The DOI matches its Crossref record; 121 of the 121 references it cites were found in a registry or an index.
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Open accessAbstract
Recognition that inflammation may represent a common mechanism of disease has been extended to include neuropsychiatric disorders including major depression. Patients with major depression have been found to exhibit increased peripheral blood inflammatory biomarkers, including inflammatory cytokines, which have been shown to access the brain and interact with virtually every pathophysiologic domain known to be involved in depression, including neurotransmitter metabolism, neuroendocrine function, and neural plasticity. Indeed, activation of inflammatory pathways within the brain is believed to contribute to a confluence of decreased neurotrophic support and altered glutamate release/reuptake, as well as oxidative stress, leading to excitotoxicity and loss of glial elements, consistent with neuropathologic findings that characterize depressive disorders. Further instantiating the link between inflammation and depression are data demonstrating that psychosocial stress, a well-known precipitant of mood disorders, is capable of stimulating inflammatory signaling molecules, including nuclear factor kappa B, in part, through activation of sympathetic nervous system outflow pathways. Interestingly, depressed patients with increased inflammatory biomarkers have been found to be more likely to exhibit treatment resistance, and in several studies, antidepressant therapy has been associated with decreased inflammatory responses. Finally, preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication. Translational implications of these findings include the unique opportunity to identify relevant patient populations, apply immune-targeted therapies, and monitor therapeutic efficacy at the level of the immune system in addition to behavior.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Patients with major depressive disorder exhibit all of the cardinal features of an inflammatory response, including increased expression of pro-inflammatory cytokines and their receptors and increased levels of acute-phase reactants, chemokines and soluble adhesion molecules in peripheral blood and cerebrospinal fluid (CSF)16,17.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, prolonged inflammatory signaling, such as when the inflammatory response is maintained by ongoing psychosocial stress, can have detrimental effects that include risk for depression and other psychiatric diseases (Dantzer et al., 2008; Miller et al., 2009; Miller and Raison, 2016; Slavich and Irwin, 2014).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Miller et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“we found, like others,14 that SSRI might have a beneficial effect on inflammation”
From Association of depressive disorders, depression characteristics and antidepressant medication with inflammation (2012) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Earlier studies found decreases in inflammatory marker levels after antidepressant treatment, mainly SSRI (see ref. 14 for an overview)”
From Association of depressive disorders, depression characteristics and antidepressant medication with inflammation (2012) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Meta-analyses of the literature conclude that peripheral blood IL-1β, IL-6, TNF and C-reactive protein (CRP) are the most reliable biomarkers of inflammation in patients with depression16.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [16]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“increased expression of a variety of innate immune genes and proteins, including IL-1β, IL-6, TNF, Toll-like receptor 3 (TLR3) and TLR4, has been found in post-mortem brain samples from suicide victims that had depression16,18,19,21.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“is sufficient to induce depressive-like behavior in rodent models”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“is activated in conditions associated with depression in humans and in rodent models”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As a consequence of these lingering effects, childhood adversity may predispose individuals to complicated depressions, characterized by treatment non-response, residual mood symptoms, or frequent relapse (3, 35).”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [3]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“the inflammatory cytokine interleukin-6 (IL-6) is elevated in the serum of a subset of depressed patients”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“a growing recognition that immune system actions profoundly impact mood regulation (3–6)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“The growing evidence of causative links between inflammation and depression (3, 4) indicates that targets of inflammatory molecules contribute to establishing a pro-depressant environment.”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Most center around the notion that stress triggers the release of pro-inflammatory cytokines, which access the central nervous system, eliciting neurobehavioral adjustments that manifest as depressive symptoms (3–5).”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [3]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“whereas deletion of the IL-6 gene is protective (3–5, 8)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [4]
Experimental — accuracy not yet measuredIn the citing paper
“Experimental data indicate that acute psychosocial stress (e.g., public speaking, mental arithmetic) stimulates inflammatory signaling molecules194, and these responses are exaggerated in patients with depression190.”
From Psychobiological factors of resilience and depression in late life (2019) · cites this paper as [190]
In the citing paper
“Both younger190 and older191 adults with depression show increased levels of inflammatory cytokines, secreted proteins that interact with virtually every depression-relevant neurophysiological domain (e.g., neurotransmitter metabolism, neuroendocrine function, and neural plasticity).”
From Psychobiological factors of resilience and depression in late life (2019) · cites this paper as [190]
In the citing paper
“A wealth of evidence has implicated inflammation in the development of depression.”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Miller et al., 2009
In the citing paper
“Cytokines also have the capability of influencing neurocircuitry and neurotransmitter systems to produce behavioral alterations (Miller et al., 2009, Haroon et al., 2012).”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Miller et al., 2009
In the citing paper
“Furthermore, administration of cytokines to humans and laboratory animals produces neuropsychiatric symptoms and behavioral alterations consistent with depression (Miller et al., 2009).”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Miller et al., 2009
In the citing paper
“Interestingly, all of these pathways have been demonstrated to be affected by inflammatory cytokines (Pace et al., 2007, Dantzer et al., 2008, Miller et al., 2009, Haroon et al., 2012) (Figure 1).”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Miller et al., 2009
In the citing paper
“In addition, IL-6 and IL-1β may contribute to the pathophysiology of a subset of patients with MDD via excessive release of corticotrophin releasing hormone (CRH) and by the promotion glucocorticoid receptor resistance, which may ultimately impair the negative feedback regulation of the HPA axis (59,60).”
From Peripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies (2017) · cites this paper as [59]
In the citing paper
“central nervous system (CNS) inflammation has been suggested to play a significant role in MDD pathogenesis due to findings of increased proinflammatory cytokines levels in patients with neurodegeneration and symptoms of depression such as anhedonia, depressed mood, and lethargy (Miller et al., 2009).”
From A Review of the Relationship between Proinflammatory Cytokines and Major Depressive Disorder (2014) · cites this paper as Miller et al., 2009
In the citing paper
“depressed patients with increased inflammatory biomarkers are more likely to be resistant to antidepressant therapy, a response to treatment has been associated with decreased inflammatory responses”
From Glucocorticoids, cytokines and brain abnormalities in depression (2011) · cites this paper as Miller et al., 2009
In the citing paper
“however, increasing preclinical and clinical evidence suggests that higher levels of oxidative stress, alterations in the Keap1-Nrf2 pathway, and Nrf2-associated inflammation are involved in the pathogenesis of these psychiatric disorders [128,129,130,131,132].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [129]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,188
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Mammalian MAP kinase signalling cascades
Chang, L., & Karin, M. (2001) · Nature · doi:10.1038/35065000 · Cited by 5,118
Depression, chronic diseases, and decrements in health: results from the World Health Surveys
Moussavi, S., Chatterji, S., Verdes, E., Tandon, A., Patel, V., & Ustun, B. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61415-9 · Cited by 4,070
Anterior Cingulate Cortex, Error Detection, and the Online Monitoring of Performance
Carter, C. S., Braver, T. S., Barch, D. M., Botvinick, M. M., Noll, D., & Cohen, J. D. (1998) · Science · doi:10.1126/science.280.5364.747 · Cited by 3,273
Antiinflammatory Action of Glucocorticoids — New Mechanisms for Old Drugs
Rhen, T., & Cidlowski, J. A. (2005) · New England Journal of Medicine · doi:10.1056/nejmra050541 · Cited by 3,149
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
Self-citationKern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e745 · Cited by 1,883
Astrocytes, from brain glue to communication elements: the revolution continues
Volterra, A., & Meldolesi, J. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1722 · Cited by 1,837
Cited by
Sorted by citations
Items 301–400 of 407
Cheng, Y., Jope, R. S., & Beurel, E. (2015) · BMC Neuroscience · doi:10.1186/s12868-015-0169-z · Cited by 70
Mean platelet volume in bipolar disorder:The search for an ideal biomarker
Mert, D. G., & Terzi, H. (2016) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s112374 · Cited by 67
Khandaker, G. M., Zammit, S., Lewis, G., & Jones, P. B. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.02.003 · Cited by 65
“…and other mood-relevant neurotransmitters, (ii) stimulation of the hypothalamic-pituitary-adrenal axis and release of corticotrophin releasing hormone in hypothalamus and amygdala, (iii) increasing oxidative stress and thus reducing synaptic plasticity (Dantzer et al., 2008; Miller et al., 2009).”
Depression subtypes in pediatric inflammatory bowel disease
Szigethy, E. M., Youk, A. O., Benhayon, D., Fairclough, D. L., Newara, M. C., Kirshner, M. A., Bujoreanu, S. I., Mrakotsky, C., Bousvaros, A., Srinath, A. I., et al. (2014) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000000262 · Cited by 65
Mast cells in chronic inflammation, pelvic pain and depression in women
Graziottin, A., Skaper, S. D., & Fusco, M. (2014) · Gynecological Endocrinology · doi:10.3109/09513590.2014.911280 · Cited by 63
Liang, G., Kow, A. S. F., Yusof, R., Tham, C. L., Ho, Y.-C., & Lee, M. T. (2024) · Biomedicines · doi:10.3390/biomedicines12010184 · Cited by 68
A gene expression atlas for different kinds of stress in the mouse brain
Flati, T., Gioiosa, S., Chillemi, G., Mele, A., Oliverio, A., Mannironi, C., Rinaldi, A., & Castrignanò, T. (2020) · Scientific Data · doi:10.1038/s41597-020-00772-z · Cited by 65
Silverman, M. N., Mukhopadhyay, P., Belyavskaya, E., Tonelli, L. H., Revenis, B. D., Doran, J. H., Ballard, B. E., Tam, J., Pacher, P., & Sternberg, E. M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.131 · Cited by 64
Liu, C., Carvalho, A., & McIntyre, R. (2015) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666141130204031 · Cited by 61
Shi, Z., Ren, H., Huang, Z., Peng, Y., He, B., Yao, X., Yuan, T.-F., & Su, H. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0212-9 · Cited by 62
Puterman, E., Epel, E. S., Lin, J., Blackburn, E. H., Gross, J. J., Whooley, M. A., & Cohen, B. E. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.05.008 · Cited by 61
Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans
Grigoleit, J.-S., Oberbeck, J. R., Lichte, P., Kobbe, P., Wolf, O. T., Montag, T., Rey, A. D., Gizewski, E. R., Engler, H., & Schedlowski, M. (2010) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2010.09.011 · Cited by 59
Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration
Neis, V. B., Manosso, L. M., Moretti, M., Freitas, A. E., Daufenbach, J., & Rodrigues, A. L. S. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.12.038 · Cited by 59
Glucocorticoids and Inflammation: A Double-Headed Sword in Depression?
Horowitz, M. A., Zunszain, P. A., Anacker, C., Musaelyan, K., & Pariante, C. M. (2013) · Modern Trends in Psychiatry · doi:10.1159/000343980 · Cited by 57
Tabatabaeizadeh, S.-A., Abdizadeh, M. F., Meshkat, Z., Khodashenas, E., Darroudi, S., Fazeli, M., Ferns, G. A., Avan, A., & Ghayour-Mobarhan, M. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.11.014 · Cited by 55
Braun, S. E., Kinser, P. A., & Rybarczyk, B. (2019) · Translational Behavioral Medicine · doi:10.1093/tbm/iby059 · Cited by 56
Cyclooxygenase-2 inhibition reduces stress-induced affective pathology
Gamble-George, J. C., Baldi, R., Halladay, L., Kocharian, A., Hartley, N., Silva, C. G., Roberts, H., Haymer, A., Marnett, L. J., Holmes, A., et al. (2016) · eLife · doi:10.7554/elife.14137 · Cited by 55
Transcriptomic predictors of inflammation-induced depressed mood
Cho, J. H.-J., Irwin, M. R., Eisenberger, N. I., Lamkin, D. M., & Cole, S. W. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0316-9 · Cited by 54
Huang, C., Yang, X., Zeng, B., Zeng, L., Gong, X., Zhou, C., Xia, J., Lian, B., Qin, Y., Yang, L., et al. (2019) · Journal of Proteomics · doi:10.1016/j.jprot.2018.11.023 · Cited by 54
He, M.-C., Shi, Z., Sha, N.-N., Chen, N., Peng, S.-Y., Liao, D.-F., Wong, M.-S., Dong, X.-L., Wang, Y.-J., Yuan, T.-F., et al. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.01.021 · Cited by 54
Inflammatory Biomarkers in Depression: An Opportunity for Novel Therapeutic Interventions
Li, M., Soczynska, J. K., & Kennedy, S. H. (2011) · Current Psychiatry Reports · doi:10.1007/s11920-011-0210-6 · Cited by 53
Effects of acute systemic inflammation on the interplay between sad mood and affective cognition.
Benson, S., Brinkhoff, A., Lueg, L., Roderigo, T., Kribben, A., Wilde, B., Witzke, O., Engler, H., Schedlowski, M., & Elsenbruch, S. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0043-0 · Cited by 53
Chen, D., Zhang, Y., Huang, T., & Jia, J. (2023) · Psychological Medicine · doi:10.1017/s0033291723000867 · Cited by 52
Chen, G.-Q., Peng, C.-L., Lian, Y., Wang, B.-W., Chen, P.-Y., & Wang, G.-P. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.662357 · Cited by 55
Bergmans, R. S., Kelly, K. M., & Mezuk, B. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.11.046 · Cited by 50
Inflamed brain: Targeting immune changes and inflammation for treatment of depression
Sakamoto, S., Zhu, X., Hasegawa, Y., Karma, S., Obayashi, M., Alway, E., & Kamiya, A. (2021) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13286 · Cited by 51
Han, K.-M., Tae, W.-S., Kim, A., Kang, Y., Kang, W., Kang, J., Kim, Y.-K., Kim, B., Seong, J. Y., & Ham, B.-J. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.03.021 · Cited by 50
The dose makes the poison: From glutamate-mediated neurogenesis to neuronal atrophy and depression
Rubio-Casillas, A., & Fernández-Guasti, A. (2016) · Reviews in the Neurosciences · doi:10.1515/revneuro-2015-0066 · Cited by 49
El-Marasy, S. A., El Awdan, S. A., Hassan, A., Ahmed-Farid, O. A., & Ogaly, H. A. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109329 · Cited by 50
Bot, M., Milaneschi, Y., Penninx, B. W. J. H., & Drent, M. L. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.02.028 · Cited by 50
Adaptation of Lipid Profiling in Depression Disease and Treatment: A Critical Review
Pinto, B., Conde, T., Domingues, I., & Domingues, M. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042032 · Cited by 51
Serum Interferon-Gamma Level Is Associated with Drug-Naïve Major Depressive Disorder
Daria, S., Proma, M. A., Shahriar, M., Islam, S. M. A., Bhuiyan, M. A., & Islam, M. R. (2020) · SAGE Open Medicine · doi:10.1177/2050312120974169 · Cited by 46
Hoyo-Becerra, C., Huebener, A., Trippler, M., Lutterbeck, M., Liu, Z. J., Truebner, K., Bajanowski, T., Gerken, G., Hermann, D. M., & Schlaak, J. F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083149 · Cited by 49
Mello, B. S. F., Chaves Filho, A. J. M., Custódio, C. S., Cordeiro, R. C., Miyajima, F., de Sousa, F. C. F., Vasconcelos, S. M. M., de Lucena, D. F., & Macedo, D. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.04.009 · Cited by 45
Hayley, S., Scharf, J., & Anisman, H. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.07.023 · Cited by 48
Cancer and post-traumatic stress disorder: Diagnosis, pathogenesis and treatment considerations
Rustad, J. K., David, D., & Currier, M. B. (2012) · Palliative and Supportive Care · doi:10.1017/s1478951511000897 · Cited by 48
Hadlandsmyth, K., Dailey, D. L., Rakel, B. A., Zimmerman, M. B., Vance, C. G., Merriwether, E. N., Chimenti, R. L., Geasland, K. M., Crofford, L. J., & Sluka, K. A. (2020) · Journal of Health Psychology · doi:10.1177/1359105317736577 · Cited by 48
Circulating T helper 17 and IFN-γ positive Th17 cells in Major Depressive Disorder
Ghosh, R., Kumar, P. K., Mitra, P., Purohit, P., Nebhinani, N., & Sharma, P. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112811 · Cited by 47
Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics
de Sousa, R. T., V. Zanetti, M., R. Brunoni, A., & Machado-Vieira, R. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150630173522 · Cited by 43
“A possible pathophysiological mechanism associated with TRD is inflammation [113].”
BackgroundNon-steroidal anti-inflammatory drugs and efficacy of antidepressants in major depressive disorder
Uher, R., Carver, S., Power, R. A., Mors, O., Maier, W., Rietschel, M., Hauser, J., Dernovsek, M. Z., Henigsberg, N., Souery, D., et al. (2012) · Psychological Medicine · doi:10.1017/s0033291712000190 · Cited by 45
The Extrinsic Coagulation Pathway: a Biomarker for Suicidal Behavior in Major Depressive Disorder
Yang, Y., Chen, J., Liu, C., Fang, L., Liu, Z., Guo, J., Cheng, K., Zhou, C., Zhan, Y., Melgiri, N. D., et al. (2016) · Scientific Reports · doi:10.1038/srep32882 · Cited by 44
Powell, T. R., McGuffin, P., D'Souza, U. M., Cohen-Woods, S., Hosang, G. M., Martin, C., Matthews, K., Day, R. K., Farmer, A. E., Tansey, K. E., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091076 · Cited by 45
Stewart, A. M., Roy, S., Wong, K., Gaikwad, S., Chung, K. M., & Kalueff, A. V. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.08.037 · Cited by 44
Rizvi, S. J., Donovan, M., Giacobbe, P., Placenza, F., Rotzinger, S., & Kennedy, S. H. (2011) · International Review of Psychiatry · doi:10.3109/09540261.2011.630993 · Cited by 42
Zhong, X., Xie, L., Yang, X., Liang, F., Yang, Y., Tong, J., Zhong, Y., Zhao, K., Tang, Y., & Yuan, C. (2020) · Molecular Medicine · doi:10.1186/s10020-020-00181-3 · Cited by 42
Porterfield, V. M., Gabella, K. M., Simmons, M. A., & Johnson, J. D. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.08.001 · Cited by 42
Felger, J. C., Alagbe, O., Pace, T. W. W., Woolwine, B. J., Hu, F., Raison, C. L., & Miller, A. H. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.02.015 · Cited by 41
“Activation of the innate immune system has been shown to produce behavioral alterations that are mediated in part by changes in monoamine metabolism and the hypothalamicpituitary-adrenal (HPA) axis (Dantzer et al. 2008; Miller et al. 2009).”
BackgroundSelf-citationIncreased IL-8 Concentrations in the Cerebrospinal Fluid of Patients with Unipolar Depression
Kuzior, H., Fiebich, B. L., Yousif, N. M., Saliba, S. W., Ziegler, C., Nickel, K., Maier, S. J., Süß, P., Runge, K., Matysik, M., et al. (2020) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2020.152196 · Cited by 41
Xu, Y., Liang, J., Sun, Y., Zhang, Y., Shan, F., Ge, J., & Xia, Q. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110108 · Cited by 41
Zavvari, F., Nahavandi, A., & Goudarzi, M. (2020) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2019.101711 · Cited by 38
Melinder, C., Hiyoshi, A., Fall, K., Halfvarson, J., & Montgomery, S. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-014315 · Cited by 40
Sharpley, A. L., Cooper, C. M., Williams, C., Godlewska, B. R., & Cowen, P. J. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4381-z · Cited by 39
Teyssier, J.-R., Ragot, S., Chauvet-Gélinier, J.-C., Trojak, B., & Bonin, B. (2011) · Psychiatry Research · doi:10.1016/j.psychres.2010.07.030 · Cited by 39
Godara, M., Silveira, S., Matthäus, H., Heim, C., Voelkle, M., Hecht, M., Binder, E. B., & Singer, T. (2021) · PLOS ONE · doi:10.1371/journal.pone.0256323 · Cited by 38
Neuro-, Cardio-, and Immunoplasticity: Effects of Early Adversity
Pakulak, E., Stevens, C., & Neville, H. (2018) · Annual Review of Psychology · doi:10.1146/annurev-psych-010416-044115 · Cited by 37
Druzhkova, T., Pochigaeva, K., Yakovlev, A., Kazimirova, E., Grishkina, M., Chepelev, A., Guekht, A., & Gulyaeva, N. (2019) · Metabolic Brain Disease · doi:10.1007/s11011-018-0367-3 · Cited by 37
Statins: Neurobiological underpinnings and mechanisms in mood disorders
Walker, A. J., Kim, Y., Borissiouk, I., Rehder, R., Dodd, S., Morris, G., Nierenberg, A. A., Maes, M., Fernandes, B. S., Dean, O. M., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.012 · Cited by 33
Cerebrospinal Fluid Levels of Interleukin-8 in Delirium, Dementia, and Cognitively Healthy Patients
Sajjad, M. U., Blennow, K., Knapskog, A. B., Idland, A.-V., Chaudhry, F. A., Wyller, T. B., Zetterberg, H., & Watne, L. O. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190941 · Cited by 34
Endocrine factors in key structural and intracellular changes in depression
Gold, P. W. (2021) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2021.01.003 · Cited by 35
Meta-analysis of molecular imaging of translocator protein in major depression
Eggerstorfer, B., Kim, J.-H., Cumming, P., Lanzenberger, R., & Gryglewski, G. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.981442 · Cited by 35
Attention to emotional information is associated with cytokine responses to psychological stress.
Maydych, V., Claus, M., Watzl, C., & Kleinsorge, T. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00687 · Cited by 33
Interaction mechanisms between major depressive disorder and non-alcoholic fatty liver disease
Shao, Q., Wu, Y., Ji, J., Xu, T., Yu, Q., Ma, C., Liao, X., Cheng, F., & Wang, X. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.711835 · Cited by 32
Song, B. M., Lee, J.-M., Choi, W., Youm, Y., Chu, S. H., Park, Y.-R., & Kim, H. C. (2015) · BMJ Open · doi:10.1136/bmjopen-2014-006429 · Cited by 33
Late-life depression symptom profiles are differentially associated with immunometabolic functioning
Vogelzangs, N., Comijs, H. C., Oude Voshaar, R. C., Stek, M. L., & Penninx, B. W. J. H. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.05.004 · Cited by 32
Lee, S., Oh, S. S., Jang, S.-I., & Park, E.-C. (2019) · Scientific Reports · doi:10.1038/s41598-018-36402-3 · Cited by 29
Chaiton, M., O’Loughlin, J., Karp, I., & Lambert, M. (2010) · International Journal of Behavioral Medicine · doi:10.1007/s12529-010-9078-9 · Cited by 29
Monocyte Chemoattractant Protein-1 Levels Are Associated with Major Depressive Disorder
Proma, M. A., Daria, S., Nahar, Z., Ashraful Islam, S. M., Bhuiyan, M. A., & Islam, M. R. (2022) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2021-0132 · Cited by 29
Meyer, J. D., Hayney, M. S., Coe, C. L., Ninos, C. L., & Barrett, B. P. (2019) · Journal of Sport and Exercise Psychology · doi:10.1123/jsep.2018-0214 · Cited by 29
Abnormal stress responsiveness and suicidal behavior: a risk phenotype
Steinberg, L. J., & Mann, J. J. (2020) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2020.100011 · Cited by 29
Jung, Y.-E., & Kang, K. Y. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104397 · Cited by 29
van Belkum, S. M., Bosker, F. J., Kortekaas, R., Beersma, D. G. M., & Schoevers, R. A. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.07.006 · Cited by 29
Trajectories of relationship stress and inflammatory processes in adolescence
Ehrlich, K. B., Miller, G. E., Rohleder, N., & Adam, E. K. (2016) · Development and Psychopathology · doi:10.1017/s0954579415000334 · Cited by 28
Genetic disposition to inflammation and response to antidepressants in major depressive disorder
Zwicker, A., Fabbri, C., Rietschel, M., Hauser, J., Mors, O., Maier, W., Zobel, A., Farmer, A., Aitchison, K. J., McGuffin, P., et al. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.08.011 · Cited by 28
Paroxetine suppresses recombinant human P2X7 responses
Dao-Ung, P., Skarratt, K. K., Fuller, S. J., & Stokes, L. (2015) · Purinergic Signalling · doi:10.1007/s11302-015-9467-2 · Cited by 29
Kronsten, V. T., & Shawcross, D. L. (2022) · Analytical Biochemistry · doi:10.1016/j.ab.2021.114437 · Cited by 27
de Menezes, S. T., de Figueiredo, R. C., Goulart, A. C., Nunes, M. A., M. Benseñor, I., Viana, M. C., & Barreto, S. M. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.10.046 · Cited by 25
Astrocytic TNFα regulates the behavioral response to antidepressants
Duseja, R., Heir, R., Lewitus, G. M., Altimimi, H. F., & Stellwagen, D. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.09.012 · Cited by 25
Gao, Z., Li, B., Guo, X., Bai, W., & Kou, C. (2023) · BMC Psychiatry · doi:10.1186/s12888-023-04760-6 · Cited by 22
Inflammatory markers and incident depression: evidence in a population-based prospective study
Shi, R., Gwee, X., Chua, D. Q., Tan, C. T., Yap, K. B., Larbi, A., Lu, Y., & Ng, T. P. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.105806 · Cited by 23
Nishi, D., Hashimoto, K., Noguchi, H., Kim, Y., & Matsuoka, Y. (2015) · Neuropsychobiology · doi:10.1159/000382021 · Cited by 23
Yrondi, A., Vaiva, G., Walter, M., D Amato, T., Bellivier, F., Bennabi, D., Bougerol, T., Camus, V., Doumy, O., Genty, J.-B., et al. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.12.055 · Cited by 21
Quest for biomarkers of treatment-resistant depression: Shifting the paradigm toward risk
Smith, D. F. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00057 · Cited by 22
Mechanisms and treatment of late-life depression
Alexopoulos, G. S. (2021) · Focus · doi:10.1176/appi.focus.19304 · Cited by 22
Teixeira, A. L., Martins, L. B., Berk, M., & Bauer, M. E. (2022) · Clinical Science · doi:10.1042/cs20211106 · Cited by 22
Increased Systemic Microbial Translocation Is Associated with Depression during Early Pregnancy
Zhou, Z., Guille, C., Ogunrinde, E., Liu, R., Luo, Z., Powell, A., & Jiang, W. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.11.009 · Cited by 20
“Dysregulation of the innate immune system is thought to be important in the etiology of major depression (Miller et al., 2009).”
Caes, L., Orchard, A., & Christie, D. (2017) · Healthcare · doi:10.3390/healthcare5040093 · Cited by 20
Feng, M., Crowley, N. A., Patel, A., Guo, Y., Bugni, S. E., & Luscher, B. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.03.003 · Cited by 20
Emotion-on-a-chip (EOC): Evolution of biochip technology to measure human emotion using body fluids
Lee, J.-H., Hwang, Y., Cheon, K.-A., & Jung, H.-I. (2012) · Medical Hypotheses · doi:10.1016/j.mehy.2012.09.002 · Cited by 20
Altered Levels of Salivary Cytokines in Patients with Major Depressive Disorder
Yui, S., Sasayama, D., Yamaguchi, M., & Washizuka, S. (2022) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2022.107390 · Cited by 16
Greaney, J. L., Saunders, E. F. H., & Alexander, L. M. (2022) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00643.2021 · Cited by 17
Peng, X., Brenner, L. A., Mathai, A. J., Cook, T. B., Fuchs, D., Postolache, N., Groer, M. W., Pandey, J. P., Mohyuddin, F., Giegling, I., et al. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.03.045 · Cited by 16
Prevalence and correlates of major depression in Granada, Spain: Results from the GranadΣp study
Porras-Segovia, A., Valmisa, E., Gutiérrez, B., Ruiz, I., Rodríguez-Barranco, M., & Cervilla, J. (2018) · International Journal of Social Psychiatry · doi:10.1177/0020764018771405 · Cited by 16
Cano-Ibáñez, N., Serra-Majem, L., Martín-Peláez, S., Martínez-González, M. Á., Salas-Salvadó, J., Corella Piquer, M. D., Lassale, C., Martínez Hernandez, J. A., Alonso-Gómez, Á. M., Wärnberg, J., et al. (2022) · British Journal of Nutrition · doi:10.1017/s0007114521004323 · Cited by 15
A longitudinal, randomized and controlled study of app-delivered mindfulness in the workplace
Emory University, & Mascaro, J. (2020) · Journal of Wellness · doi:10.18297/jwellness/vol2/iss1/4 · Cited by 12
“A large body of work supports the role of chronic, low-grade inflammation in fatigue [5658] and mood disorders [59].”
BackgroundKern, S., Skoog, I., Börjesson-Hanson, A., Blennow, K., Zetterberg, H., Östling, S., Kern, J., Gudmundsson, P., Marlow, T., Rosengren, L., et al. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.03.011 · Cited by 13
RetractedChild and Adolescent Psychiatry, U. O. H. S., Önen, Ö., Erkuran, H. Ö., Child and Adolescent Psychiatry, U. O. H. S., Bağ, Ö., Department of Social Pediatrics, U. O. H. S., Abacıgil, F., & Department of Public Health, A. A. M. U. F. O. M. (2021) · Psychiatry and Clinical Psychopharmacology · doi:10.5152/pcp.2021.21137 · Cited by 13
Study on the comorbid mechanisms of sarcopenia and late-life depression
Wu, J., Tang, J., Huang, D., Wang, Y., Zhou, E., Ru, Q., Xu, G., Chen, L., & Wu, Y. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115538 · Cited by 12
Vai, B., Mazza, M. G., Cazzetta, S., Calesella, F., Aggio, V., Lorenzi, C., Zanardi, R., Poletti, S., Colombo, C., & Benedetti, F. (2021) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2021.100254 · Cited by 13
Chapman, A., & Santos-Lozada, A. R. (2020) · SSM - Population Health · doi:10.1016/j.ssmph.2020.100663 · Cited by 11
Metadata
- Authors
- Miller, A. H., Maletic, V., & Raison, C. L.
- Affiliations
- Emory University (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 65
- Issue
- 9
- Pages
- 732-741
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2680424
- OpenAlex
- W1996454121
- Cited by
- 3,848
- References
- 121
- Citations by year
- 2026: 163 · 2025: 243 · 2024: 237 · 2023: 226 · 2022: 263 · 2021: 318 · 2020: 277 · 2019: 229 · 2018: 263 · 2017: 216 · 2016: 244 · 2015: 255 · 2014: 220 · 2013: 206 · 2012: 180
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Heart, Lung, and Blood Institute (R01HL073921)
- National Institute of Mental Health (R01MH083746, K23MH064619, T32MH020018, R01MH070553, K05MH069124)
- National Center for Research Resources (M01-RR00039, M01RR000039)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- major depressive disorder, inflammation, cytokines, inflammatory markers, neuroinflammation, neurotrophic support, glutamate release, oxidative stress, excitotoxicity, neuroendocrine function, neuroplasticity, psychosocial stress, NF-κB, sympathetic nervous system, antidepressant resistance, immune-targeted therapy, treatment response
- MeSH terms
- Animals, Anti-Inflammatory Agents, Basal Ganglia, Brain, Major Depressive Disorder, Depressive Disorder, Major, Humans, Inflammation, Neuronal Plasticity, Neurosecretory Systems, Stress, Psychological, Biomarkers, Cytokines, Neurotransmitter Agents
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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
