The DOI matches its Crossref record; 45 of the 48 references it cites were found in a registry or an index.
Peripheral Inflammation is Associated with Altered Substantia Nigra Activity and Psychomotor Slowing in Humans
Open accessAbstract
BackgroundSystemic infections commonly cause sickness symptoms including psychomotor retardation. Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain.MethodsWe used functional magnetic resonance brain imaging (fMRI) to investigate neural effects of peripheral inflammation following typhoid vaccination in 16 healthy men, using a double-blind, randomized, crossover-controlled design.ResultsVaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation. During a cognitive task, individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses. Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra.ConclusionsOur findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance, specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection. Systemic infections commonly cause sickness symptoms including psychomotor retardation. Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain. We used functional magnetic resonance brain imaging (fMRI) to investigate neural effects of peripheral inflammation following typhoid vaccination in 16 healthy men, using a double-blind, randomized, crossover-controlled design. Vaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation. During a cognitive task, individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses. Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra. Our findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance, specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection.
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
Figures
![Figure 4 Effect of peripheral inflammation on neural reactivity during low-grade visual stimulation task. (A) Mean BOLD signal change (+SEM) during checkerboard stimulus in all voxels probabilistically assigned to Brodmann areas 17 and 18 for vaccine and placebo conditions. There was no significant interaction between mean activation to visual stimulation and inflammatory state in either BA17 (p = .11) or BA18 (p = .34), confirming no effect of inflammation on neurovascular coupling. (B) Interaction between task performance and inflammatory state shows a highly significant change in BOLD signal within the left substantia nigra during performance of flashing checkerboard task (p = .002 after whole brain family-wise error [FWE] correction at p = .05). BA, Brodmann area; BOLD, blood oxygenation level-dependent; FWE, family-wise error.](/paper-figures/e5544e107a4548e884a3a9d6c344e8fb/peripheral-inflammation-is-associated-with-altered-substantia-nigra-activity-and-figure-4.jpg)
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 cited source says what the claim attributes to it.
In the citing paper
“typhoid vaccination has been associated with altered neural activity in the substantia nigra, a part of the basal ganglia that is involved in motor planning and reward seeking”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Brydon, Harrison, Walker, Steptoe, & Critchley, 2008
In the citing paper
“Brydon et al. (2008) examined Stroop performance after typhoid vaccination, and found that individuals with higher vaccine-induced IL-6 levels had significantly slower reaction times across both incongruent and congruent trials.”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Thus, inflammation did not impair inhibitory control, but rather led to an overall psychomotor slowing and/or decrease in motivation (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Studies across the endotoxin, typhoid vaccination, and IFN-α paradigms have consistently shown that exogenous stimulation of proinflammatory cytokines leads to reports of increased fatigue (Brydon et al., 2008; Capuron et al., 2002; Dowell et al., 2016; Eisenberger et al., 2010a; Grigoleit et al., 2011; Harrison et al., 2009; Moieni et al., 2015) and decreases in ratings of vigor (Dowell et al., 2”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Further, greater IL-6 following typhoid vaccination was associated with slower response times on all trials of a color-word Stroop task (both congruent and incongruent trials) (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Notably, increases in IL-6 and decreases in motor speed were both associated with altered activation patterns (enhanced activation) in the substantia nigra (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“This is exemplified by typhoid vaccine studies which can lead to increases in fatigue within 2–3 hours despite eliciting only mild, acute increases in inflammation (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Mild, short-term increases in inflammation are sufficient to cause somatic symptoms, particularly fatigue.”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“depression and fatigue are the main side effects of treatment with IFN-α (111, 112).”
From Cytokine Research in Depression: Principles, Challenges, and Open Questions (2019) · cites this paper as [111]
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
Dopamine, learning and motivation.
Wise, R. A. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1406 · Cited by 3,379 · cited 2×
“gonists that potentiate dopaminergic neurotransmission imrove the speed of motor responses in animals, whereas striatal opamine depletion and selective blockade of dopamine D1 or 2 receptors significantly impair performance on reaction time asks (13,16,17).”
Biological basis of the behavior of sick animals
Hart, B. L. (1988) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(88)80004-6 · Cited by 2,223
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365
Systemic infections and inflammation affect chronic neurodegeneration
Perry, V. H., Cunningham, C., & Holmes, C. (2007) · Nature Reviews Immunology · doi:10.1038/nri2015 · Cited by 1,027
Kim, W., Mohney, R. P., Wilson, B. C., Jeohn, G., Liu, B., & Hong, J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06309.2000 · Cited by 881
Optimized EPI for fMRI studies of the orbitofrontal cortex
Deichmann, R., Gottfried, J. A., Hutton, C., & Turner, R. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00073-9 · Cited by 821
Maes, M., Bosmans, E., De Jongh, R., Kenis, G., Vandoolaeghe, E., & Neels, H. (1997) · Cytokine · doi:10.1006/cyto.1997.0238 · Cited by 728
Gao, H., Jiang, J., Wilson, B. C., Zhang, W., Hong, J., & Liu, B. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00928.x · Cited by 690
Kim, Y. S., & Joh, T. H. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.40 · Cited by 655
Acute Systemic Inflammation Impairs Endothelium-Dependent Dilatation in Humans
Hingorani, A. D., Cross, J. M., Kharbanda, R. K., Mullen, M. J., Bhagat, K., Taylor, M., Donald, A. E., Palacios‐Callender, M., Griffin, G. E., Deanfield, J. E., et al. (2000) · Circulation · doi:10.1161/01.cir.102.9.994 · Cited by 605
Cited by
Sorted by citations
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848
“Both IFN-alpha and typhoid vaccination have been associated with psychomotor slowing and/or fatigue in association with changes in neuronal activity in the substantia nigra, putamen, and nucleus accumbens, as measured by functional magnetic resonance imaging (fMRI) and positron emission tomography (16,100).”
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.4 · Cited by 1,617
Visceral influences on brain and behavior
Critchley, H. D., & Harrison, N. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.008 · Cited by 1,177
“Animal studies indicate that sympathetic activation blunts cerebral blood flow responses to hypoxia, hypercapnia, and hypertension (López de Pablo et al., 1982; Busija, 1984).”
Self-citationImmune system to brain signaling: Neuropsychopharmacological implications
Capuron, L., & Miller, A. H. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.014 · Cited by 1,195
“…induce altered metabolic activity (as revealed by positron emission tomography) and blood flow (as measured by functional magnetic resonance imaging) in relevant basal ganglia nuclei including the nucleus accumbens, putamen, and substantia nigra (Capuron et al., 2007b; Brydon et al., 2008).”
BackgroundInfluentialInflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications
Felger, J. C., & Lotrich, F. E. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.060 · Cited by 1,180
“, 2010), and increased nigral activity that correlated with psychomotor slowing (Brydon et al., 2008).”
BackgroundInfluentialMicroglial priming in neurodegenerative disease
Perry, V. H., & Holmes, C. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.38 · Cited by 1,127
Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa
Dantzer, R. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2016 · Cited by 1,073
Haroon, E., Raison, C. L., & Miller, A. H. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.205 · Cited by 1,000
“In conjunction with IL-6 and IL-23, IL-1b is the most effective inducer of IL-17 expression in naive T cells in humans (Boissier et al, 2008).”
BackgroundInfluentialThe vascular depression hypothesis: mechanisms linking vascular disease with depression
Taylor, W. D., Aizenstein, H. J., & Alexopoulos, G. S. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.20 · Cited by 923
Miller, A. H., Haroon, E., Raison, C. L., & Felger, J. C. (2013) · Depression and Anxiety · doi:10.1002/da.22084 · Cited by 892
“[32] Increased neural activity in the substantia nigra was in turn correlated with increases in IL-6 as well as psychomotor slowing.[32] Taken together, the consistency of neuroimaging data across immune stimuli suggest that basal ganglia nuclei are a primary target of cytokine effects on the brain, leading to changes…”
BackgroundInfluentialHarrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., & Critchley, H. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.015 · Cited by 756
“Findings in the same group of participants are also reported elsewhere (19,16).”
Self-citationFelger, J. C., Li, Z., Haroon, E., Woolwine, B. J., Jung, M. Y., Hu, X., & Miller, A. H. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.168 · Cited by 620
Raison, C. L., Dantzer, R., Kelley, K. W., Lawson, M. A., Woolwine, B. J., Vogt, G., Spivey, J. R., Saito, K., & Miller, A. H. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.116 · Cited by 630
Bennett, J. M., Reeves, G., Billman, G. E., & Sturmberg, J. P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00316 · Cited by 531
“For example, sickness behavior or depression-like symptoms including negative mood, fatigue, and psychomotor slowing in otherwise healthy volunteers can be created via exposure to pro-inflammatory cytokines (1, 141, 142).”
BackgroundIs depression an inflammatory disorder?
Raison, C. L., & Miller, A. H. (2011) · Current Psychiatry Reports · doi:10.1007/s11920-011-0232-0 · Cited by 524
Calder, P. C., Bosco, N., Bourdet‐Sicard, R., Capuron, L., Delzenne, N. M., Dore, J. M., Franceschi, C., Lehtinen, M. J., Recker, T., Salvioli, S., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.09.001 · Cited by 524
“Similar findings were reported in healthy subjects subjected to an acute immune stimulus such as vaccination (Brydon et al., 2008; Eisenberger et al., 2010; Harrison et al., 2009).”
The neuroinflammatory hypothesis of delirium
Cerejeira, J., Firmino, H., Vaz‐Serra, A., & Mukaetova‐Ladinska, E. B. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0674-1 · Cited by 494
“More recently, a study using functional MRI documented that injection of peripheral LPS in healthy volunteers evoked a sustained systemic inflammatory reaction and psychomotor retardation in cognitive tasks and this correlated with enhanced activity in the left substantia nigra (SN) [21].”
BackgroundInflammation Effects on Motivation and Motor Activity: Role of Dopamine
Felger, J. C., & Treadway, M. T. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.143 · Cited by 474
“Numerous studies have reported increased circulating inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), their soluble receptors, and acute-phase reactants, such as C-reactive protein (CRP), in patients with MDD (Maes, 1999; Maes et al, 1992; Sluzewska, 1999).”
BackgroundInfluentialThe neurobiology of interoception in health and disease
Quadt, L., Critchley, H., & Garfinkel, S. N. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13915 · Cited by 488
Self-citationImaging the Role of Inflammation in Mood and Anxiety-related Disorders
Felger, J. C. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666171123201142 · Cited by 447
“Additionally, typhoid vaccination compared to saline has been shown to affect activity in the substantia nigra, including increased activation during a cognitive Stroop task and decreased activation in response to visual or novel stimuli, which correlated with both psychomotor slowing and increased peripheral blood co…”
BackgroundDepression in HIV Infected Patients: a Review
Nanni, M. G., Caruso, R., Mitchell, A. J., Meggiolaro, E., & Grassi, L. (2015) · Current Psychiatry Reports · doi:10.1007/s11920-014-0530-4 · Cited by 511
Rheumatoid arthritis and depression: an inflammatory perspective
Nerurkar, L., Siebert, S., McInnes, I. B., & Cavanagh, J. (2018) · The Lancet Psychiatry · doi:10.1016/s2215-0366(18)30255-4 · Cited by 426
Depression: an inflammatory illness?: Figure 1
Krishnadas, R., & Cavanagh, J. (2012) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2011-301779 · Cited by 392
“Areas that have been shown to be activated include the insula, an area thought to be important in body representation and subjective emotional experience, and the substantia nigra, that correlated with measures of fatigue and psychomotor slowing, findings that are consistent with the clinical findings of Capuron et al…”
ResultFelger, J. C., & Miller, A. H. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.09.003 · Cited by 413
“Sissolak G, Hoffbrand AV, Mehta AB, Ganeshaguru K. Effects of interferon-alpha (IFN) on the expression of interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colonystimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF) in acute myeloid leukemia (AML) blasts.”
BackgroundInfluentialCapuron, L., Pagnoni, G., Drake, D. F., Woolwine, B. J., Spivey, J. R., Crowe, R. J., Votaw, J. R., Goodman, M. M., & Miller, A. H. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.2094 · Cited by 382
“Data reported herein replicate previous findings using fMRI that inflammatory stimuli are associated with decreased basal ganglia activity involving hedonic reward circuitry, which correlated with behavioral alterations, including anhedonia, depression, and fatigue.(2,5,6) In addition, the present findings extend thes…”
BackgroundResultReview: Systemic inflammation andAlzheimer's disease
Holmes, C. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01307.x · Cited by 356
Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults
Marsland, A. L., Gianaros, P. J., Abramowitch, S. M., Manuck, S. B., & Hariri, A. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.04.016 · Cited by 348
Neural Origins of Human Sickness in Interoceptive Responses to Inflammation
Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., Dolan, R. J., & Critchley, H. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.007 · Cited by 345
“We have previously reported that inflammatory influences on lowlevel psychomotor responses with this task are modulated via an action on the substantia nigra (26).”
InfluentialSelf-citationDepression and immunity: A role for T cells?
Miller, A. H. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.09.009 · Cited by 345
“…lead to a host of behavioral changes that overlap with those seen in depressed patients including depressed mood, anxiety, anorexia, fatigue, psychomotor retardation, impaired sleep and cognitive dysfunction (Brydon et al., 2008; Miller et al., 2009; Reichenberg et al., 2001; Wright et al., 2005).”
BackgroundBrain morphology links systemic inflammation to cognitive function in midlife adults
Marsland, A. L., Gianaros, P. J., Kuan, D. C.-H., Sheu, L. K., Krajina, K., & Manuck, S. B. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.03.015 · Cited by 321
Psychophysiology of neural, cognitive and affective integration: fMRI and autonomic indicants
Critchley, H. D. (2009) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2009.01.012 · Cited by 323
Self-citationAn fMRI study of cytokine-induced depressed mood and social pain: The role of sex differences
Eisenberger, N. I., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.04.040 · Cited by 313
“Rather, the few experimental studies of cytokine-induced changes in neural activity have focused primarily on cognitive, as opposed to social or affective changes (Brydon et al., 2008; Capuron et al., 2005).”
BackgroundDopamine, Immunity, and Disease
Channer, B., Matt, S. M., Nickoloff-Bybel, E. A., Pappa, V., Agarwal, Y., Wickman, J. R., & Gaskill, P. J. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000618 · Cited by 328
Cytokine Research in Depression: Principles, Challenges, and Open Questions
Himmerich, H., Patsalos, O., Lichtblau, N., Ibrahim, M. A. A., & Dalton, B. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00030 · Cited by 313
Zunszain, P. A., Hepgul, N., & Pariante, C. M. (2012) · Current topics in behavioral neurosciences · doi:10.1007/7854_2012_211 · Cited by 327
Iob, E., Kirschbaum, C., & Steptoe, A. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0501-6 · Cited by 305
Self-citationHaroon, E., Daguanno, A. W., Woolwine, B. J., Goldsmith, D. R., Baer, W. M., Wommack, E. C., Felger, J. C., & Miller, A. H. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.05.026 · Cited by 291
“Administration of inflammatory cytokines also has been associated with the development of depressive symptoms (Brydon et al., 2008; Capuron et al., 2002a; Eisenberger et al., 2010), and blockade of inflammatory mediators has been shown to improve depressive symptoms in patients with autoimmune and inflammatory disorde…”
BackgroundHiles, S. A., Baker, A. L., de Malmanche, T., & Attia, J. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.06.001 · Cited by 274
“, 2004), and cognitive problems and psychomotor slowing (Brydon et al., 2008; Reichenberg et al., 2001).”
BackgroundImmune aging, dysmetabolism, and inflammation in neurological diseases
Deleidi, M., Jäggle, M., & Rubino, G. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00172 · Cited by 260
“Systemic inflammation promotes the activation of brain immune cells in humans as well as in non-human primates (Brydon et al., 2008; Harrison et al., 2009; Hannestad et al., 2012) and can prime neurons and immune cells in the brain increasing the risk of developing neurological disorders (Deleidi…”
BackgroundMeyer, U., Schwarz, M., & Müller, N. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.06.003 · Cited by 262
“, 2008) and psychomotor retardation (Brydon et al., 2008).”
BackgroundThe evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)
Raison, C. L., & Miller, A. H. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.2 · Cited by 253
Haroon, E., Fleischer, C. C., Felger, J. C., Chen, X., Woolwine, B. J., Patel, T., Hu, X. P., & Miller, A. H. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.206 · Cited by 250
Nutrition for the ageing brain: Towards evidence for an optimal diet
Vauzour, D., Camprubi-Robles, M., Miquel-Kergoat, S., Andres-Lacueva, C., Bánáti, D., Barberger-Gateau, P., Bowman, G. L., Caberlotto, L., Clarke, R., Hogervorst, E., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.010 · Cited by 241
Affective disturbance in rheumatoid arthritis: Psychological and disease-related pathways
Sturgeon, J. A., Finan, P. H., & Zautra, A. J. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.112 · Cited by 232
Anand, D., Colpo, G. D., Zeni, G., Zeni, C. P., & Teixeira, A. L. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00228 · Cited by 221
“Accordingly, cytokines can influence cognitive processes, including reaction time and working memory (29), that can be impaired in ADHD.”
BackgroundInflammation and the dimensions of depression: A review
Majd, M., Saunders, E. F. H., & Engeland, C. G. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100800 · Cited by 229
Inflammation-Related Functional and Structural Dysconnectivity as a Pathway to Psychopathology
Goldsmith, D. R., Bekhbat, M., Mehta, N. D., & Felger, J. C. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.11.003 · Cited by 229
“In adults, IL-6 partially mediated relationships between childhood abuse and lower amygdala-vmPFC rsFC (105), and an inflammatory cytokine composite related to low salience, default mode network (DMN), and central executive inter-network rsFC in association with sub-clinical PTSD symptoms in stress-exposed firefighter…”
InfluentialFelger, J. C., Mun, J., Kimmel, H. L., Nye, J. A., Drake, D. F., Hernandez, C. R., Freeman, A. A., Rye, D. B., Goodman, M. M., Howell, L. L., et al. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.115 · Cited by 214
“In addition, typhoid vaccination has been shown to alter activity in the substantia nigra in relation to psychomotor slowing (Brydon et al, 2008).”
BackgroundAntidepressant therapies inhibit inflammation and microglial M1-polarization
Kalkman, H. O., & Feuerbach, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.001 · Cited by 212
Schedlowski, M., Engler, H., & Grigoleit, J.-S. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.09.015 · Cited by 195
Smith, K. J., Au, B., Ollis, L., & Schmitz, N. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.12.005 · Cited by 197
“Furthermore, there is evidence that inflammation may be linked primarily with somatic symptoms linked with depression (Duivis et al., 2013) such as hypersomnia (Irwin et al., 2016), adiposity (Shelton and Miller, 2010) or psychomotor slowing (Brydon et al., 2008).”
BackgroundThe Neurobiology of Depression: an Integrated Overview from Biological Theories to Clinical Evidence
Ferrari, F., & Villa, R. F. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0032-y · Cited by 198
Krogh, J., Benros, M. E., Jørgensen, M. B., Vesterager, L., Elfving, B., & Nordentoft, M. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.08.014 · Cited by 185
Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions
Miller, B. J., & Goldsmith, D. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.211 · Cited by 182
“…2012), neural activity in ventral striatal regions is altered following administration of several inflammatory stimuli including IFN-α, typhoid vaccination, and endotoxin in psychiatrically healthy individuals (Brydon et al, 2008; Capuron et al, 2012; Eisenberger et al, 2010; Harrison et al, 2015).”
BackgroundCastanon, N., Luheshi, G. N., & Layé, S. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00229 · Cited by 189
Felger, J. C., Li, L., Marvar, P. J., Woolwine, B. J., Harrison, D. G., Raison, C. L., & Miller, A. H. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.10.010 · Cited by 176
“Similarly, lipopolysaccharide (LPS) and typhoid vaccination have been shown to have effects on basal ganglia activity (Brydon et al. 2008; Eisenberger et al. 2010), including decreased ventral striatal activation to a reward task (Eisenberger et al. 2010), suggesting that the effects on basal…”
Parrott, J. M., Redus, L., Santana-Coelho, D., Morales, J., Gao, X., & O'Connor, J. C. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.200 · Cited by 174
Dooley, L. N., Kuhlman, K. R., Robles, T. F., Eisenberger, N. I., Craske, M. G., & Bower, J. E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.006 · Cited by 176
A critical review of human endotoxin administration as an experimental paradigm of depression.
DellaGioia, N., & Hannestad, J. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.07.014 · Cited by 175
“, 2007), and in subjects who received a typhoid vaccine, psychomotor slowing correlated with activity in the substantia nigra and IL-6 levels (Brydon et al., 2008).”
BackgroundRaison, C. L., Lowry, C. A., & Rook, G. A. W. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.161 · Cited by 169
“In addition to these correlative data, both immediate and longterm administration of proinflammatory cytokines (or substances that induce these cytokines) cause behavioral symptoms that overlap with those found in MDD and respond to standard antidepressant therapy.(86-91) Consistent with evidence that proinflammatory…”
The role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder
Woelfer, M., Kasties, V., Kahlfuss, S., & Walter, M. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.03.034 · Cited by 171
COVID-19 vaccination for people with severe mental illness: why, what, and how?
Mazereel, V., Assche, K. V., Detraux, J., & Binder, M. D. (2021) · The Lancet Psychiatry · doi:10.1016/s2215-0366(20)30564-2 · Cited by 181
Maes, M., Ruckoanich, P., Chang, Y. S., Mahanonda, N., & Berk, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.06.008 · Cited by 169
“In humans, systemic inflammation through typhoid vaccination causes higher levels of circulating IL-6 levels that are associated with prolonged reaction times and increased evoked neural activity within substantia nigra (Brydon et al., 2008).”
BackgroundInfluentialKraynak, T. E., Marsland, A. L., Wager, T. D., & Gianaros, P. J. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.07.013 · Cited by 165
Inflammation Models of Depression in Rodents: Relevance to Psychotropic Drug Discovery
Remus, J. L., & Dantzer, R. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw028 · Cited by 170
“The reduction in mood is correlated with plasma IL-6 levels (Brydon et al., 2008; Eisenberger et al., 2009) as is fatigue (Brydon et al.”
BackgroundCapuron, L., Fornwalt, F. B., Knight, B. T., Harvey, P. D., Ninan, P. T., & Miller, A. H. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.02.017 · Cited by 164
“…IL-6] or agents (e.g., lipopolysaccharide or typhoid vaccination) that stimulate an innate immune response have been found to induce depressive-like behaviors in laboratory animals and humans (Brydon et al., 2008; Dantzer et al., 2008; Raison et al., 2006; Reichenberg et al., 2001; Yirmiya, 1996).”
Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus
Soczynska, J. K., Kennedy, S. H., Woldeyohannes, H. O., Liauw, S. S. L., Alsuwaidan, M. T., Yim, C. Y., & McIntyre, R. S. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-010-8140-8 · Cited by 167
“For example, healthy males subjected to a typhoid vaccination show markedly abnormal neural reactivity within the sub- stantia nigra which was associated with psychomotor slowing (Brydon et al. 2008).”
Morris, G., Berk, M., Gałecki, P., Walder, K. R., & Maes, M. H. J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9090-9 · Cited by 163
“kines) has been demonstrated to produce similar responses in the basal ganglia, indicating that administration of IFNα and other inflammatory inputs yield similar effects [277, 278].”
BackgroundNeuropsychiatric Comorbidity in Obesity: Role of Inflammatory Processes
Castanon, N., Lasselin, J., & Capuron, L. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00074 · Cited by 168
Guo, P., Benito-Ballesteros, Á., Yeung, S. P., Liu, R., Saha, A., Curtis, L., Kaşer, M., Haggard, M. P., & Cheke, L. G. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.804937 · Cited by 170
“The patient-created term “Long COVID” has increasingly been used as an umbrella term to describe this highly heterogeneous condition (Callard and Perego, 2021).”
BackgroundHaroon, E., Woolwine, B. J., Chen, X., Pace, T. W., Parekh, S., Spivey, J. R., Hu, X. P., & Miller, A. H. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.25 · Cited by 154
“In addition, healthy volunteers exposed to typhoid vaccination (compared with placebo) showed altered activation in the substantia nigra that was associated with reduced psychomotor speed and increased peripheral blood interleukin-6 (Brydon et al, 2008).”
BackgroundTherapeutic Implications of Brain–Immune Interactions: Treatment in Translation
Miller, A. H., Haroon, E., & Felger, J. C. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.167 · Cited by 152
Oades, R. D., Dauvermann, M. R., Schimmelmann, B. G., Schwarz, M. J., & Myint, A.-M. (2010) · Behavioral and Brain Functions · doi:10.1186/1744-9081-6-29 · Cited by 151
“Potentially relevant to ADHD, for example, is that IL-2 can modulate the development of nigrostriatal and mesolimbic DA systems [70], enhance NA utilization [71], and like IL-6 influence reaction times and working memory performance [72,73].”
Human sickness behavior: Ultimate and proximate explanations
Shattuck, E. C., & Muehlenbein, M. P. (2015) · American Journal of Physical Anthropology · doi:10.1002/ajpa.22698 · Cited by 154
Goldsmith, D. R., Haroon, E., Woolwine, B. J., Jung, M. Y., Wommack, E. C., Harvey, P. D., Treadway, M. T., Felger, J. C., & Miller, A. H. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.03.025 · Cited by 150
“Similarly, healthy individuals given typhoid vaccination showed increased activity in the basal ganglia using fMRI, which was associated with both increases in peripheral blood IL-6 and psychomotor slowing (Brydon et al., 2008).”
BackgroundMethodResultInfluentialChu, A. L., Štochl, J., Lewis, G., Zammit, S., Jones, P. B., & Khandaker, G. M. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.11.007 · Cited by 136
“Similarly, immuno-activation in animals and healthy volunteers leads to fatigue, psychomotor retardation and anhedonia, which are typical somatic symptoms according to ICD-10 diagnostic criteria for depressive episode (Brydon et al., 2008; Capuron et al., 2012; Eisenberger et al., 2010; Harrison et al., 2009, 2015).”
Ghrelin's Roles in Stress, Mood, and Anxiety Regulation
Chuang, J.-C., & Zigman, J. M. (2010) · International Journal of Peptides · doi:10.1155/2010/460549 · Cited by 144
“In addition, several studies have shown that administration of cytokine or cytokine inducers such as LPS or vaccine can lead to the development of depressive symptoms, while antiinflammatory therapy generates antidepressantlike effects [52–54].”
BackgroundHarrison, N. A., Cooper, E., Dowell, N. G., Keramida, G., Voon, V., Critchley, H. D., & Cercignani, M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.09.023 · Cited by 129
“The Salmonella typhi vaccine experimental model of inflammation induces a low-grade inflammatory response associated with an approximately threefold increase in peripheral IL-6 levels peaking 3–4 hours after vaccination (16).”
Self-citationMolecular aspects of depression: A review from neurobiology to treatment
Boas, G. R. V., de Lacerda, R. B., Paes, M. M., Gubert, P., Almeida, W. L. D. C., Rescia, V. C., Galdino, P. M., de Carvalho, A. A. V., & Oesterreich, S. A. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.02.024 · Cited by 140
Mapping inflammation onto mood: inflammatory mediators of anhedonia
Swardfager, W., Rosenblat, J. D., Benlamri, M., & McIntyre, R. S. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.02.017 · Cited by 125
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126
Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications
Lucido, M. J., Bekhbat, M., Goldsmith, D. R., Treadway, M. T., Haroon, E., Felger, J. C., & Miller, A. H. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000043 · Cited by 133
“Increases in IL6 after typhoid vaccination have also been correlated with slowed reaction times (Brydon et al., 2008), suggesting that cytokine-induced changes in the basal ganglia can contribute to both motivational deficits and psychomotor retardation.”
BackgroundResultVanElzakker, M. B., Brumfield, S. A., & Mejia, P. S. L. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2018.01033 · Cited by 125
Systemic Inflammation Mediates Age-Related Cognitive Deficits
Lin, T., Liu, G. A., Perez, E., Rainer, R. D., Febo, M., Cruz-Almeida, Y., & Ebner, N. C. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00236 · Cited by 138
“, typhoid vaccination) consistently hindered reaction times among young participants (Brydon et al., 2008).”
BackgroundInfluentialFatigue in chronic liver disease: New insights and therapeutic approaches
Swain, M. G., & Jones, D. E. (2018) · Liver International · doi:10.1111/liv.13919 · Cited by 125
When grief heats up: Pro-inflammatory cytokines predict regional brain activation
O'Connor, M.-F., Irwin, M. R., & Wellisch, D. K. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.05.049 · Cited by 123
“A few studies have investigated the relationship between systemic inflammation and regional brain activation (Brydon et al., 2008; Capuron et al., 2005; Rocca et al., 2007).”
Harrison, N. A., Doeller, C. F., Voon, V., Burgess, N., & Critchley, H. D. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.01.005 · Cited by 118
“We also previously reported psychomotor slowing after typhoid vaccination (53).”
Self-citationRaison, C. L., Rye, D. B., Woolwine, B. J., Vogt, G. J., Bautista, B. M., Spivey, J. R., & Miller, A. H. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.019 · Cited by 116
A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase
Davies, Christmas, D. M., & Potokar, J. P. (2011) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s17573 · Cited by 121
“30 Provoking an acute inflammatory response in healthy humans, for example via injection of endotoxin, 6,7 IL-6, 36 or IFN-b , 37 also produces symptoms similar to those seen in depression (such as fatigue, lack of motivation, anorexia, poor sleep).”
Feeling hangry? When hunger is conceptualized as emotion.
MacCormack, J. K., & Lindquist, K. A. (2018) · Emotion · doi:10.1037/emo0000422 · Cited by 125
The role of dopamine in inflammation-associated depression: mechanisms and therapeutic implications
Felger, J. C. (2016) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2016_13 · Cited by 115
Glucose Metabolism in the Insula and Cingulate Is Affected by Systemic Inflammation in Humans
Hannestad, J., Subramanyam, K., DellaGioia, N., Planeta-Wilson, B., Weinzimmer, D., Pittman, B., & Carson, R. E. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.111.097014 · Cited by 113
“Other regions include the nucleus accumbens and putamen in interferon-a–induced fatigue (15), the substantia nigra in typhoid-vaccine–induced cognitive impairment (16), and the ventral striatum in response to monetary reward cues when subjects received endotoxin (17).”
BackgroundThe role of resilience in the clinical management of chronic pain
Hassett, A. L., & Finan, P. H. (2016) · Current Pain and Headache Reports · doi:10.1007/s11916-016-0567-7 · Cited by 107
Inflammation, Self-Regulation, and Health: An Immunologic Model of Self-Regulatory Failure
Shields, G. S., Moons, W. G., & Slavich, G. M. (2017) · Perspectives on Psychological Science · doi:10.1177/1745691616689091 · Cited by 121
“It will thus be important for future studies to examine the effects of inflammatory challenges that do not influence cortisol (e.g., typhoid vaccination; Brydon et al., 2008).”
Parrott, J. M., Redus, L., & O’Connor, J. C. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0590-y · Cited by 112
“unteers induces transient depression-associated symptoms that parallel the appearance of pro-inflammatory cytokines [3–6], whereas direct administration of proinflammatory cytokines in preclinical models recapitulates inflammation-associated depressive-like behaviors [7–10].”
BackgroundRosano, C., Marsland, A. L., & Gianaros, P. J. (2012) · Europe PMC (PubMed Central) · Cited by 111
Yin, L., Xu, X., Chen, G., Mehta, N. D., Haroon, E., Miller, A. H., Luo, Y., Li, Z., & Felger, J. C. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.05.011 · Cited by 113
Goldsmith, D. R., & Rapaport, M. H. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00046 · Cited by 115
Lasselin, J., Lekander, M., Axelsson, J., & Karshikoff, B. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.005 · Cited by 106
Metadata
- Authors
- Brydon, L., Harrison, N. A., Walker, C., Steptoe, A., & Critchley, H. D.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- Brighton and Sussex Medical School (GB)
- Corresponding author
- Brydon, Lena
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 63
- Issue
- 11
- Pages
- 1022-1029
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2885493
- OpenAlex
- W2059416963
- Cited by
- 381
- References
- 48
- Citations by year
- 2026: 5 · 2025: 20 · 2024: 23 · 2023: 22 · 2022: 16 · 2021: 41 · 2020: 25 · 2019: 20 · 2018: 26 · 2017: 15 · 2016: 35 · 2015: 26 · 2014: 17 · 2013: 19 · 2012: 25
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biological Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- peripheral inflammation, substantia nigra, psychomotor retardation, typhoid vaccination, interleukin-6, sickness behavior, neuroinflammation, dopaminergic midbrain, reaction time, neurovascular coupling, systemic infection, cytokines
- MeSH terms
- Adolescent, Adult, Brain Mapping, Double-Blind Method, Humans, Image Processing, Computer-Assisted, Inflammation, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Photic Stimulation, Psychomotor Performance, Reaction Time, Substantia Nigra, Typhoid Fever, Vaccination, Interleukin-6, Cross-Over Studies, Motor Skills Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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
