traskman-Bendz, 1993; Pandey et al., 2012; Boehm et al., 2010;…”
BackgroundMethodResultInfluentialNeuroinflammation in suicide: Toward a comprehensive model
Courtet, P., Giner, L., Seneque, M., Guillaume, S., Olie, E., & Ducasse, D. (2016) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2015.1054879 · Cited by 146 · see citing works
Comorbidity between depression and asthma via immune-inflammatory pathways: a meta-analysis
Jiang, M., Qin, P., & Yang, X. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.04.027 · Cited by 146 · see citing works
Lund-Sørensen, H., Benros, M. E., Madsen, T., Sørensen, H. J., Eaton, W. W., Postolache, T. T., Nordentoft, M., & Erlangsen, A. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.1594 · Cited by 131 · see citing works
A meta-analysis of cytokines in suicidal behavior
Ducasse, D., Olié, E., Guillaume, S., Artéro, S., & Courtet, P. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.02.004 · Cited by 119 · see citing works
The role of the kynurenine pathway in suicidality in adolescent major depressive disorder
Bradley, K. A. L., Case, J. A. C., Khan, O., Ricart, T., Hanna, A., Alonso, C. M., & Gabbay, V. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.03.031 · Cited by 115 · see citing works
“cytokine levels in suicidal depressed adolescents (Gabbay et al., 2009) and b) the KP”
Self-citationVasupanrajit, A., Jirakran, K., Tunvirachaisakul, C., Solmi, M., & Maes, M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01407-4 · Cited by 109 · see citing works
“As a result, future research should concentrate on the missing biomarkers, such as Treg cytokines like IL-10 and TGF-β1, as well as Th-2 cytokines like IL-4, IL-5, and IL-13 (see also ESF1 Table 1; column “what is missing in SB research”).”
BackgroundInfluentialA neuroimmunological perspective on anxiety disorders
Hou, R. H., & Baldwin, D. S. (2011) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1259 · Cited by 107 · see citing works
“In addition, the immune dysregulation hypothesis of major depression, which considers an altered balance of Th1 proinflammatory cytokines and Th2 anti-inflammatory cytokines with Th1 pathway being predominant over Th2 pathway, has also been proposed (Brietzke et al., 2009; Gabbay et al., 2009; Leonard and Myint, 2009).”
BackgroundInflammation and depression in young people: a systematic review and proposed inflammatory pathways
Toenders, Y. J., Laskaris, L., Davey, C. G., Berk, M., Milaneschi, Y., Lamers, F., Penninx, B. W. J. H., & Schmaal, L. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01306-8 · Cited by 98 · see citing works
Low plasma vascular endothelial growth factor (VEGF) associated with completed suicide
Isung, J., Mobarrez, F., Nordström, P., Åsberg, M., & Jokinen, J. (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.624549 · Cited by 94 · see citing works
“A dysregulation of the hypothalamic-pituitary-adrenal system (HPAS) and increased concentrations of proinfl ammatory cytokines have been described in major depressive disorder (MDD) and in suicide-related behaviour (Jokinen et al. 2007; Kim et al. 2008; Gabbay et al. 2009; Lindqvist et al. 2009; Janelidze et al. 2010).”
BackgroundSex Differences in the Peripheral Immune System in Patients with Depression
Birur, B., Amrock, E. M., Shelton, R. C., & Li, L. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00108 · Cited by 95 · see citing works
“Very few studies have examined inflammatory changes associated with suicidal behavior (21).”
BackgroundResearch Review: The role of cytokines in depression in adolescents: a systematic review
Mills, N. T., Scott, J. G., Wray, N. R., Cohen‐Woods, S., & Baune, B. T. (2013) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12080 · Cited by 91 · see citing works
Is depression the missing link between inflammatory mediators and cancer?
Polityńska, B., Pokorska, O., Wojtukiewicz, A. M., Sawicka, M., Mysliwiec, M., Honn, K. V., Tucker, S. C., & Wojtukiewicz, M. Z. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108293 · Cited by 80 · see citing works
Pallavi, P., Sagar, R., Mehta, M., Sharma, S., Subramanian, A., Shamshi, F., Sengupta, U., Qadri, R., Pandey, R. M., & Mukhopadhyay, A. K. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.04.033 · Cited by 77 · see citing works
“However similar studies in depressed adolescent population are very few (Gabbay et al., 2009; Högberg et al., 2012; Mamalakis et al., 2006).”
BackgroundÖzyurt, G., & Binici, N. C. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.08.007 · Cited by 74 · see citing works
Interleukin-1 β-Targeted Treatment Strategies in Inflammatory Depression: Toward Personalized Care
Ellul, P., Boyer, L., Groc, L., Leboyer, M., & Fond, G. (2016) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12656 · Cited by 65 · see citing works
“No association between suicide risk and neither IL-1b levels in the blood (two studies, N = 72 subjects) (70, 71) nor in the CSF (two studies, N = 37 subjects) (48, 49) has been found to date.”
BackgroundSerum cytokines and anxiety in adolescent depression patients: Gender effect
Pallavi, P., Sagar, R., Mehta, M., Sharma, S., Subramanian, A., Shamshi, F., Sengupta, U., Pandey, R. M., & Mukhopadhyay, A. K. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.06.036 · Cited by 69 · see citing works
“Immune system dysfunction in depression has been observed across different age groups (Penninx et al., 2003; Danese et al., 2008; Viscogliosi et al., 2011) including adolescents (Brambilla et al., 2004; Gabbay et al., 2009a, 2009b; Miller and Cole 2012; Henje Blom et al., 2012; Mcdade et al., 2013).”
BackgroundD’Acunto, G., Nageye, F., Zhang, J., Masi, G., & Cortese, S. (2019) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2019.0015 · Cited by 71 · see citing works
“Two studies (Gabbay et al. 2009a; Gariup et al. 2015) found significantly higher cytokine levels in youth with MDD compared with controls (IFN-c and IFN-c /IL-4 ratio 9 plus a trend for IL-6; IL-6, IL-8, and IL-1 b , respectively).”
InfluentialBerk, M., Mohebbi, M., Dean, O. M., Cotton, S., Chanen, A. M., Dodd, S., Ratheesh, A., Amminger, G. P., Phelan, M., Weller, A., et al. (2020) · BMC Medicine · doi:10.1186/s12916-019-1475-6 · Cited by 72 · see citing works
“Depression is associated with a complex picture of increased immune activation, impaired immune function, and inflammation [14–16], including in young people [17].”
BackgroundVasupanrajit, A., Jirakran, K., Tunvirachaisakul, C., & Maes, M. H. J. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.08.015 · Cited by 69 · see citing works
Henje, E., Lekander, M., Ingvar, M., Åsberg, M., Mobarrez, F., & Serlachius, E. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.10.002 · Cited by 68 · see citing works
The possible role of the kynurenine pathway in anhedonia in adolescents
Gabbay, V., Ely, B. A., Babb, J. S., & Liebes, L. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0685-7 · Cited by 66 · see citing works
Self-citationCampos, A. C., Vaz, G. N., Saito, V. M., & Teixeira, A. L. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.06.039 · Cited by 64 · see citing works
Li, Z., Qi, D., Chen, J., Zhang, C., Yi, Z., Yuan, C., Wang, Z., Hong, W., Yu, S., Cui, D., et al. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.05.005 · Cited by 63 · see citing works
Pérez‐Sánchez, G., Becerril‐Villanueva, E., Arreola, R., Martínez-Levy, G. A., Hernández, M. E., Velasco-Velázquez, M. A., Álvarez-Herrera, S., Cruz-Fuentes, C. S., Palacios, L., de la Peña, F., et al. (2018) · Mediators of Inflammation · doi:10.1155/2018/4074051 · Cited by 62 · see citing works
“Adolescents with MDD and suicidal tendencies have been reported to have significantly lower levels of TNF-α, as compared to those without suicidal tendencies and healthy volunteers [21].”
BackgroundResultInfluentialMultimodal Investigations of Reward Circuitry and Anhedonia in Adolescent Depression
Ely, B. A., Nguyen, T. N. B., Tobe, R. H., Walker, A., & Gabbay, V. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.678709 · Cited by 56 · see citing works
“We documented significantly higher levels of interferon-gamma (IFN-γ) in medically healthy adolescents with major depressive disorder compared to healthy controls (230, 231); unexpectedly, however, we found that suicidal depressed adolescents had decreased levels of tumor necrosis factor-alpha (TNF-α) compared to non-…”
Self-citationNovel investigational drugs targeting IL-6 signaling for the treatment of depression
Fonseka, T. M., McIntyre, R. S., Soczynska, J. K., & Kennedy, S. H. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.998334 · Cited by 53 · see citing works
“[81] MDD + high SI (n = 29), MDD + low SI (n = 45), nondepressed HC (n = 48) Higher IL-6 in MDD + high SI versus MDD + low SI or HC [74,82] [185,186]”
MethodAggression, impulsivity and inflammatory markers as risk factors for suicidal behavior
Coryell, W. H., Wilcox, H. C., Evans, S. J., Pandey, G. N., Jones‐Brando, L. V., Dickerson, F., & Yolken, R. H. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.09.004 · Cited by 53 · see citing works
Gabbay, V., Freed, R. D., Alonso, C. M., Senger, S., Stadterman, J., Davison, B. A., & KLEIN, R. G. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.17m11596 · Cited by 53 · see citing works
Self-citationThe role of the kynurenine pathway and quinolinic acid in adolescent major depressive disorder
Öztürk, M., Sapmaz, Ş. Y., Kandemir, H., Taneli, F., & Aydemir, Ö. (2020) · International journal of clinical practice · doi:10.1111/ijcp.13739 · Cited by 46 · see citing works
Relationships between inflammatory markers and suicide risk status in major depression
Ganança, L., Galfalvy, H., Cisneros-Trujillo, S., Basseda, Z., Cooper, T. B., Ren, X., Figueira, M. L., Oquendo, M. A., Mann, J. J., & Sublette, M. E. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.12.029 · Cited by 46 · see citing works
Anhedonia as a clinical correlate of inflammation in adolescents across psychiatric conditions
Freed, R. D., Mehra, L. M., Laor, D., Patel, M., Alonso, C. M., Kim‐Schulze, S., & Gabbay, V. (2018) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2018.1482000 · Cited by 42 · see citing works
Self-citationInflammatory markers and suicidal attempts in depressed patients: A review
Marini, S., Vellante, F., Matarazzo, I., Berardis, D. D., Serroni, N., Gianfelice, D., Olivieri, L., Renzo, F. D., Marco, A. D., Fornaro, M., et al. (2016) · International Journal of Immunopathology and Pharmacology · doi:10.1177/0394632015623793 · Cited by 42 · see citing works
Peters, A. T., Ren, X., Bessette, K. L., Goldstein, B. I., West, A. E., Langenecker, S. A., & Pandey, G. N. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.03.030 · Cited by 41 · see citing works
Dysfunctional adaptive immune response in adolescents and young adults with suicide behavior
Jha, M. K., Cai, L., Minhajuddin, A., Fatt, C. C., Furman, J. L., Gadad, B. S., Mason, B. L., Greer, T. L., Hughes, J. L., Xiao, G., et al. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104487 · Cited by 39 · see citing works
Wang, L., Wu, M.-S., Hsu, H.-J., Wu, I., Sun, C., Chou, C., Lee, C., Tsai, C., Tsai, Y.-C., & Chen, C. (2012) · The International Journal of Psychiatry in Medicine · doi:10.2190/pm.44.2.b · Cited by 41 · see citing works
“Some investigators have suggested that patients that attempt suicide had increased levels of IL-6 [20, 21] and decreased levels of IL-2 [19]; however, the correlation of TNF- and suicide has been inconsistent in previous studies [21, 46].”
BackgroundResultInflammatory markers and suicidal behavior: A comprehensive review of emerging evidence
Baldini, V., Gnazzo, M., Varallo, G., Atti, A. R., Ronchi, D. D., Fiorillo, A., & Plazzi, G. (2025) · Annals of General Psychiatry · doi:10.1186/s12991-025-00575-9 · Cited by 38 · see citing works
Increased ventricular cerebrospinal fluid lactate in depressed adolescents
Bradley, K., Mao, X., Case, J. A. C., Kang, G., Shungu, D. C., & Gabbay, V. (2016) · European Psychiatry · doi:10.1016/j.eurpsy.2015.08.009 · Cited by 38 · see citing works
“Work in our lab has documented immune system dysregulation and increased levels of proinflammatory cytokines – proteins that function as signaling molecules to modulate immune responses – in adolescent MDD [15,16].”
BackgroundSelf-citationEidan, A. J., AL-Harmoosh, R. A., & Al-Amarei, H. M. (2019) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2018.0134 · Cited by 37 · see citing works
Bradley, K., Stern, E. R., Alonso, C. M., Xie, H., Kim‐Schulze, S., & Gabbay, V. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.014 · Cited by 38 · see citing works
Self-citationAmitai, M., Taler, M., Baruch, R. B., Lebow, M., Rotkopf, R., Apter, A. S., Fennig, S., Weizman, A., & Chen, A. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.12.017 · Cited by 39 · see citing works
“…effects of ADs on circulatory cytokine levels were documented in adults (Lanquillon et al., 2000; Yoshimura et al., 2013; Hannestad et al., 2011; Gabbay et al., 2009), with few publications in pediatric populations (Pandey et al., 2012; Amitai et al., 2016; Zohar et al., 2018; PérezSánchez et…”
BackgroundInfluentialLee, H., Song, M., Lee, J., Kim, J.-B., & Lee, M. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.01.125 · Cited by 35 · see citing works
Psychological and neurobiological aspects of suicide in adolescents: Current outlooks
Vargas‐Medrano, J., Diaz-Pacheco, V., Castaneda, C. A., Miranda-Arango, M., Longhurst, M. O., Martin, S. L., Ghumman, U., Mangadu, T., Chheda, S., Thompson, P. M., et al. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100124 · Cited by 35 · see citing works
Correlates of suicidality in young people with depressive disorders: A systematic review
Moller, C. I., Davey, C. G., Badcock, P. B., Wrobel, A. L., Cao, A., Murrihy, S., Sharmin, S., & Cotton, S. (2022) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/00048674221086498 · Cited by 35 · see citing works
“Severity was assessed through a variety of standardised scales, the most common being the Beck Scale for Suicidal Ideation (BSS) (Beck et al., 1979) which was used in four studies (Fan et al., 2019; Gabbay et al., 2009; Johnston et al., 2017; Seo et al., 2015).”
BackgroundMethodResultInfluentialCostanza, A., Amerio, A., Aguglia, A., Serafini, G., Amore, M., Hasler, R., Ambrosetti, J., Bondolfi, G., Sampogna, G., Berardelli, I., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104606 · Cited by 35 · see citing works
Latent infection, inflammatory markers and suicide attempt history in depressive disorders
Coryell, W. H., Wilcox, H. C., Evans, S. J., Pandey, G. N., Jones‐Brando, L. V., Dickerson, F., & Yolken, R. H. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.057 · Cited by 33 · see citing works
Fernández-Sevillano, J., González–Ortega, I., MacDowell, K. S., Zorrilla, E. P., López, M. P., Courtet, P., Gabilondo, A., Martínez‐Cengotitabengoa, M., Leza, J. C., Sáiz, P. A., et al. (2021) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2021.1988703 · Cited by 34 · see citing works
“Some findings in literature do not support the relationship between suicide and IL-6 (Kim et al. 2008; Gabbay et al. 2009; Isung et al. 2012; Su et al. 2020; Ganança et al. 2021), IL-2 (Mendlovic et al. 1999), IL-4 (Mendlovic et al. 1999; Gabbay et al. 2009; Isung et al. 2012) and TNF-a (Lindqvist…”
ResultInfluentialSpíndola, L., Pan, P. M., Moretti, P. N. S., Ota, V., Santoro, M. L., Cogo‐Moreira, H., Gadelha, A., Salum, G. A., Manfro, G. G., Mari, J. D. J., et al. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.03.015 · Cited by 31 · see citing works
A probe in the connection between inflammation, cognition and suicide
Cáceda, R., Griffin, W. S. T., & Delgado, P. L. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881118764022 · Cited by 30 · see citing works
Song, L., Quan, X., Su, L., Wang, K., Wang, H., Wu, L., Chen, C., Li, S., Xiang, W., Chen, L., et al. (2020) · Brain and Behavior · doi:10.1002/brb3.1771 · Cited by 26 · see citing works
“Tsao et al. have reported that elevated levels of IFN-γ may be associated with major depressive disorder (MDD) and that the enzyme “indoleamine 2,3-dioxygenase (IDO)” plays a role in a depression-related signaling cascade (Gabbay et al., 2009; Simon et al., 2008; Tsao, Lin, Chen, Bai, & Wu, 2006).”
BackgroundChanges In Plasma NPY, IL-1β And Hypocretin In People Who Died By Suicide
Lü, J., Li, S., Li, H., Mou, T., Zhou, L., Huang, B., Huang, M., & Xu, Y. (2019) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s219962 · Cited by 25 · see citing works
“However, Gabbay et al claimed that plasma IL-1β levels among suicidal teenagers with MDD, suicidal adolescents with MDD, nonsuicidal adolescents with MDD and healthy controls showed no difference.(36) In addition, studies reported that psychiatric patients with suicide attempts and controls were found to have no signi…”
ResultHansen, H. G., Köhler‐Forsberg, O., Petersen, L. V., Nordentoft, M., Postolache, T. T., Erlangsen, A., & Benros, M. E. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.11.008 · Cited by 26 · see citing works
Inflammation and internalizing disorders in adolescents
da Silva, C. T. B., Costa, M. D. A., Kapczinski, F. P., de Aguiar, B. W., Salum, G. A., & Manfro, G. G. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.03.023 · Cited by 24 · see citing works
Sun, X., Liu, Y., Dai, T., Ding, J. H., & Hu, G. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.05.047 · Cited by 24 · see citing works
Inflammation, depressive symptoms, and emotion perception in adolescence
Peters, A. T., Ren, X., Bessette, K. L., George, N., Kling, L. R., Thies, B., West, A. E., Langenecker, S. A., & Pandey, G. N. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.08.126 · Cited by 22 · see citing works
González-Castro, T. B., Tovilla-Zárate, C. A., López-Narváez, M. L., Genis-Mendoza, A. D., & Juárez-Rojop, I. E. (2021) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2020.0265 · Cited by 21 · see citing works
Yang, S., Han, J., Ye, Z., Zhou, H., Yan, Y., Han, D., Chen, S., Wang, L., Feng, Q., Zhao, X., et al. (2024) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-024-02579-4 · Cited by 19 · see citing works
“Numerous studies have suggested that inflammatory activation was not only associated with more severe symptoms and treatment resistance in depressed patients, but also as one of the important biological changes in depressed patients with suicidal ideation or behavior [33, 35, 54].”
Quinn, A. L., Dean, O. M., Davey, C. G., Kerr, M., Harrigan, S., Cotton, S., Chanen, A. M., Dodd, S., Ratheesh, A., Amminger, G. P., et al. (2015) · Early Intervention in Psychiatry · doi:10.1111/eip.12280 · Cited by 20 · see citing works
“Adolescent depression is associated with an inflammatory response.(13) Elevated levels of C-reactive protein (CRP; a marker of inflammation) predict the later onset of depression, suggesting that the immune findings contribute to the genesis of the disorder.”
BackgroundGuo, Y., Jiang, X., Jia, L., Zhu, Y., Han, X., Wu, Y., Liu, W., Zhao, W., Zhu, H., Wang, D., et al. (2022) · NeuroImage Clinical · doi:10.1016/j.nicl.2023.103403 · Cited by 18 · see citing works
“However, Gabbay et al. found no significant difference in plasma IL-6 level in adolescent MDD + S compared with adolescent MDD − S (Gabbay et al., 2009).”
BackgroundResultGuo, J., Zhang, T., Chen, W., Tan, J., Li, X., Zheng, A., Fu, Y., & Qiu, T. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05724-0 · Cited by 18 · see citing works
“However, most case-control studies reported no significant difference in peripheral IL-1βbetween adolescents with depression and healthy controls [38–40], which is consistent with our research.”
ResultPro-inflammatory Cytokines in Psychiatric Disorders in Children and Adolescents: A Review
Miłkowska, P., Popko, K., Demkow, U. A., & Wolańczyk, T. (2017) · Advances in experimental medicine and biology · doi:10.1007/5584_2017_32 · Cited by 18 · see citing works
Donegan, J. J., & Nemeroff, C. B. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-19-7376-5_17 · Cited by 18 · see citing works
Knowles, E. E. M., Curran, J. E., Göring, H. H. H., Mathias, S. R., Mollon, J., Rodrigue, A., Olvera, R. L., Leandro, A. C., Duggirala, R., Almasy, L. A., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.004 · Cited by 17 · see citing works
Lang, X., Trihn, T. H., Wu, H. E., Tong, Y., Xiu, M., & Zhang, X. (2020) · Aging · doi:10.18632/aging.102692 · Cited by 15 · see citing works
Qiao, D., Qi, Y., Zhang, X., Wen, Y., Huang, Y., Li, Y., Liu, P., Li, G., & Liu, Z. (2025) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-025-02709-6 · Cited by 15 · see citing works
“Inflammation has emerged as one pathophysiologic pathway contributing to NSSI [6–8].”
Polymorphism in CRHR1 gene affects the IL-1β levels in suicidal attempters
Bastos, C. R., Gazal, M., Quevedo, L. D. Á., Costa, J. L., Wiener, C. D., Jansen, K., de Mola, C. L., Oses, J. P., Souza, L. D. D. M., Portela, L. V., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.11.009 · Cited by 15 · see citing works
Lopizzo, N., Mazzelli, M., Zonca, V., Begni, V., D’Aprile, I., Cattane, N., Pariante, C. M., Riva, M. A., & Cattaneo, A. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104794 · Cited by 15 · see citing works
Hiking in Suicidal Patients: Neutral Effects on Markers of Suicidality
Neunhäeuserer, D., Sturm, J., Baumgartlinger, M. M., Niederseer, D., Ledl-Kurkowski, E., Steidle‐Kloc, E., Plöderl, M., Fartacek, C., Kralovec, K., Fartacek, R. R., et al. (2013) · The American Journal of Medicine · doi:10.1016/j.amjmed.2013.05.008 · Cited by 14 · see citing works
Molecular Biomarkers for Pediatric Depressive Disorders: A Narrative Review
Lee, J., Chi, S., & Lee, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221810051 · Cited by 12 · see citing works
“Consequently, further research on TNF-α is required [29].”
BackgroundMethodInfluentialReal, A. G., Fontanari, A. M. V., Costa, Â. B., Soll, B. M. B., Bristot, G., de Oliveira, L. F., Kamphorst, A. M., Schneider, M. A., & Lobato, M. I. R. (2021) · Trends in Psychiatry and Psychotherapy · doi:10.47626/2237-6089-2020-0007 · Cited by 13 · see citing works
Tsujimura, A., Miyagawa, Y., Okuda, H., Yamamoto, K., Fukuhara, S., Nakayama, J., Takao, T., Nonomura, N., & Okuyama, Ä. (2010) · The Aging Male · doi:10.3109/13685538.2010.502268 · Cited by 13 · see citing works
Yang, Y., Gu, K., & Li, J. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1422511 · Cited by 12 · see citing works
Pro-Inflammatory Cytokines in Psychiatric Disorders in Children and Adolescents: A Review
Miłkowska, P., Popko, K., Demkow, U. A., & Wolańczyk, T. (2017) · Advances in experimental medicine and biology · doi:10.1007/5584_2017_24 · Cited by 12 · see citing works
Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents
Liu, Q., Ely, B. A., Simkovic, S. J., Alonso, C. M., & Gabbay, V. (2021) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2020.0201 · Cited by 12 · see citing works
“Work by our group and others has shown increased levels of immune mediators in both adults and children with depression as well as other psychiatric disorders (Gabbay et al. 2009a, 2009b, 2009c, 2010; Miller et al. 2009; Bradley et al. 2015, 2019; Freed et al. 2019).”
Self-citationHowe, A. S., & Lynch, D. A. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100490 · Cited by 12 · see citing works
Peripheral Markers of Suicidal Behavior: Current Findings and Clinical Implications
Kang, H.-J., Kim, J.-W., Kim, S.-W., Han, J.-S., Lyoo, I., & Kim, J.-M. (2023) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.22.1046 · Cited by 9 · see citing works
“In our review, only one study found an association between low plasma IL-4 [18] and SR, whereas three studies found no association between peripheral IL-4 level and SR [16, 17,30].”
InfluentialProinflammatory cytokine levels in patients with conversion disorder
Tiyekli, U., Çalıyurt, O., & Tiyekli, N. D. (2012) · Acta Neuropsychiatrica · doi:10.1111/j.1601-5215.2012.00676.x · Cited by 10 · see citing works
“(55), studied adolescents with major depression but unexpectedly found that suicidal adolescents had significantly decreased TNF-α levels compared to non-suicidal ones with major depression.”
BackgroundAre sick people really more impulsive?: Investigating inflammation-driven impulsivity
Madison, A. A., & Kiecolt‐Glaser, J. K. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.105763 · Cited by 10 · see citing works
González‐Castro, T. B., Tovilla‐Zárate, C. A., Juárez‐Rojop, I. E., López‐Narváez, M. L., Pérez‐Hernández, N., Rodrı́guez-Pérez, J. M., & Mendoza, A. D. G. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.10.024 · Cited by 12 · see citing works
Ayodele, A., Adetunla, A., & Akinlabi, E. T. (2024) · International Journal of Online and Biomedical Engineering (iJOE) · doi:10.3991/ijoe.v20i09.47581 · Cited by 9 · see citing works
RetractedGenetic variations related to inflammation in suicidal ideation and behavior: A systematic review
Tamimou, R., Lumbroso, S., Mouzat, K., & López‐Castromán, J. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1003034 · Cited by 9 · see citing works
“Plasma interleukin 4 (IL-4) levels were similar in suicide ideators compared to a control group (17) and suicide completers (SCs) compared to other SAs that did not die by suicide (15).”
ResultLinkas, J., Ahmed, L. A., Csifcsák, G., Emaus, N., Furberg, A., Grimnes, G., Pettersen, G., Rognmo, K., & Christoffersen, T. (2022) · BMC Psychology · doi:10.1186/s40359-022-00779-8 · Cited by 9 · see citing works
Biological Indicators of Suicide Risk in Youth With Mood Disorders: What Do We Know So Far?
Lewitzka, U., Doucette, S., Seemüller, F., Grof, P., & Duffy, A. C. (2012) · Current Psychiatry Reports · doi:10.1007/s11920-012-0329-0 · Cited by 8 · see citing works
Peripheral and neural correlates of self-harm in children and adolescents: a scoping review
Sparrow-Downes, V. M., Trincao-Batra, S., Cloutier, P., Helleman, A., Salamatmanesh, M., Gardner, W., Baksh, A., Kapur, R., Sheridan, N., Suntharalingam, S., et al. (2021) · BMC Psychiatry · doi:10.1186/s12888-022-03724-6 · Cited by 9 · see citing works
“Clark et al. 2003 US [81] Suicidality Cohort Precursor levels, prediction symptoms Crowell et al. 2005 US [51] Any self‑harm Case‑control Serotonin levels Crowell et al. 2008 US [82] Any self‑harm Case‑control Serotonin levels Dahl et al., 1990 US [83] Suicidality Case‑control Sleep characteristics Dahl et al. 1991b U…”
Vasupanrajit, A., Jirakran, K., Tunvirachaisakul, C., Solmi, M., & Maes, M. H. J. (2021) · Preprints.org · doi:10.20944/preprints202109.0159.v1 · Cited by 8 · see citing works
Clayton, M. G., Nelson, B. W., Giletta, M., Hastings, P. D., Nock, M. K., Rudolph, K. D., Slavich, G. M., & Prinstein, M. J. (2023) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-023-01033-4 · Cited by 7 · see citing works
“…levels of cytokine inflammation (Pandey et al., 2012 ; Serafini et al., 2020), other research on suicide revealed no associations with basal proinflammatory markers (Jha et al., 2020 ) or even lower levels of TNF-α in suicidal adolescents when compared to nonsuicidal controls (Gabbay et al., 2009).”
ResultPotential Neuroimmunological Targets in the Treatment of Anxiety Disorders
Hou, R. H., Tang, Z., & Baldwin, D. S. (2013) · Modern trends in psychiatry · doi:10.1159/000351965 · Cited by 7 · see citing works
Nguyen, T. N. B., Ely, B. A., Pick, D., Patel, M., Xie, H., Kim‐Schulze, S., & Gabbay, V. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.07.163 · Cited by 7 · see citing works
Self-citationThe Relationship between Serum Endocan Levels and Depression in Alzheimer’s Disease
Yoon, K. H., Kim, S. Y., Moon, Y. S., Roh, D. D., Lee, S., & Kim, D. H. (2016) · Disease Markers · doi:10.1155/2016/8254675 · Cited by 7 · see citing works
- Authors
- Gabbay, V., Klein, R. G., Guttman, L. E., Babb, J. S., Alonso, C. M., Nishawala, M., Katz, Y., Gaite, M. R., & Gonzalez, C. J.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- New York University (US)
- Harvard University (US)
- New York State Department of Health (US)
- Corresponding author
- Gabbay, Vilma
- Venue
- Journal of Child and Adolescent Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2009-08
- Volume
- 19
- Issue
- 4
- Pages
- 423-430
- ISSN
- 1044-5463 (ISSN-L)
- 1557-8992
- PMC
- PMC2778037
- OpenAlex
- W1993942689
- Cited by
- 136
- References
- 53
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 9 · 2023: 4 · 2022: 16 · 2021: 16 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 8 · 2016: 7 · 2015: 11 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Child and Adolescent Psychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH077072, K23MH077072)
- National Center for Research Resources (M01 RR 00096, M01RR000096)
- National Center for Complementary and Integrative Health (R21AT002395, AT002395)
- 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, adolescent major depressive disorder, cytokines, TNF-α, interferon-gamma, interleukin-6, IL-1β, IL-4, immune dysregulation, plasma cytokines
- MeSH terms
- Adolescent, Age Factors, Child, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Suicide, Tumor Necrosis Factor-alpha, Cytokines, Young Adult
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